This study investigated water samples collected from the surface water and groundwater in Wuhan City,Hubei Province,China in different stages of the outbreak of the coronavirus disease 2019(hereinafter referred to as ...This study investigated water samples collected from the surface water and groundwater in Wuhan City,Hubei Province,China in different stages of the outbreak of the coronavirus disease 2019(hereinafter referred to as COVID-19)in the city,aiming to determine the distribution characteristics of antiviral drugs in the city’s waters.The results are as follows.The main hydrochemical type of surface water and groundwater in Wuhan was Ca-HCO3.The major chemical components in the groundwater had higher concentrations and spatial variability than those in the surface water.Two antiviral drugs and two glucocorticoids were detected in the surface water,groundwater,and sewage during the COVID-19 outbreak.Among them,chloroquine phosphate and cortisone had higher detection rates of 32.26%and 25.80%,respectively in all samples.The concentrations of residual drugs in East Lake were higher than those in other waters.The main drug detected in the waters in the later stage of the COVID-19 outbreak in Wuhan was chloroquine phosphate,whose detection rates in the surface water and the groundwater were 53.85%and 28.57%,respectively.Moreover,the detection rate and concentration of chloroquine phosphate were higher in East Lake than in Huangjia Lake.The groundwater containing chloroquine phosphate was mainly distributed along the river areas where the groundwater was highly vulnerable.The residual drugs in the surface water and the groundwater had lower concentrations in the late stage of the COVID-19 outbreak than in the middle of the outbreak,and they have not yet caused any negative impacts on the ecological environment.展开更多
Background:To compare the efficacy and safety of Chinese herbal medicine combined with nucleoside antiviral drugs and nucleoside antiviral drugs alone in treating recurrent genital herpes.Methods:PubMed,Embase,Web of ...Background:To compare the efficacy and safety of Chinese herbal medicine combined with nucleoside antiviral drugs and nucleoside antiviral drugs alone in treating recurrent genital herpes.Methods:PubMed,Embase,Web of Science,Cochrane Library,Chinese Biomedical Literature Database,China National Knowledge Internet,VIP Database,and Wanfang Data were searched from inception to April 2021.Randomized controlled trials on the efficacy and safety of oral Chinese herbal medicine combined with nucleoside antiviral drugs for recurrent genital herpes were collected.All included trials were independently assessed by two reviewers with the Cochrane risk-of-bias tool,and a meta-analysis was conducted using Review Manager 5.4.Results:Compared with the use of nucleoside antiviral drugs alone,combination therapy with oral Chinese herbal medicine plus nucleoside antiviral drugs effectively reduced the herpes recurrence rate after the end of treatment(3 months:P=0.0002;6 months:P<0.00001;1 year:P<0.00001)and the number of recurrences each year(P<0.00001),improved the recurrent Genital Herpes Quality of Life Questionnaire score(P<0.00001),and regulated the levels of interferon-γ,interleukin-2,tumor necrosis factor-α,and T lymphocyte subsets in the peripheral blood,and the difference was statistically significant.Different subgroups reported mixed results with respect to the efficacy in the short term.The incidence of adverse reactions and the time of symptom disappearance between the two groups were not significantly different.Conclusion:Chinese herbal medicine combined with nucleoside antiviral drugs can effectively reduce the recurrence rate of recurrent genital herpes,improve the patient’s quality of life and enhance the body’s immunity.Considering the possible risk of publication bias,more high-quality randomized controlled trials are still needed to verify the conclusions of this article.展开更多
We performed density functional theory (DFT) calculations for ribonucleotides and active triphosphate metabolites of candidate drugs against Coronavirus disease 2019 (Covid-19). Frontier orbitals (highest occupied mol...We performed density functional theory (DFT) calculations for ribonucleotides and active triphosphate metabolites of candidate drugs against Coronavirus disease 2019 (Covid-19). Frontier orbitals (highest occupied molecular orbital and lowest unoccupied molecular</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">orbital) at optimized structure of each molecule were obtained. T-705RTP (active triphosphate metabolite of favipiravir) and cytidine triphosphate (CTP) have similar shapes of frontier orbitals. We also obtained similar shapes of frontier orbitals among dihydroxy GS-441524 triphosphate (GS-441524 is an active triphosphate metabolite of remdesivir) and adenosine triphosphate (ATP). From a theoretical </span><span style="font-family:Verdana;">viewpoint, we suggest T-705RTP is a CTP analogue and dihydroxy GS-441524</span><span style="font-family:Verdana;"> triphosphate is an</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">ATP analogue.展开更多
SARS-CoV-2 causes the pandemic of COVID-19 and no effective drugs for this disease are available thus far.Due to the high infectivity and pathogenicity of this virus,all studies on the live virus are strictly confined...SARS-CoV-2 causes the pandemic of COVID-19 and no effective drugs for this disease are available thus far.Due to the high infectivity and pathogenicity of this virus,all studies on the live virus are strictly confined in the biosafety level 3(BSL3)laboratory but this would hinder the basic research and antiviral drug development of SARS-CoV-2 because the BSL3 facility is not commonly available and the work in the containment is costly and laborious.In this study,we constructed a reverse genetics system of SARS-CoV-2 by assembling the viral cDNA in a bacterial artificial chromosome(BAC)vector with deletion of the spike(S)gene.Transfection of the cDNA into cells results in the production of an RNA replicon that keeps the capability of genome or subgenome replication but is deficient in virion assembly and infection due to the absence of S protein.Therefore,such a replicon system is not infectious and can be used in ordinary biological laboratories.We confirmed the efficient replication of the replicon by demonstrating the expression of the subgenomic RNAs which have similar profiles to the wild-type virus.By mutational analysis of nsp12 and nsp14,we showed that the RNA polymerase,exonuclease,and cap N7 methyltransferase play essential roles in genome replication and sgRNA production.We also created a SARS-CoV-2 replicon carrying a luciferase reporter gene and this system was validated by the inhibition assays with known anti-SARS-CoV-2 inhibitors.Thus,such a one-plasmid system is biosafe and convenient to use,which will benefit both fundamental research and development of antiviral drugs.展开更多
Due to the large-scale spread of COVID-19,which has a significant impact on human health and social economy,developing effective antiviral drugs for COVID-19 is vital to saving human lives.Various biomedical associati...Due to the large-scale spread of COVID-19,which has a significant impact on human health and social economy,developing effective antiviral drugs for COVID-19 is vital to saving human lives.Various biomedical associations,e.g.,drug-virus and viral protein-host protein interactions,can be used for building biomedical knowledge graphs.Based on these sources,large-scale knowledge reasoning algorithms can be used to predict new links between antiviral drugs and viruses.To utilize the various heterogeneous biomedical associations,we proposed a fusion strategy to integrate the results of two tensor decomposition-based models(i.e.,CP-N3 and Compl Ex-N3).Sufficient experiments indicated that our method obtained high performance(MRR=0.2328).Compared with CP-N3,the mean reciprocal rank(MRR)is increased by 3.3%and compared with Compl Ex-N3,the MRR is increased by 3.5%.Meanwhile,we explored the relationship between the performance and relationship types,which indicated that there is a negative correlation(PCC=0.446,P-value=2.26 e-194)between the performance of triples predicted by our method and edge betweenness.展开更多
liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especial...liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.展开更多
Since direct-acting antiviral agents(DAAs)have been introduced into hepatitis C virus treatment,the sustained viral response(SVR)rate has significantly increased to more than 95%.Scientific evidence supports the idea ...Since direct-acting antiviral agents(DAAs)have been introduced into hepatitis C virus treatment,the sustained viral response(SVR)rate has significantly increased to more than 95%.Scientific evidence supports the idea that SVR after interferon therapy has beneficial effects related to cirrhosis progression,resulting in a reduction in the incidence of hepatocellular carcinoma(HCC).However,a significant debate exists related to DAA impact on HCC development.We reviewed the current literature highlighting the controversial data related to DAA association with de novo HCC occurrence or recurrence and possible pathophysiology of HCC related to DAAs.After a review of the published literature,we believe that the current evidence does not confirm or repudiate a higher rate of de novo HCC occurrence or recurrence related to DAA therapy.More trials are needed to determine if there is an association between HCC occurrence or recurrence and DAA or if it is related to preexisting liver cirrhosis.展开更多
Hepatitis B virus (HBV)-related liver disease is the leading indication for liver transplantation (LT) in Asia,especially in China.With the introduction of hepatitis B immunoglobulin (HBIG) and oral antiviral drugs,th...Hepatitis B virus (HBV)-related liver disease is the leading indication for liver transplantation (LT) in Asia,especially in China.With the introduction of hepatitis B immunoglobulin (HBIG) and oral antiviral drugs,the recurrent HBV infection rate after LT has been evidently reduced.However,complete eradication of recurrent HBV infection after LT is almost impossible.Recurrent graft infection may lead to rapid disease progression and is a frequent cause of death within the fi rst year after LT.At present,the availability of new oral medications,especially nucleoside or nucleotide analogues such as adefovir dipivoxil,entecavir and tenofovir disoproxil fumarate,further strengthens our ability to treat recurrent HBV infection after LT.Moreover,since combined treatment with HBIG and antiviral agents after liver re-transplantation may play an important role in improving the prognosis of recurrent HBV infection,irreversible graft dysfunction secondary to recurrent HBV infection in spite of oral medications should no longer be considered an absolute contraindication for liver re-transplantation.Published reviews focusing on the therapeutic strategies for recurrent HBV infection after LT are very limited.In this article,the current therapeutic strategies for recurrent HBV infection after LT and evolving new trends are reviewed to guide clinical doctors to choose an optimal treatment plan in different clinical settings.展开更多
Hepatitis B virus(HBV) recurrence after liver transplantation(LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication...Hepatitis B virus(HBV) recurrence after liver transplantation(LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication, early reports described in details recurrence and reactivation of HBV in liver transplant recipients. The evidence of a possible, severe, clinical evolution of HBV reappearance in a significant percentage of these patients, allowed to consider,for some years, HBV positivity a contraindication for LT. Moving from the old to the new millennium this picture has changed dramatically. Several studies contributed to establish efficient prophylactic protocols for HBV recurrence and with the advent of more potent anti-viral drugs an increased control of infection was achieved in transplanted patients as well as in the general immunecompetent HBV population. Success obtained in the last decade led some authors to the conclusion that HBV is now to consider just as a "mere nuisance".However, with regard to HBV and LT, outstanding issues are still on the table:(1)A standard HBV prophylaxis protocol after transplant has not yet been clearly defined;(2) The evidence of HBV resistant strains to the most potent antiviral agents is claiming for a new generation of drugs;and(3) The possibility of prophylaxis withdrawal in some patients has been demonstrated, but reliable methods for their selection are still lacking. The evolution of LT for HBV is examined in detail in this review together with the description of the strategies adopted to prevent HBV recurrence and their pros and cons.展开更多
Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread worldwide.Effective treatments against COVID-19 remain urgently in need although vaccination signific...Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread worldwide.Effective treatments against COVID-19 remain urgently in need although vaccination significantly reduces the incidence,hospitalization,and mortality.At present,antiviral drugs including Nirmatrelvir/Ritonavir(Paxlovid^(TM)),Remdesivir,and Molnupiravir have been authorized to treat COVID-19 and become more globally available.On the other hand,traditional Chinese medicine(TCM)has been used for the treatment of epidemic diseases for a long history.Currently,various TCM formulae against COVID-19 such as Qingfei Paidu decoction,Xuanfei Baidu granule,Huashi Baidu granule,Jinhua Qinggan granule,Lianhua Qingwen capsule,and Xuebijing injection have been widely used in clinical practice in China,which may cause potential herb-drug interactions(HDIs)in patients under treatment with antiviral drugs and affect the efficacy and safety of medicines.However,information on potential HDIs between the above anti-COVID-19 drugs and TCM formulae is lacking,and thus this work seeks to summarize and highlight potential HDIs between antiviral drugs and TCM formulae against COVID-19,and especially pharmacokinetic HDIs mediated by metabolizing enzymes and/or transporters.These well-characterized HDIs could provide useful information on clinical concomitant medicine use to maximize clinical outcomes and minimize adverse and toxic effects.展开更多
BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have...BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine learning algorithm(random forest).Coinfection with HBV(including patients with on-treatment reactivation of HBV infection)or HIV,extrahepatic manifestations,and renal failure did not significantly affect the treatment efficacy.CONCLUSION In patients with advanced liver disease,individualized therapy(testing for resistance-associated variants and response-guided treatment)should be considered to maximize the chance of achieving SVR.展开更多
The pandemic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has garnered the attention of scientists worldwide in the search for an effective treatment while also focusing on vaccine development....The pandemic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has garnered the attention of scientists worldwide in the search for an effective treatment while also focusing on vaccine development.Several drugs have been used for the management of coronavirus disease 2019(COVID-19),which has affected many hospitals and health centers worldwide.Statistically significant results are lacking on the effectiveness of the experimented drugs in reducing COVID-19 morbidity or mortality,as there are very few published randomized clinical trials.Despite this,the literature offers some material for study and reflection.This opinion review attempts to address three burning questions on COVID-19 treatment options.(1)What kind of studies are currently published or ongoing in the treatment of patients with COVID-19?(2)What drugs are currently described in the literature as options of treatment for patients affected by the infection?And(3)Are there specific clinical manifestations related to COVID-19 that can be treated with a customized and targeted therapy?By answering these questions,we wish to create a summary of current COVID-19 treatments and the anti-COVID-19 treatments proposed in the recent clinical trials developed in the last 3 mo,and to describe examples of clinical manifestations of the SARS-CoV-2 infection with a cause-related treatment.展开更多
In late Dec.2019,a huge number of pneumonia cases caused by novel coronavirus were reported in China.2019-nCoV pandemic has influenced on millions of people's life across the world.This novel coronavirus was ident...In late Dec.2019,a huge number of pneumonia cases caused by novel coronavirus were reported in China.2019-nCoV pandemic has influenced on millions of people's life across the world.This novel coronavirus was identified to be similar with MERS and SARS.Therefore,researchers and academicians across the world still trying to find out vaccines,new drug molecules against SARS-CoV-2.The principle point of this review article is to explain the activity of favipiravir in preventing COVID-19.In view of constrained data available in the literature,we specify that favipiravir treatment,among all other anti-viral drugs,accompanied by oxygen inhalation therapy,maintaining fluid and electrolyte balance,and nutritional support may be helpful in fighting COVID-19.Researches were done on already approved existing anti-viral drugs for treating ebola virus,influenza virus infection and many such anti-viral agents like favipiravir,ritonavir,remdesivir,ribavirin,oseltamivir shows promising results in preventing COVID-19 infection and their clinical trials are currently undergoing in order to discover proper treatment of COVID-19.Among the aforementioned drug candidates,a broad-spectrum RNA polymerase inhibitor favipiravir,which demonstrated a promising tolerance profile and anti-viral efficacy in patients having COVID-19 manifestations.展开更多
African swine fever(ASF)is an acute,highly contagious and deadly viral disease in swine that jeopardizes the worldwide pig industry.Unfortunately,there are no authoritative vaccine and antiviral drug available for ASF...African swine fever(ASF)is an acute,highly contagious and deadly viral disease in swine that jeopardizes the worldwide pig industry.Unfortunately,there are no authoritative vaccine and antiviral drug available for ASF control.African swine fever virus(ASFV)is the etiological agent of ASF.Among the ASFV proteins,p72 is the most abundant component in the virions and thus a potential target for anti-ASFV drug design.Here,we con-structed a luciferase reporter system driven by the promoter of p72,which is transcribed by the co-transfected ASFV RNA polymerase complex.Using this system,we screened over 3200 natural product compounds and obtained three potent candidates against ASFV.We further evaluated the anti-ASFV effects and proved that among the three candidates,ailanthone(AIL)inhibits the replication of ASFV at the nanomolar concentration(IC_(50)=15 nmol/L).Our in vitro experiments indicated that the antiviral effect of AIL is associated with its inhibition of the HSP90-p23 cochaperone.Finally,we showed the antiviral activity of AIL on Zika virus and hepatitis B virus(HBV),which supports that AIL is a potential broad-spectrum antiviral agent.展开更多
The coronavirus disease 2019(COVID-19)pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection.So far,a few small-...The coronavirus disease 2019(COVID-19)pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection.So far,a few small-molecule antiviral drugs,including nirmatrelvir-ritonavir(Paxlovid),remdesivir,and molnupiravir have been marketed for the treatment of COVID-19.Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19.However,the existing treatment options have limitations,and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed.To date,four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China.These drugs include azvudine,simnotrelvir-ritonavir(Xiannuoxin),leritrelvir,and mindeudesivir(VV11).Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression.In this review,we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19.These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.展开更多
Seasonal influenza epidemics and influenza pandemics caused by influenza A virus(IAV)has resulted in millions of deaths in the world.The development of anti-IAV vaccines and therapeutics is urgently needed for prevent...Seasonal influenza epidemics and influenza pandemics caused by influenza A virus(IAV)has resulted in millions of deaths in the world.The development of anti-IAV vaccines and therapeutics is urgently needed for prevention and treatment of IAV infection and for controlling future influenza pandemics.Hemagglutinin(HA)of IAV plays a critical role in viral binding,fusion and entry,and contains the major neutralizing epitopes.Therefore,HA is an attractive target for developing anti-IAV drugs and vaccines.Here we have reviewed the recent progress in study of conformational changes of HA during viral fusion process and development of HA-based antiviral therapeutics and vaccines.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a devastating pandemic worldwide.Vaccines and antiviral drugs are the most promising candidates for combating this global epidemic,and scientists a...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a devastating pandemic worldwide.Vaccines and antiviral drugs are the most promising candidates for combating this global epidemic,and scientists all over the world have made great efforts to this end.However,manipulation of the SARS-CoV-2 should be performed in the biosafety level3 laboratory.This makes experiments complicated and time-consuming.Therefore,a safer system for working with this virus is urgently needed.Here,we report the construction of plasmid-based,non-infectious SARS-CoV-2 replicons with turbo-green fluorescent protein and/or firefly luciferase reporters by reverse genetics using transformation-associated recombination cloning in Saccharomyces cerevisiae.Replication of these replicons was achieved simply by direct transfection of cells with the replicon plasmids as evident by the expression of reporter genes.Using SARS-CoV-2 replicons,the inhibitory effects of E64-D and remdesivir on SARS-CoV-2 replication were confirmed,and the halfmaximal effective concentration(EC50)value of remdesivir and E64-D was estimated by different quantification methods respectively,indicating that these SARS-CoV-2 replicons are useful tools for antiviral drug evaluation.展开更多
Andrographolide is a labdane diterpenoid extracted and purified from the aerial parts of plants belonging to genus Andrographis(Acanthaceae).The research has shown the plant based compound is low cytotoxic,having anti...Andrographolide is a labdane diterpenoid extracted and purified from the aerial parts of plants belonging to genus Andrographis(Acanthaceae).The research has shown the plant based compound is low cytotoxic,having antimicrobial,anti-cancer,antiviral and anti-parasitic effects.Andrographolide both prevent spread as well as transmission of virus to neighboring cells by interfering with different cell signaling pathways.In addition to its medicinal value,plant has been found having nutritional value.Therefore being cost effective,easy availability and having nutritional value as a natural supplement,can be used to improve the quality of life in countries having low standard of living.Due to the limited number of effective vaccines,the plant-based antiviral drugs have provided considerable hope for fighting against the viral infections.The plant-derived compound when produced in large quantities is cost effective with low cytotoxic effects.However,much deep insight research at the molecular level is needed to develop the molecules against the viral infection.This paper aims to highlight the antiviral role of Andrographolide that can made significant contributions toward the improvement of human health and will also summarize the current status and future strategies concerning the therapeutic applications of Andrographolide to combat different viral disease in humans.展开更多
Most of the medical and nonmedical research labs,all around the world,are racing against time to produce an effective vaccine or an antiviral medicine for coronavirus disease 2019(COVID-19).Conventional medicines and ...Most of the medical and nonmedical research labs,all around the world,are racing against time to produce an effective vaccine or an antiviral medicine for coronavirus disease 2019(COVID-19).Conventional medicines and novel nano-materials including chemical and herbal-based compounds are all into positive trials toward coronaviruses and other pandemic infections.Among them,natural immune boosters have attracted physicians because of their longevity and reliability for fewer side effects.This is a review article with a detailed picture of an unexplored antiviral source with maximum potency in curing viral infections.Cyanobacteriae have been known for centuries and are rich in secondary metabolites of proteins,biopeptides,and polysaccharides for prominent antiviral action against chest infections.But detailed exploratory research is required to purify,scale-up,and commercialize the pharmacologically active agents from these drug reserves.展开更多
Background:The potential for emergence of antiviral drug resistance during influenza pandemics has raised great concern for public health.Widespread use of antiviral drugs is a significant factor in producing resistan...Background:The potential for emergence of antiviral drug resistance during influenza pandemics has raised great concern for public health.Widespread use of antiviral drugs is a significant factor in producing resistant strains.Recent studies show that some influenza viruses may gain antiviral drug resistance without a fitness penalty.This creates the possibility of strategic interaction between populations considering antiviral drug use strategies.Methods:To explain why,we develop and analyze a classical 2-player game theoretical model where each player chooses from a range of possible rates of antiviral drug use,and payoffs are derived as a function of final size of epidemic with the regular and mutant strain.Final sizes are derived from a stochastic compartmental epidemic model that captures transmission within each population and between populations,and the stochastic emergence of antiviral drug resistance.High treatment levels not only increase the spread of the resistant strain in the subject population but also affect the other population by increasing the density of the resistant strain infectious individuals due to travel between populations.Results:We found two Nash equilibria where both populations treat at a high rate,or both treat at a low rate.Hence the game theoretical analysis predicts that populations will not choose different treatment strategies than other populations,under these assumptions.The populations may choose to cooperate by maintaining a low treatment rate that does not increase the incidence of mutant strain infections or cause case importations to the other population.Alternatively,if one population is treating at a high rate,this will generate a large number of mutant infections that spread to the other population,in turn incentivizing that population to also treat at a high rate.The prediction of two separate Nash equilibria is robust to the mutation rate and the effectiveness of the drug in preventing transmission,but it is sensitive to the volume of travel between the two populations.Conclusions:Model-based evaluations of antiviral influenza drug use during a pandemic usually consider populations in isolation from one another,but our results show that strategic interactions could strongly influence a population's choice of antiviral drug use policy.Furthermore,the high treatment rate Nash equilibrium has the potential to become socially suboptimal(i.e.non-Pareto optimal)under model assumptions that might apply under other conditions.Because of the need for players to coordinate their actions,we conclude that communication and coordination between jurisdictions during influenza pandemics is a priority,especially for influenza strains that do not evolve a fitness penalty under antiviral drug resistance.展开更多
基金This research was jointly by the China Geological Survey Project Multi-Factor Urban Geological Survey of Wuhan(DD20190282)Survey and Evaluation of Riverside Urban Geological Safety in Wuhan(DD20221734).
文摘This study investigated water samples collected from the surface water and groundwater in Wuhan City,Hubei Province,China in different stages of the outbreak of the coronavirus disease 2019(hereinafter referred to as COVID-19)in the city,aiming to determine the distribution characteristics of antiviral drugs in the city’s waters.The results are as follows.The main hydrochemical type of surface water and groundwater in Wuhan was Ca-HCO3.The major chemical components in the groundwater had higher concentrations and spatial variability than those in the surface water.Two antiviral drugs and two glucocorticoids were detected in the surface water,groundwater,and sewage during the COVID-19 outbreak.Among them,chloroquine phosphate and cortisone had higher detection rates of 32.26%and 25.80%,respectively in all samples.The concentrations of residual drugs in East Lake were higher than those in other waters.The main drug detected in the waters in the later stage of the COVID-19 outbreak in Wuhan was chloroquine phosphate,whose detection rates in the surface water and the groundwater were 53.85%and 28.57%,respectively.Moreover,the detection rate and concentration of chloroquine phosphate were higher in East Lake than in Huangjia Lake.The groundwater containing chloroquine phosphate was mainly distributed along the river areas where the groundwater was highly vulnerable.The residual drugs in the surface water and the groundwater had lower concentrations in the late stage of the COVID-19 outbreak than in the middle of the outbreak,and they have not yet caused any negative impacts on the ecological environment.
基金supported by the National Natural Science Foundation of China(No.81874483,No.81273787).
文摘Background:To compare the efficacy and safety of Chinese herbal medicine combined with nucleoside antiviral drugs and nucleoside antiviral drugs alone in treating recurrent genital herpes.Methods:PubMed,Embase,Web of Science,Cochrane Library,Chinese Biomedical Literature Database,China National Knowledge Internet,VIP Database,and Wanfang Data were searched from inception to April 2021.Randomized controlled trials on the efficacy and safety of oral Chinese herbal medicine combined with nucleoside antiviral drugs for recurrent genital herpes were collected.All included trials were independently assessed by two reviewers with the Cochrane risk-of-bias tool,and a meta-analysis was conducted using Review Manager 5.4.Results:Compared with the use of nucleoside antiviral drugs alone,combination therapy with oral Chinese herbal medicine plus nucleoside antiviral drugs effectively reduced the herpes recurrence rate after the end of treatment(3 months:P=0.0002;6 months:P<0.00001;1 year:P<0.00001)and the number of recurrences each year(P<0.00001),improved the recurrent Genital Herpes Quality of Life Questionnaire score(P<0.00001),and regulated the levels of interferon-γ,interleukin-2,tumor necrosis factor-α,and T lymphocyte subsets in the peripheral blood,and the difference was statistically significant.Different subgroups reported mixed results with respect to the efficacy in the short term.The incidence of adverse reactions and the time of symptom disappearance between the two groups were not significantly different.Conclusion:Chinese herbal medicine combined with nucleoside antiviral drugs can effectively reduce the recurrence rate of recurrent genital herpes,improve the patient’s quality of life and enhance the body’s immunity.Considering the possible risk of publication bias,more high-quality randomized controlled trials are still needed to verify the conclusions of this article.
文摘We performed density functional theory (DFT) calculations for ribonucleotides and active triphosphate metabolites of candidate drugs against Coronavirus disease 2019 (Covid-19). Frontier orbitals (highest occupied molecular orbital and lowest unoccupied molecular</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">orbital) at optimized structure of each molecule were obtained. T-705RTP (active triphosphate metabolite of favipiravir) and cytidine triphosphate (CTP) have similar shapes of frontier orbitals. We also obtained similar shapes of frontier orbitals among dihydroxy GS-441524 triphosphate (GS-441524 is an active triphosphate metabolite of remdesivir) and adenosine triphosphate (ATP). From a theoretical </span><span style="font-family:Verdana;">viewpoint, we suggest T-705RTP is a CTP analogue and dihydroxy GS-441524</span><span style="font-family:Verdana;"> triphosphate is an</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">ATP analogue.
基金supported by Grants(the National Natural Science Foundation of China#32041002,#31971161,#31900546 and#81620108020)the Guangdong Science and Technology Department(#2019A1515011332)+1 种基金the Shenzhen Science and Technology Innovation Program(JSGG20200225150431472,JCYJ20190807160615255,JCYJ20190807153203560,and KQTD20180411143323605)supported by the Guangdong Zhujiang Leading Talents Programme and the National Tenthousand Talents Program。
文摘SARS-CoV-2 causes the pandemic of COVID-19 and no effective drugs for this disease are available thus far.Due to the high infectivity and pathogenicity of this virus,all studies on the live virus are strictly confined in the biosafety level 3(BSL3)laboratory but this would hinder the basic research and antiviral drug development of SARS-CoV-2 because the BSL3 facility is not commonly available and the work in the containment is costly and laborious.In this study,we constructed a reverse genetics system of SARS-CoV-2 by assembling the viral cDNA in a bacterial artificial chromosome(BAC)vector with deletion of the spike(S)gene.Transfection of the cDNA into cells results in the production of an RNA replicon that keeps the capability of genome or subgenome replication but is deficient in virion assembly and infection due to the absence of S protein.Therefore,such a replicon system is not infectious and can be used in ordinary biological laboratories.We confirmed the efficient replication of the replicon by demonstrating the expression of the subgenomic RNAs which have similar profiles to the wild-type virus.By mutational analysis of nsp12 and nsp14,we showed that the RNA polymerase,exonuclease,and cap N7 methyltransferase play essential roles in genome replication and sgRNA production.We also created a SARS-CoV-2 replicon carrying a luciferase reporter gene and this system was validated by the inhibition assays with known anti-SARS-CoV-2 inhibitors.Thus,such a one-plasmid system is biosafe and convenient to use,which will benefit both fundamental research and development of antiviral drugs.
基金partially supported by Beijing Natural Science Foundation(No.M21012)National Key Research and Development Program of China(No.2017YFC1703506,No.2018AAA0100302)National Natural Science Foundation of China(No.82174533)
文摘Due to the large-scale spread of COVID-19,which has a significant impact on human health and social economy,developing effective antiviral drugs for COVID-19 is vital to saving human lives.Various biomedical associations,e.g.,drug-virus and viral protein-host protein interactions,can be used for building biomedical knowledge graphs.Based on these sources,large-scale knowledge reasoning algorithms can be used to predict new links between antiviral drugs and viruses.To utilize the various heterogeneous biomedical associations,we proposed a fusion strategy to integrate the results of two tensor decomposition-based models(i.e.,CP-N3 and Compl Ex-N3).Sufficient experiments indicated that our method obtained high performance(MRR=0.2328).Compared with CP-N3,the mean reciprocal rank(MRR)is increased by 3.3%and compared with Compl Ex-N3,the MRR is increased by 3.5%.Meanwhile,we explored the relationship between the performance and relationship types,which indicated that there is a negative correlation(PCC=0.446,P-value=2.26 e-194)between the performance of triples predicted by our method and edge betweenness.
文摘liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.
文摘Since direct-acting antiviral agents(DAAs)have been introduced into hepatitis C virus treatment,the sustained viral response(SVR)rate has significantly increased to more than 95%.Scientific evidence supports the idea that SVR after interferon therapy has beneficial effects related to cirrhosis progression,resulting in a reduction in the incidence of hepatocellular carcinoma(HCC).However,a significant debate exists related to DAA impact on HCC development.We reviewed the current literature highlighting the controversial data related to DAA association with de novo HCC occurrence or recurrence and possible pathophysiology of HCC related to DAAs.After a review of the published literature,we believe that the current evidence does not confirm or repudiate a higher rate of de novo HCC occurrence or recurrence related to DAA therapy.More trials are needed to determine if there is an association between HCC occurrence or recurrence and DAA or if it is related to preexisting liver cirrhosis.
文摘Hepatitis B virus (HBV)-related liver disease is the leading indication for liver transplantation (LT) in Asia,especially in China.With the introduction of hepatitis B immunoglobulin (HBIG) and oral antiviral drugs,the recurrent HBV infection rate after LT has been evidently reduced.However,complete eradication of recurrent HBV infection after LT is almost impossible.Recurrent graft infection may lead to rapid disease progression and is a frequent cause of death within the fi rst year after LT.At present,the availability of new oral medications,especially nucleoside or nucleotide analogues such as adefovir dipivoxil,entecavir and tenofovir disoproxil fumarate,further strengthens our ability to treat recurrent HBV infection after LT.Moreover,since combined treatment with HBIG and antiviral agents after liver re-transplantation may play an important role in improving the prognosis of recurrent HBV infection,irreversible graft dysfunction secondary to recurrent HBV infection in spite of oral medications should no longer be considered an absolute contraindication for liver re-transplantation.Published reviews focusing on the therapeutic strategies for recurrent HBV infection after LT are very limited.In this article,the current therapeutic strategies for recurrent HBV infection after LT and evolving new trends are reviewed to guide clinical doctors to choose an optimal treatment plan in different clinical settings.
文摘Hepatitis B virus(HBV) recurrence after liver transplantation(LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication, early reports described in details recurrence and reactivation of HBV in liver transplant recipients. The evidence of a possible, severe, clinical evolution of HBV reappearance in a significant percentage of these patients, allowed to consider,for some years, HBV positivity a contraindication for LT. Moving from the old to the new millennium this picture has changed dramatically. Several studies contributed to establish efficient prophylactic protocols for HBV recurrence and with the advent of more potent anti-viral drugs an increased control of infection was achieved in transplanted patients as well as in the general immunecompetent HBV population. Success obtained in the last decade led some authors to the conclusion that HBV is now to consider just as a "mere nuisance".However, with regard to HBV and LT, outstanding issues are still on the table:(1)A standard HBV prophylaxis protocol after transplant has not yet been clearly defined;(2) The evidence of HBV resistant strains to the most potent antiviral agents is claiming for a new generation of drugs;and(3) The possibility of prophylaxis withdrawal in some patients has been demonstrated, but reliable methods for their selection are still lacking. The evolution of LT for HBV is examined in detail in this review together with the description of the strategies adopted to prevent HBV recurrence and their pros and cons.
基金supported by the National Natural Science Foundation of China(grants 82025034 and 81973392 to Huichang Bi.And grants 82274193 and 82074110 to Ling Ye)the Open Project of State Key Laboratory of Natural Medicines(grant SKLNMKF202209 to Ling Ye,China)+2 种基金the Shenzhen Science and Technology Program(No.KQTD20190929174023858 to Huichang Bi,China)Guangdong Basic and Applied Basic Research Foundation(2023A1515012859 to Shicheng Fan,China)Guangdong Medical Research Foundation(A2023109 to Shicheng Fan,China)。
文摘Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread worldwide.Effective treatments against COVID-19 remain urgently in need although vaccination significantly reduces the incidence,hospitalization,and mortality.At present,antiviral drugs including Nirmatrelvir/Ritonavir(Paxlovid^(TM)),Remdesivir,and Molnupiravir have been authorized to treat COVID-19 and become more globally available.On the other hand,traditional Chinese medicine(TCM)has been used for the treatment of epidemic diseases for a long history.Currently,various TCM formulae against COVID-19 such as Qingfei Paidu decoction,Xuanfei Baidu granule,Huashi Baidu granule,Jinhua Qinggan granule,Lianhua Qingwen capsule,and Xuebijing injection have been widely used in clinical practice in China,which may cause potential herb-drug interactions(HDIs)in patients under treatment with antiviral drugs and affect the efficacy and safety of medicines.However,information on potential HDIs between the above anti-COVID-19 drugs and TCM formulae is lacking,and thus this work seeks to summarize and highlight potential HDIs between antiviral drugs and TCM formulae against COVID-19,and especially pharmacokinetic HDIs mediated by metabolizing enzymes and/or transporters.These well-characterized HDIs could provide useful information on clinical concomitant medicine use to maximize clinical outcomes and minimize adverse and toxic effects.
文摘BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine learning algorithm(random forest).Coinfection with HBV(including patients with on-treatment reactivation of HBV infection)or HIV,extrahepatic manifestations,and renal failure did not significantly affect the treatment efficacy.CONCLUSION In patients with advanced liver disease,individualized therapy(testing for resistance-associated variants and response-guided treatment)should be considered to maximize the chance of achieving SVR.
文摘The pandemic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has garnered the attention of scientists worldwide in the search for an effective treatment while also focusing on vaccine development.Several drugs have been used for the management of coronavirus disease 2019(COVID-19),which has affected many hospitals and health centers worldwide.Statistically significant results are lacking on the effectiveness of the experimented drugs in reducing COVID-19 morbidity or mortality,as there are very few published randomized clinical trials.Despite this,the literature offers some material for study and reflection.This opinion review attempts to address three burning questions on COVID-19 treatment options.(1)What kind of studies are currently published or ongoing in the treatment of patients with COVID-19?(2)What drugs are currently described in the literature as options of treatment for patients affected by the infection?And(3)Are there specific clinical manifestations related to COVID-19 that can be treated with a customized and targeted therapy?By answering these questions,we wish to create a summary of current COVID-19 treatments and the anti-COVID-19 treatments proposed in the recent clinical trials developed in the last 3 mo,and to describe examples of clinical manifestations of the SARS-CoV-2 infection with a cause-related treatment.
文摘In late Dec.2019,a huge number of pneumonia cases caused by novel coronavirus were reported in China.2019-nCoV pandemic has influenced on millions of people's life across the world.This novel coronavirus was identified to be similar with MERS and SARS.Therefore,researchers and academicians across the world still trying to find out vaccines,new drug molecules against SARS-CoV-2.The principle point of this review article is to explain the activity of favipiravir in preventing COVID-19.In view of constrained data available in the literature,we specify that favipiravir treatment,among all other anti-viral drugs,accompanied by oxygen inhalation therapy,maintaining fluid and electrolyte balance,and nutritional support may be helpful in fighting COVID-19.Researches were done on already approved existing anti-viral drugs for treating ebola virus,influenza virus infection and many such anti-viral agents like favipiravir,ritonavir,remdesivir,ribavirin,oseltamivir shows promising results in preventing COVID-19 infection and their clinical trials are currently undergoing in order to discover proper treatment of COVID-19.Among the aforementioned drug candidates,a broad-spectrum RNA polymerase inhibitor favipiravir,which demonstrated a promising tolerance profile and anti-viral efficacy in patients having COVID-19 manifestations.
基金the State Key R&D Project to Xu Tan(2022YFE0102200)the Department of Science and Technology of Hunan Province to Xiaofeng Zheng(2019RS1050 and 2021JJ30354)。
文摘African swine fever(ASF)is an acute,highly contagious and deadly viral disease in swine that jeopardizes the worldwide pig industry.Unfortunately,there are no authoritative vaccine and antiviral drug available for ASF control.African swine fever virus(ASFV)is the etiological agent of ASF.Among the ASFV proteins,p72 is the most abundant component in the virions and thus a potential target for anti-ASFV drug design.Here,we con-structed a luciferase reporter system driven by the promoter of p72,which is transcribed by the co-transfected ASFV RNA polymerase complex.Using this system,we screened over 3200 natural product compounds and obtained three potent candidates against ASFV.We further evaluated the anti-ASFV effects and proved that among the three candidates,ailanthone(AIL)inhibits the replication of ASFV at the nanomolar concentration(IC_(50)=15 nmol/L).Our in vitro experiments indicated that the antiviral effect of AIL is associated with its inhibition of the HSP90-p23 cochaperone.Finally,we showed the antiviral activity of AIL on Zika virus and hepatitis B virus(HBV),which supports that AIL is a potential broad-spectrum antiviral agent.
基金supported by the National Major Scientific and Technological Special Project for"Significant New Drugs Development"(No.2017ZX09304007)the National Natural Science Foundation of China(Nos.82088102 and 81970728)+2 种基金the Science and Technology Commission of Shanghai Municipality(Nos.22Y31900300 and 23XD1432600)the Innovative Research Team of High-Level Local Universities in Shanghaisupported by the"National Top Young Talents"program.
文摘The coronavirus disease 2019(COVID-19)pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection.So far,a few small-molecule antiviral drugs,including nirmatrelvir-ritonavir(Paxlovid),remdesivir,and molnupiravir have been marketed for the treatment of COVID-19.Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19.However,the existing treatment options have limitations,and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed.To date,four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China.These drugs include azvudine,simnotrelvir-ritonavir(Xiannuoxin),leritrelvir,and mindeudesivir(VV11).Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression.In this review,we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19.These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
基金We thank Chungen Pan for assistance in preparing the Fig.4B.SJ and LD were supported by the US NIH grants(Nos.AI68002,AI46221)SL and RL were supported by the Natural Science Foundation of China(Grant No.30772602)the Ministry of Education’s New Century Talent Program(NCET-06-0753).
文摘Seasonal influenza epidemics and influenza pandemics caused by influenza A virus(IAV)has resulted in millions of deaths in the world.The development of anti-IAV vaccines and therapeutics is urgently needed for prevention and treatment of IAV infection and for controlling future influenza pandemics.Hemagglutinin(HA)of IAV plays a critical role in viral binding,fusion and entry,and contains the major neutralizing epitopes.Therefore,HA is an attractive target for developing anti-IAV drugs and vaccines.Here we have reviewed the recent progress in study of conformational changes of HA during viral fusion process and development of HA-based antiviral therapeutics and vaccines.
基金supported by the CAMS Innovation Fund for Medical Science(CIFMS 2016-I2M-1-014)the National Key Plan for Scientific Research and Development of China(2016YFD0500300)+1 种基金National Key R&D Program of China(2020YFA0707600)Beijing Municipal Science and Technology Project(Z201100001020005)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a devastating pandemic worldwide.Vaccines and antiviral drugs are the most promising candidates for combating this global epidemic,and scientists all over the world have made great efforts to this end.However,manipulation of the SARS-CoV-2 should be performed in the biosafety level3 laboratory.This makes experiments complicated and time-consuming.Therefore,a safer system for working with this virus is urgently needed.Here,we report the construction of plasmid-based,non-infectious SARS-CoV-2 replicons with turbo-green fluorescent protein and/or firefly luciferase reporters by reverse genetics using transformation-associated recombination cloning in Saccharomyces cerevisiae.Replication of these replicons was achieved simply by direct transfection of cells with the replicon plasmids as evident by the expression of reporter genes.Using SARS-CoV-2 replicons,the inhibitory effects of E64-D and remdesivir on SARS-CoV-2 replication were confirmed,and the halfmaximal effective concentration(EC50)value of remdesivir and E64-D was estimated by different quantification methods respectively,indicating that these SARS-CoV-2 replicons are useful tools for antiviral drug evaluation.
文摘Andrographolide is a labdane diterpenoid extracted and purified from the aerial parts of plants belonging to genus Andrographis(Acanthaceae).The research has shown the plant based compound is low cytotoxic,having antimicrobial,anti-cancer,antiviral and anti-parasitic effects.Andrographolide both prevent spread as well as transmission of virus to neighboring cells by interfering with different cell signaling pathways.In addition to its medicinal value,plant has been found having nutritional value.Therefore being cost effective,easy availability and having nutritional value as a natural supplement,can be used to improve the quality of life in countries having low standard of living.Due to the limited number of effective vaccines,the plant-based antiviral drugs have provided considerable hope for fighting against the viral infections.The plant-derived compound when produced in large quantities is cost effective with low cytotoxic effects.However,much deep insight research at the molecular level is needed to develop the molecules against the viral infection.This paper aims to highlight the antiviral role of Andrographolide that can made significant contributions toward the improvement of human health and will also summarize the current status and future strategies concerning the therapeutic applications of Andrographolide to combat different viral disease in humans.
文摘Most of the medical and nonmedical research labs,all around the world,are racing against time to produce an effective vaccine or an antiviral medicine for coronavirus disease 2019(COVID-19).Conventional medicines and novel nano-materials including chemical and herbal-based compounds are all into positive trials toward coronaviruses and other pandemic infections.Among them,natural immune boosters have attracted physicians because of their longevity and reliability for fewer side effects.This is a review article with a detailed picture of an unexplored antiviral source with maximum potency in curing viral infections.Cyanobacteriae have been known for centuries and are rich in secondary metabolites of proteins,biopeptides,and polysaccharides for prominent antiviral action against chest infections.But detailed exploratory research is required to purify,scale-up,and commercialize the pharmacologically active agents from these drug reserves.
基金This work was supported by a research grant to CTB from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada.The funders had no role in the design,analysis,writing,or decision to submit the manuscript for publication.
文摘Background:The potential for emergence of antiviral drug resistance during influenza pandemics has raised great concern for public health.Widespread use of antiviral drugs is a significant factor in producing resistant strains.Recent studies show that some influenza viruses may gain antiviral drug resistance without a fitness penalty.This creates the possibility of strategic interaction between populations considering antiviral drug use strategies.Methods:To explain why,we develop and analyze a classical 2-player game theoretical model where each player chooses from a range of possible rates of antiviral drug use,and payoffs are derived as a function of final size of epidemic with the regular and mutant strain.Final sizes are derived from a stochastic compartmental epidemic model that captures transmission within each population and between populations,and the stochastic emergence of antiviral drug resistance.High treatment levels not only increase the spread of the resistant strain in the subject population but also affect the other population by increasing the density of the resistant strain infectious individuals due to travel between populations.Results:We found two Nash equilibria where both populations treat at a high rate,or both treat at a low rate.Hence the game theoretical analysis predicts that populations will not choose different treatment strategies than other populations,under these assumptions.The populations may choose to cooperate by maintaining a low treatment rate that does not increase the incidence of mutant strain infections or cause case importations to the other population.Alternatively,if one population is treating at a high rate,this will generate a large number of mutant infections that spread to the other population,in turn incentivizing that population to also treat at a high rate.The prediction of two separate Nash equilibria is robust to the mutation rate and the effectiveness of the drug in preventing transmission,but it is sensitive to the volume of travel between the two populations.Conclusions:Model-based evaluations of antiviral influenza drug use during a pandemic usually consider populations in isolation from one another,but our results show that strategic interactions could strongly influence a population's choice of antiviral drug use policy.Furthermore,the high treatment rate Nash equilibrium has the potential to become socially suboptimal(i.e.non-Pareto optimal)under model assumptions that might apply under other conditions.Because of the need for players to coordinate their actions,we conclude that communication and coordination between jurisdictions during influenza pandemics is a priority,especially for influenza strains that do not evolve a fitness penalty under antiviral drug resistance.
