Objective:To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1(HSV-1)from the rhizome of Anemarrhena asphodeloides.Methods:Bioassay-guided isolation was conducted to separate the ac...Objective:To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1(HSV-1)from the rhizome of Anemarrhena asphodeloides.Methods:Bioassay-guided isolation was conducted to separate the active compound and its chemical structure was elucidated by spectral analysis.In vitro antiviral efficacy of active compound was detected by Cell Counting Kit-8 assay,plaque reduction assay,and fluorescence observation.RT-PCR was used to determine the viral load and the cytokine-related gene expression after HSV-1 infection.In vivo study was also conducted to further determine antiviral efficacy of an active compound against HSV-1.Results:An active compound was isolated and elucidated as mangiferin.Mangiferin significantly inhibited the replication of HSV-1 in Vero cells with a half maximal inhibitory concentration(IC_(50))of 64.0 mg/L.Time-of-addition and time-of-removal assays demonstrated that mangiferin could effectively inhibit the replication of HSV-1 in the early stage(8 h).UL12,UL42,and UL54 gene expression levels of HSV-1 in the 64 mg/L mangiferin-treated group were markedly reduced as compared with the HSV-1 group(P<0.01).Fluorescence observation showed that mangiferin attenuated the mitochondrial damage maintainingΔΨm induced by HSV-1 in Vero cells.The expression of inflammatory factors TNF-α,IL-1β,and IL-6 was remarkably increased in the virus-infected group as compared with that in the normal group(P<0.05),the levels of these inflammatory factors dropped after treatment with mangiferin.Mangiferin significantly decreased the viral load and attenuated the HSV-1-induced up-regulation of TNF-α,IL-1β,and IL-6.The relative protection rate of HSV-1-infected mice could reach up to55.5%when the concentration of mangiferin was 4 g/kg.Conclusions:Mangiferin exhibits promising antiviral activity against HSV-1 in vitro and in vivo and could be a potential antiviral agent for HSV-1.展开更多
[Objective]The research aimed to test and identify the physicochemical characters and antiviral activity in vitro of semi-finished product of the recombinant porcine rPoIFN-α. [Method]HEp-2/VSV system was used to tes...[Objective]The research aimed to test and identify the physicochemical characters and antiviral activity in vitro of semi-finished product of the recombinant porcine rPoIFN-α. [Method]HEp-2/VSV system was used to test the antiviral activity of three batches of rPoIFN-α. Using recombinant human IFN-α as reference,the titer of interferon was measured. The semi-finished product of rPoIFN-α with the known titer were treated with 0.25% trypsin,HCl and mouse anti-porcine IFN-α monoclonal antibody. And the anti-viral activity of each batch of rPoIFN-α was detected. The physicochemical characters of rPoIFN-α were evaluated. The inhibition of induced cytopathic effect of rPoIFN-α on PPV （Porcine parvovirus） and PRV （Porcine pseudorabies） on swine kidney cell （PK-15） was determined. And the antiviral activity of rPoIFN-α in vitro was observed. [Result]The titers of semi-finished products of rPoIFN-α titrated by HEp-2/VSV system could reach 1.5×105 IU/ml,with the specific activity of 1.1×106 IU/mg. The residual rate of the tier of rPoIFN-α treated by 0.25% trypsin at 37 ℃ for 1 h was less than 1%. And that treated with HCl （pH of 2.0） for 72 h was up to 95%. And that treated at 56 ℃ for 30 min and that treated by mouse anti-porcine IFN-α monoclonal antibody at 37 ℃ for 1 h were higher than 47% and about 1% respectively. The antiviral test in vitro showed that 50 and 500 IU/ml rPoIFN-α could inhibit the induced cytopathic effect of PRV and PPV on PK-15 cell lines. [Conclusion]rPoIFN-α had the basic physicochemical characters of IFN-α. And it could inhibit the induced cytopathic effect of PRV and PPV on PK-15 cell lines,but there was dosage difference.展开更多
In order to evaluate the anti-influenza virus activity of the effective monomer from Folium Isatidis (FI) in vivo,we established mice model with viral pneumonia and divided them into 3 different dose groups,then obser...In order to evaluate the anti-influenza virus activity of the effective monomer from Folium Isatidis (FI) in vivo,we established mice model with viral pneumonia and divided them into 3 different dose groups,then observed their lung indexes,pulmonary pathological changes,pulmonary virus hemagglitination titers,living time and death rates.The results showed that the monomer could reduce the pulmonary index from 2.64 to 1.93,1.63 and 1.40 (P<0.01) and decrease the hemagglitination titer from 1.15 to 0.84,0.70 and 0.59 (P<0.01).In addition,different groups of FI could significantly lessen the mortality rate from 100% to 30%,25% and 15%,and prolong the living time from 5.1d to 6.5d,8.4d and 8.9d respectively(P<0.01).The high dose (75 mg/kg/d) has the similar effect with 100 mg/kg/d dose of virazole(P>0.05),and more effective than 200 mg/kg/d dose of antiviral liquor (P<0.05).展开更多
In this study,we have investigated the antiviral activity of GuiQi polysaccharides (GQP) upon enterovirus 71 (EV71) in vitro.An assay using methyl thiazolyl tetrazolium (MTT),and analyses of cytopathic effects (CPE)we...In this study,we have investigated the antiviral activity of GuiQi polysaccharides (GQP) upon enterovirus 71 (EV71) in vitro.An assay using methyl thiazolyl tetrazolium (MTT),and analyses of cytopathic effects (CPE)were used to examine the antiviral activity of GQP upon Vero cells infected with EV71.The results revealed that GQP at concentrations below 31.2μg/mL exhibited significant antiviral effects upon EV71 when applied under three different experimental protocols.GQP was most strongly active in preventing the adsorption of EV71 to target cells and in this respect it was significantly more effective than ribavirin.In addition,it was clear that GQP could inhibit viral replication when added to cells 2 h after infection,but if added at the point of infection its effect was weak.GQP is considered to be less toxic than ribavirin,and may warrant further evaluation as a possible agent in the treatment of hand,foot and mouth disease (HFMD).展开更多
Objective: To study the antiviral properties of the five Asian medicinal plants against in vitro infection by the highly pathogenic avian influenza virus(H5N1).Methods: Crude extracts of Andrographis paniculata, Curcu...Objective: To study the antiviral properties of the five Asian medicinal plants against in vitro infection by the highly pathogenic avian influenza virus(H5N1).Methods: Crude extracts of Andrographis paniculata, Curcuma longa(C. longa),Gynostemma pentaphyllum, Kaempferia parviflora(K. parviflora), and Psidium guajava obtained by both water and ethanol extractions were investigated for their cytotoxicity in the Madin–Darby canine kidney cells. Thereafter, they were investigated in vitro for antiviral activity and cytokine response upon H5N1 virus infection.Results: The results revealed that both water and ethanol extracts of all the five studied plants showed significant antiviral activity against H5N1 virus. Among these plants,C. longa and K. parviflora showed strong anti-H5N1 activity. Thus, they were selected for further studies on their cytokine response upon virus infection. It was found that ethanol and water crude extracts of C. longa and K. parviflora induced significant upregulation of TNF-a and IFN-b m RNA expressions, suggesting their roles in the inhibition of H5N1 virus replication.Conclusions: To the best of the authors' knowledge, this study is among the earliest reports to illustrate the antiviral property of these Asian medicinal plants against the highly pathogenic avian H5N1 influenza virus. The results of this study shed light on alternative therapeutic sources for treatment of H5N1 influenza virus infection in the future.展开更多
In this study,a standard strain of HSV-1 (strain SM44) was used to investigate the antiviral activity of the recombinant Cyanovirin-N (CV-N) against Herpes simplex virus type 1 (HSV-1) in vitro and in vivo.Cytopathic ...In this study,a standard strain of HSV-1 (strain SM44) was used to investigate the antiviral activity of the recombinant Cyanovirin-N (CV-N) against Herpes simplex virus type 1 (HSV-1) in vitro and in vivo.Cytopathic effect (CPE) and MTT assays were used to evaluate the effect of CV-N on HSV-1 in Vero cells.The number of copies of HSV-DNA was detected by real-time fluorescence quantitative PCR (FQ-PCR).The results showed that CV-N had a low cytotoxicity on Vero cells with a CC50 of 359.03±0.56 μg/mL,and that it could not directly inactivate HSV-1 infectivity.CV-N not only reduced the CPE of HSV-1 when added before or after viral infection,with a 50% inhibitory concentration (IC50) with 2.26 and 30.16μg/mL respectively,but it also decreased the copies of HSV-1 DNA in infected host cells.The encephalitis model for HSV-1 infection was conducted in Kunming mice,and treated with three dosages of CV-N (0.5,5 & 10 mg/kg) which was administered intraperitoneally at 2h,3d,5d,7d post infection.The duration for the appearance of symptoms of encephalitis and the survival days were recorded and brain tissue samples were obtained for pathological examination (HE staining).Compared with the untreated control group,in the 5mg/kg CV-N and 10mg/kg CV-N treated groups,the mice suffered light symptoms and the number of survival days were more than 9d and 14d respectively.HE staining also showed that in 5mg/kg CV-N and 10mg/kg CV-N treated groups,the brain cells did not show visible changes,except for a slight inflammation.Our results demonstrated that CV-N has pronounced antiviral activity against HSV-1 both in vitro and in vivo,and it would be a promising new candidate for anti-HSV therapeutics.展开更多
Objective New rationally designed i,i＋7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America...Objective New rationally designed i,i＋7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China. Methods The antiviral activity of three i,i＋7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRFOI_AE isolates was evaluated in peripheral blood mononuclear cells （PI3MCs）. The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells. Results We found that all the stapled peptides were effective in inhibiting infection by all the primary HIV-1 isolates tested, with 50% inhibitory concentration toward viral replication （ICso） in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle virus infectivity assay. As observed with the primary isolates, the ICs0s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67. Conclusion Hydrocarbon-stapled peptides appear to have broad antiviral activity against the predominant HIV-1 viruses in China. This finding may provide the impetus to the rational design of peptides for future antiviral therapy.展开更多
Objective:To study the antiviral activity of Guanhuang Ganmao Keli on human respiratory syncytial virus(RSV)in vitro. Methods:The Guanhuang Ganmao Keli was dissolved in pure water and filtered by a 0.22 micron filter ...Objective:To study the antiviral activity of Guanhuang Ganmao Keli on human respiratory syncytial virus(RSV)in vitro. Methods:The Guanhuang Ganmao Keli was dissolved in pure water and filtered by a 0.22 micron filter to get solution. Cyclopiazonic acid(CPA)was used as positive control. The toxicity of Guanhuang Ganmao Keli on Hep-2 cells was tested by cell counting kit 8(CCK-8). The protective effect of Guanhuang Ganmao Keli on RSV was evaluated under the highest toxic concentration. Results:The TC50 and EC50 of Guanhuang Ganmao Keli is 0.647 mg/mL and 0.014 mg/mL,respectively. Guanhuang Ganmao Keli showed significant antiviral effect when added 0、2、4、6 and 8 h post-infection. Conclusion:Guanhuang Ganmao Keli is an effective antiviral agent on RSV in vitro.展开更多
Cells, pretreated with the recombinant human macrophage colony-stimulating factor (rhM-CSF) expressed in silkworm larvae, were inoculated with several viruses to observe the effect of rhM-CSF on viral replication. The...Cells, pretreated with the recombinant human macrophage colony-stimulating factor (rhM-CSF) expressed in silkworm larvae, were inoculated with several viruses to observe the effect of rhM-CSF on viral replication. The results showed that in cultures of fibroblast derived from human fetal skin-muslce tissues infected with the viruses (including VSV, rhinovirus, influenza virus type A3, HSV-1, HSV-2, adenovirus type 6 and type 11), rhM-CSF inhibited the virus-induced cytopathy, which defered or relieved the cytophathy and that in the cells derived from breast feeding rabbit kidney infected with HSV-1, rhM-CSF reduced titer of the virus in a rhM-CSF dose-dependent pattern,in which rhM-CSF with the dose of 1×106 U/L made the viral titer drop dwon over 200 times. This antiviral activity of rhM-CSF could be partially neutralized by anti-IFN-βMcAb, but not by antiTNF-α, anti-IFN-α, or anti-IFA-γ McAb, indicating the mechanism of the antiviral activity of MCSF is related to the induction of IFN-β.展开更多
Type I interferon(IFN-I)exhibits broad-spectrum antiviral properties and is commonly employed in clinical for the treatment of viral infections.In this study,we unveil SENP6 as a potent regulator of IFN-I antiviral ac...Type I interferon(IFN-I)exhibits broad-spectrum antiviral properties and is commonly employed in clinical for the treatment of viral infections.In this study,we unveil SENP6 as a potent regulator of IFN-I antiviral activity.SENP6 does not impact the production of IFN-I induced by viruses but rather modulates IFN-I-activated signaling.Mechanistically,SENP6 constitutively interacts with USP8 and inhibits the SUMOylation of USP8,consequently restricting the interaction between USP8 and IFNAR2.The dissociation of USP8 from IFNAR2 enhances IFNAR2 ubiquitination and degradation,thus attenuating IFN-I antiviral activity.Correspondingly,the downregulation of SENP6 promotes the interaction between USP8 and IFNAR2,leading to a reduction in IFNAR2 ubiquitination and,consequently,an enhancement in IFN-I-induced signaling.This study deciphers a critical deSUMOylation-deubiquitination crosstalk that finely regulates the IFN-I response to viral infection.展开更多
Severe fever with thrombocytopenia syndrome virus(SFTSV)is a tick-borne virus that causes the severe fever thrombocytopenia syndrome,which manifests as fever and haemorrhage,accompanied by severe neurological complica...Severe fever with thrombocytopenia syndrome virus(SFTSV)is a tick-borne virus that causes the severe fever thrombocytopenia syndrome,which manifests as fever and haemorrhage,accompanied by severe neurological complications.To date,no specific antiviral drugs have been approved for this indication.Herein,we investigated whether vitamin D derivatives inhibit SFTSV both in vitro and in vivo.An in vitro study demonstrated that vitamin D derivatives significantly suppressed viral RNA replication,plaque formation,and protein expression in a dosedependent manner.Subsequently,in vivo studies revealed that doxercalciferol and alfacalcidol were associated with increased survival and reduced viral RNA load in the blood.Time-of-addition assay suggested that vitamin D derivatives primarily acted during the post-entry phase of SFTSV infection.However,cytopathic effect protective activity was not observed in RIG-I immunodeficient cell line Huh7.5,and the administration of vitamin D derivatives did not improve the survival rates or reduce the blood viral loads in adult A129 mice.Further transcriptome exploration into the antiviral mechanism revealed that alfacalcidol stimulates host innate immunity to exert antiviral effects.To expand the application of vitamin D derivatives,in vitro and in vivo drug combination assays were performed,which highlighted the synergistic effects of vitamin D derivatives and T-705 on SFTSV.The combination of alfacalcidol and T-705 significantly enhanced the therapeutic effects in mice.This study highlights the potential of vitamin D derivatives against SFTSV and suggests that they may have synergistic effects with other compounds used in the treatment of SFTSV infection.展开更多
Plant virus causes massive crop losses globally.However,there is currently no effective measure to control plant viral disease.Previously,we identify an antiviral protein Rhp-PSP,produced by the bacterial Rhodopseudom...Plant virus causes massive crop losses globally.However,there is currently no effective measure to control plant viral disease.Previously,we identify an antiviral protein Rhp-PSP,produced by the bacterial Rhodopseudomonas palustris strain JSC-3b.In this study,we discover that the antiviral activity of Rhp-PSP relies on its endoribonuclease activity.Converting the arginine(R)residue at position 129 onto alanine(A)abolishs its endoribonuclease activity on coat protein(CP)RNA of tobacco mosaic virus(TMV),consequentially,compromises the antiviral activity of Rhp-PSP.Further investigation demonstrates that,the mutant Rhp-PSP^(R129A)is unable to form the homotrimer as the wild type,indicating the importance of quaternary junction for the endoribonuclease activity.Overexpression of Rhp-PSP in Nicotiana benthamiana significantly enhances the resistance against TMV of seedlings,while expression of Rhp-PSP^(R129A)did not,confirming that endoribonuclease activity is responsible for the antiviral activity of Rhp-PSP.In addition,foliar spray of Rhp-PSP solution on tomato and pepper plants significantly reduces the disease index of viral diseases,indicating that Rhp-PSP shows potential to develop antiviral agent in practice.展开更多
Type Ⅳ interferon(IFN-υ)is a recently discovered cytokine crucial for host defense against viral infections.However,the role and mechanisms of IFN-υin bacterial infections remain unexplored.This study investigated ...Type Ⅳ interferon(IFN-υ)is a recently discovered cytokine crucial for host defense against viral infections.However,the role and mechanisms of IFN-υin bacterial infections remain unexplored.This study investigated the antibacterial and antiviral functions and mechanisms of grass carp(Ctenopharyngodon idella)IFN-υ(CiIFN-υ)both in vivo and in vitro.The CiIFN-υgene was first identified and characterized in grass carp.Subsequently,the immune expression of CiIFN-υsignificantly increased following bacterial challenge,indicating its response to bacterial infections.The eukaryotic recombinant expression plasmid of CiIFN-υwas then constructed and transfected into fathead minnow(FHM)cells.Supernatants were collected and incubated with four bacterial strains,followed by plate spreading and colony counting.Results indicated that CiIFN-υexhibited more potent antibacterial activity against gram-negative bacteria compared to gram-positive bacteria and aggregated gram-negative bacteria but not gram-positive bacteria.In vivo experiments further confirmed the antibacterial function,showing high survival rates,low tissue edema and damage,reduced tissue bacterial load,and elevated proinflammatory response at the early stages of bacterial infection.In addition,the antiviral function of CiIFN-υwas confirmed through in vitro and in vivo experiments,including crystal violet staining,survival rates,tissue viral burden,and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR).This study highlights the antibacterial function and preliminary mechanism of IFN-υ,demonstrating that IFN-υpossesses dual functions against bacterial and viral infections.展开更多
Six new indole alkaloid sulfonic acids(1–6), together with two analogues(7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their struct...Six new indole alkaloid sulfonic acids(1–6), together with two analogues(7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their structures including the absolute configurations were determined by spectroscopic data analysis, combined with enzyme hydrolysis and comparison of experimental circular dichroism and calculated electronic circular dichroism spectra. In the preliminary assay, compounds 2 and 4 showed antiviral activity against Coxsackie virus B3 and influenza virus A/Hanfang/359/95(H3N2), respectively.展开更多
Severe acute respiratory syndrome(SARS) is the first severe viral epidemic we encountered his century,which once spread in more than thirty countriesin2003.1 The etiological agent of SARS has beenc onfirmed to be a n...Severe acute respiratory syndrome(SARS) is the first severe viral epidemic we encountered his century,which once spread in more than thirty countriesin2003.1 The etiological agent of SARS has beenc onfirmed to be a novel coronavirus,namely SARS coronavirus(SARS-CoV),2,3 and the first outbreak of SARS has been successfully controlled world wide,but the identification of SARS-CoV isolated from wildanimals,the emergence of some sporadic SARS cases laterafter that outbreak,all suggest that the recurrence of such an epidemic is not unlikely in the future.In this case,development of SARS vaccines and specific drugs is undoubtedlyessential to the control and prevention from the possible outbreak.4,5展开更多
Although several antiviral drugs and vaccines are available for use against hepatitis B virus （HBV）, hepatitis caused by HBV remains a major public health problem worldwide, which has not yet been resolved, and new ...Although several antiviral drugs and vaccines are available for use against hepatitis B virus （HBV）, hepatitis caused by HBV remains a major public health problem worldwide, which has not yet been resolved, and new anti-HBV drugs are in great demand. The present study was performed to investigate the anti-HBV activity of epigallocatechin- 3-gallate （EGCG）, a natural-origin compound, in HepG2 2.2.15 cells. The antiviral activity of EGCG was examined by detecting the levels of HBsAg and HBeAg in the supematant and extracellular HBV DNA. EGCG effectively suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells in a dose- and time-dependent manner, and it showed stronger effects at the level of 0.11-0.44 pmol/ml （50-200 μg/ml） than lamivudine （3TC） at 0.87 μmol/ml （200 pg/ml）. EGCG also suppressed the amount of extracellular HBV DNA. The data indicated that EGCG possessed anti-HBV activity and suggested the potential of EGCG as an effective anti-HBV agent with low toxicity.展开更多
A series of novel indole-2-carboxylate derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities.The biological results showed that some of the synthesized compounds exhi...A series of novel indole-2-carboxylate derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities.The biological results showed that some of the synthesized compounds exhibited potent broad-spectrum antiviral activity.Notably,compound 8f showed the highest SI value(17.1)to Cox B3 virus.Compound 14f showed both potent inhibitory activity against influenza A(IC_(50)=7.53μmol/L)and the highest SI value(12.1).SAR results showed that the alkyloxy at the 4-position of indole ring was not crucial to the antiviral activities.Incorporation of an acetyl substituent at the amino group disfavored antiviral activity towards RNA viruses.展开更多
Dear Editor, The 2015-2016 outbreak of Zika virus （ZIKV） fever, first reported in Brazil during early 2015 （Zanluca et al., 2015）, has infected millions of people and is a global public health concern. ZIKV infect...Dear Editor, The 2015-2016 outbreak of Zika virus （ZIKV） fever, first reported in Brazil during early 2015 （Zanluca et al., 2015）, has infected millions of people and is a global public health concern. ZIKV infections are associated with fetal microcephaly, as well as neurological complications in humans. The virus can be shed in the semen and vaginal secretions of humans, leading to sexual transmission, and unexpectedly ZIKV infections cause severe damage to the male reproductive organs in male mice （Govero et al., 2016; Ma et al., 2016）.展开更多
To find new antiviral agents,novel chalcone derivatives containing a purine moiety were designed and synthesized by combining bioactive substructures.The antiviral activities of the derivatives against tobacco mosaic ...To find new antiviral agents,novel chalcone derivatives containing a purine moiety were designed and synthesized by combining bioactive substructures.The antiviral activities of the derivatives against tobacco mosaic virus （TMV） and cucumber mosaic virus （CMV） were evaluated.Results showed that most of the derivatives showed antiviral activities.Compounds 3n and 3p exhibited excellent curative,protective and inactivation activities against TMV,with the EC50values of 452.4,416.2,241.2 and 438.7,418.6,261.7 μg·mL-1,respectively,which were better than those of ribavirin （585.8,436.0 and 268.7 μg·mL-1）.Compounds 3n and 3p showed remarkable curative and protective activities against CMV.Compound 3n showed a moderate affinity to TMV coat protein,with binding constant Ka and Kd values of 1.5 × 104 L·mol-1 and 79.8 μmol·L-1,respectively.These findings provided an important structural insight for further designs of highly active chalcone derivatives and a basis for further study on their mechanism of action.展开更多
New N-adamantyl-2-amino-acylamides（3a--3f） and N-adamantyl-2-phenoxy-acetamides（6a--6d） were designed and synthesized by the modification of the amino group of amantadine I and the structures were confirmed by mas...New N-adamantyl-2-amino-acylamides（3a--3f） and N-adamantyl-2-phenoxy-acetamides（6a--6d） were designed and synthesized by the modification of the amino group of amantadine I and the structures were confirmed by mass spectra（MS） and 1H NMR spectra. The antiviral potencies of the synthesized compounds were evaluated against the replication of influenza virus A/H3N2 subtype in Madin-Darby canine kidney（MDCK） cells. Among the amantadine derivatives, compound 3a bad the strongest antiviral potency and showed activity similar to that of amantadine. Interestingly, the bulky and extended lipophilic moieties on the a-position of the carbonyl group resulted in decreases in potency.展开更多
基金supported by Project of Zhejiang Basic Public Benefit Research of Zhejiang Province (NO.LGF22Y145002)。
文摘Objective:To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1(HSV-1)from the rhizome of Anemarrhena asphodeloides.Methods:Bioassay-guided isolation was conducted to separate the active compound and its chemical structure was elucidated by spectral analysis.In vitro antiviral efficacy of active compound was detected by Cell Counting Kit-8 assay,plaque reduction assay,and fluorescence observation.RT-PCR was used to determine the viral load and the cytokine-related gene expression after HSV-1 infection.In vivo study was also conducted to further determine antiviral efficacy of an active compound against HSV-1.Results:An active compound was isolated and elucidated as mangiferin.Mangiferin significantly inhibited the replication of HSV-1 in Vero cells with a half maximal inhibitory concentration(IC_(50))of 64.0 mg/L.Time-of-addition and time-of-removal assays demonstrated that mangiferin could effectively inhibit the replication of HSV-1 in the early stage(8 h).UL12,UL42,and UL54 gene expression levels of HSV-1 in the 64 mg/L mangiferin-treated group were markedly reduced as compared with the HSV-1 group(P<0.01).Fluorescence observation showed that mangiferin attenuated the mitochondrial damage maintainingΔΨm induced by HSV-1 in Vero cells.The expression of inflammatory factors TNF-α,IL-1β,and IL-6 was remarkably increased in the virus-infected group as compared with that in the normal group(P<0.05),the levels of these inflammatory factors dropped after treatment with mangiferin.Mangiferin significantly decreased the viral load and attenuated the HSV-1-induced up-regulation of TNF-α,IL-1β,and IL-6.The relative protection rate of HSV-1-infected mice could reach up to55.5%when the concentration of mangiferin was 4 g/kg.Conclusions:Mangiferin exhibits promising antiviral activity against HSV-1 in vitro and in vivo and could be a potential antiviral agent for HSV-1.
基金Supported by Natural Science Research Project of Anhui Educational Committee (2004kj218 )Major Special Program of Science and Technology Grand Plan of Anhui Province (08010302179)~~
文摘[Objective]The research aimed to test and identify the physicochemical characters and antiviral activity in vitro of semi-finished product of the recombinant porcine rPoIFN-α. [Method]HEp-2/VSV system was used to test the antiviral activity of three batches of rPoIFN-α. Using recombinant human IFN-α as reference,the titer of interferon was measured. The semi-finished product of rPoIFN-α with the known titer were treated with 0.25% trypsin,HCl and mouse anti-porcine IFN-α monoclonal antibody. And the anti-viral activity of each batch of rPoIFN-α was detected. The physicochemical characters of rPoIFN-α were evaluated. The inhibition of induced cytopathic effect of rPoIFN-α on PPV （Porcine parvovirus） and PRV （Porcine pseudorabies） on swine kidney cell （PK-15） was determined. And the antiviral activity of rPoIFN-α in vitro was observed. [Result]The titers of semi-finished products of rPoIFN-α titrated by HEp-2/VSV system could reach 1.5×105 IU/ml,with the specific activity of 1.1×106 IU/mg. The residual rate of the tier of rPoIFN-α treated by 0.25% trypsin at 37 ℃ for 1 h was less than 1%. And that treated with HCl （pH of 2.0） for 72 h was up to 95%. And that treated at 56 ℃ for 30 min and that treated by mouse anti-porcine IFN-α monoclonal antibody at 37 ℃ for 1 h were higher than 47% and about 1% respectively. The antiviral test in vitro showed that 50 and 500 IU/ml rPoIFN-α could inhibit the induced cytopathic effect of PRV and PPV on PK-15 cell lines. [Conclusion]rPoIFN-α had the basic physicochemical characters of IFN-α. And it could inhibit the induced cytopathic effect of PRV and PPV on PK-15 cell lines,but there was dosage difference.
基金Natural Science Foundation of South Central University for Nationalities (YZQ05011)
文摘In order to evaluate the anti-influenza virus activity of the effective monomer from Folium Isatidis (FI) in vivo,we established mice model with viral pneumonia and divided them into 3 different dose groups,then observed their lung indexes,pulmonary pathological changes,pulmonary virus hemagglitination titers,living time and death rates.The results showed that the monomer could reduce the pulmonary index from 2.64 to 1.93,1.63 and 1.40 (P<0.01) and decrease the hemagglitination titer from 1.15 to 0.84,0.70 and 0.59 (P<0.01).In addition,different groups of FI could significantly lessen the mortality rate from 100% to 30%,25% and 15%,and prolong the living time from 5.1d to 6.5d,8.4d and 8.9d respectively(P<0.01).The high dose (75 mg/kg/d) has the similar effect with 100 mg/kg/d dose of virazole(P>0.05),and more effective than 200 mg/kg/d dose of antiviral liquor (P<0.05).
基金supported by research grants from The National Natural Science Foundation of China(NO81260070)The Project of Science and Technology of Lanzhou(NO 2011-1-71)The Doctor Project of Lanzhou University of Technology(NO 0908ZXC127)
文摘In this study,we have investigated the antiviral activity of GuiQi polysaccharides (GQP) upon enterovirus 71 (EV71) in vitro.An assay using methyl thiazolyl tetrazolium (MTT),and analyses of cytopathic effects (CPE)were used to examine the antiviral activity of GQP upon Vero cells infected with EV71.The results revealed that GQP at concentrations below 31.2μg/mL exhibited significant antiviral effects upon EV71 when applied under three different experimental protocols.GQP was most strongly active in preventing the adsorption of EV71 to target cells and in this respect it was significantly more effective than ribavirin.In addition,it was clear that GQP could inhibit viral replication when added to cells 2 h after infection,but if added at the point of infection its effect was weak.GQP is considered to be less toxic than ribavirin,and may warrant further evaluation as a possible agent in the treatment of hand,foot and mouth disease (HFMD).
基金supported by the Young Researcher Award of Chiang Mai University grant number R000009357the CMU Mid-Career Research Fellowship Program,Chiang Mai University,Chiang Mai,Thailand
文摘Objective: To study the antiviral properties of the five Asian medicinal plants against in vitro infection by the highly pathogenic avian influenza virus(H5N1).Methods: Crude extracts of Andrographis paniculata, Curcuma longa(C. longa),Gynostemma pentaphyllum, Kaempferia parviflora(K. parviflora), and Psidium guajava obtained by both water and ethanol extractions were investigated for their cytotoxicity in the Madin–Darby canine kidney cells. Thereafter, they were investigated in vitro for antiviral activity and cytokine response upon H5N1 virus infection.Results: The results revealed that both water and ethanol extracts of all the five studied plants showed significant antiviral activity against H5N1 virus. Among these plants,C. longa and K. parviflora showed strong anti-H5N1 activity. Thus, they were selected for further studies on their cytokine response upon virus infection. It was found that ethanol and water crude extracts of C. longa and K. parviflora induced significant upregulation of TNF-a and IFN-b m RNA expressions, suggesting their roles in the inhibition of H5N1 virus replication.Conclusions: To the best of the authors' knowledge, this study is among the earliest reports to illustrate the antiviral property of these Asian medicinal plants against the highly pathogenic avian H5N1 influenza virus. The results of this study shed light on alternative therapeutic sources for treatment of H5N1 influenza virus infection in the future.
基金Science and Technology Development Project of Shandong province (2005GG3202068)
文摘In this study,a standard strain of HSV-1 (strain SM44) was used to investigate the antiviral activity of the recombinant Cyanovirin-N (CV-N) against Herpes simplex virus type 1 (HSV-1) in vitro and in vivo.Cytopathic effect (CPE) and MTT assays were used to evaluate the effect of CV-N on HSV-1 in Vero cells.The number of copies of HSV-DNA was detected by real-time fluorescence quantitative PCR (FQ-PCR).The results showed that CV-N had a low cytotoxicity on Vero cells with a CC50 of 359.03±0.56 μg/mL,and that it could not directly inactivate HSV-1 infectivity.CV-N not only reduced the CPE of HSV-1 when added before or after viral infection,with a 50% inhibitory concentration (IC50) with 2.26 and 30.16μg/mL respectively,but it also decreased the copies of HSV-1 DNA in infected host cells.The encephalitis model for HSV-1 infection was conducted in Kunming mice,and treated with three dosages of CV-N (0.5,5 & 10 mg/kg) which was administered intraperitoneally at 2h,3d,5d,7d post infection.The duration for the appearance of symptoms of encephalitis and the survival days were recorded and brain tissue samples were obtained for pathological examination (HE staining).Compared with the untreated control group,in the 5mg/kg CV-N and 10mg/kg CV-N treated groups,the mice suffered light symptoms and the number of survival days were more than 9d and 14d respectively.HE staining also showed that in 5mg/kg CV-N and 10mg/kg CV-N treated groups,the brain cells did not show visible changes,except for a slight inflammation.Our results demonstrated that CV-N has pronounced antiviral activity against HSV-1 both in vitro and in vivo,and it would be a promising new candidate for anti-HSV therapeutics.
基金supported by the National Natural Science Foundation of China(NSFC,No.81261120384)the Key Project of the State Key Laboratory for Infectious Diseases Prevention and Control(SKLID,No.2011SKLID102)+3 种基金the Ministry of Science and Technology of China(2012ZX10001-002)the European Research Infrastructures for Poverty Related Diseases(312661)by funds from NIH Grant RO1 AI104416(AKD)the New York Blood Center(AKD)
文摘Objective New rationally designed i,i＋7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China. Methods The antiviral activity of three i,i＋7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRFOI_AE isolates was evaluated in peripheral blood mononuclear cells （PI3MCs）. The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells. Results We found that all the stapled peptides were effective in inhibiting infection by all the primary HIV-1 isolates tested, with 50% inhibitory concentration toward viral replication （ICso） in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle virus infectivity assay. As observed with the primary isolates, the ICs0s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67. Conclusion Hydrocarbon-stapled peptides appear to have broad antiviral activity against the predominant HIV-1 viruses in China. This finding may provide the impetus to the rational design of peptides for future antiviral therapy.
基金Hainan Provincial Natural Science Foundation of China(No.818MS070)。
文摘Objective:To study the antiviral activity of Guanhuang Ganmao Keli on human respiratory syncytial virus(RSV)in vitro. Methods:The Guanhuang Ganmao Keli was dissolved in pure water and filtered by a 0.22 micron filter to get solution. Cyclopiazonic acid(CPA)was used as positive control. The toxicity of Guanhuang Ganmao Keli on Hep-2 cells was tested by cell counting kit 8(CCK-8). The protective effect of Guanhuang Ganmao Keli on RSV was evaluated under the highest toxic concentration. Results:The TC50 and EC50 of Guanhuang Ganmao Keli is 0.647 mg/mL and 0.014 mg/mL,respectively. Guanhuang Ganmao Keli showed significant antiviral effect when added 0、2、4、6 and 8 h post-infection. Conclusion:Guanhuang Ganmao Keli is an effective antiviral agent on RSV in vitro.
文摘Cells, pretreated with the recombinant human macrophage colony-stimulating factor (rhM-CSF) expressed in silkworm larvae, were inoculated with several viruses to observe the effect of rhM-CSF on viral replication. The results showed that in cultures of fibroblast derived from human fetal skin-muslce tissues infected with the viruses (including VSV, rhinovirus, influenza virus type A3, HSV-1, HSV-2, adenovirus type 6 and type 11), rhM-CSF inhibited the virus-induced cytopathy, which defered or relieved the cytophathy and that in the cells derived from breast feeding rabbit kidney infected with HSV-1, rhM-CSF reduced titer of the virus in a rhM-CSF dose-dependent pattern,in which rhM-CSF with the dose of 1×106 U/L made the viral titer drop dwon over 200 times. This antiviral activity of rhM-CSF could be partially neutralized by anti-IFN-βMcAb, but not by antiTNF-α, anti-IFN-α, or anti-IFA-γ McAb, indicating the mechanism of the antiviral activity of MCSF is related to the induction of IFN-β.
基金National Natural Science Foundation of China(31970844,32170927)to SDX.
文摘Type I interferon(IFN-I)exhibits broad-spectrum antiviral properties and is commonly employed in clinical for the treatment of viral infections.In this study,we unveil SENP6 as a potent regulator of IFN-I antiviral activity.SENP6 does not impact the production of IFN-I induced by viruses but rather modulates IFN-I-activated signaling.Mechanistically,SENP6 constitutively interacts with USP8 and inhibits the SUMOylation of USP8,consequently restricting the interaction between USP8 and IFNAR2.The dissociation of USP8 from IFNAR2 enhances IFNAR2 ubiquitination and degradation,thus attenuating IFN-I antiviral activity.Correspondingly,the downregulation of SENP6 promotes the interaction between USP8 and IFNAR2,leading to a reduction in IFNAR2 ubiquitination and,consequently,an enhancement in IFN-I-induced signaling.This study deciphers a critical deSUMOylation-deubiquitination crosstalk that finely regulates the IFN-I response to viral infection.
基金supported by the National Natural Science Foundation of China(NSFC,grants 81773631,to R.C.grants 82304383 J.Y.)+1 种基金the National Science and Technology Major Projects for“Major New Drugs Innovation and Development”,China(2018ZX09711003,to W.Z.)the Hainan Provincial Natural Science Foundation of China(822QN299,to J.Y.).
文摘Severe fever with thrombocytopenia syndrome virus(SFTSV)is a tick-borne virus that causes the severe fever thrombocytopenia syndrome,which manifests as fever and haemorrhage,accompanied by severe neurological complications.To date,no specific antiviral drugs have been approved for this indication.Herein,we investigated whether vitamin D derivatives inhibit SFTSV both in vitro and in vivo.An in vitro study demonstrated that vitamin D derivatives significantly suppressed viral RNA replication,plaque formation,and protein expression in a dosedependent manner.Subsequently,in vivo studies revealed that doxercalciferol and alfacalcidol were associated with increased survival and reduced viral RNA load in the blood.Time-of-addition assay suggested that vitamin D derivatives primarily acted during the post-entry phase of SFTSV infection.However,cytopathic effect protective activity was not observed in RIG-I immunodeficient cell line Huh7.5,and the administration of vitamin D derivatives did not improve the survival rates or reduce the blood viral loads in adult A129 mice.Further transcriptome exploration into the antiviral mechanism revealed that alfacalcidol stimulates host innate immunity to exert antiviral effects.To expand the application of vitamin D derivatives,in vitro and in vivo drug combination assays were performed,which highlighted the synergistic effects of vitamin D derivatives and T-705 on SFTSV.The combination of alfacalcidol and T-705 significantly enhanced the therapeutic effects in mice.This study highlights the potential of vitamin D derivatives against SFTSV and suggests that they may have synergistic effects with other compounds used in the treatment of SFTSV infection.
基金supported by the National Key R&D Program of China(2022YFD1400700)the Key Research and Development Program of Hunan Province,China(2022NK2014)+2 种基金the Hunan Natural Science Foundation,China(2022JJ40234)the Agricultural Science and Technology Innovation Fund Project of Hunan Province,China(2022CX1)the Changsha Natural Science Foundation,China(kq2202338).
文摘Plant virus causes massive crop losses globally.However,there is currently no effective measure to control plant viral disease.Previously,we identify an antiviral protein Rhp-PSP,produced by the bacterial Rhodopseudomonas palustris strain JSC-3b.In this study,we discover that the antiviral activity of Rhp-PSP relies on its endoribonuclease activity.Converting the arginine(R)residue at position 129 onto alanine(A)abolishs its endoribonuclease activity on coat protein(CP)RNA of tobacco mosaic virus(TMV),consequentially,compromises the antiviral activity of Rhp-PSP.Further investigation demonstrates that,the mutant Rhp-PSP^(R129A)is unable to form the homotrimer as the wild type,indicating the importance of quaternary junction for the endoribonuclease activity.Overexpression of Rhp-PSP in Nicotiana benthamiana significantly enhances the resistance against TMV of seedlings,while expression of Rhp-PSP^(R129A)did not,confirming that endoribonuclease activity is responsible for the antiviral activity of Rhp-PSP.In addition,foliar spray of Rhp-PSP solution on tomato and pepper plants significantly reduces the disease index of viral diseases,indicating that Rhp-PSP shows potential to develop antiviral agent in practice.
基金supported by the Biological Breeding-Major Projects(2023ZD04065)。
文摘Type Ⅳ interferon(IFN-υ)is a recently discovered cytokine crucial for host defense against viral infections.However,the role and mechanisms of IFN-υin bacterial infections remain unexplored.This study investigated the antibacterial and antiviral functions and mechanisms of grass carp(Ctenopharyngodon idella)IFN-υ(CiIFN-υ)both in vivo and in vitro.The CiIFN-υgene was first identified and characterized in grass carp.Subsequently,the immune expression of CiIFN-υsignificantly increased following bacterial challenge,indicating its response to bacterial infections.The eukaryotic recombinant expression plasmid of CiIFN-υwas then constructed and transfected into fathead minnow(FHM)cells.Supernatants were collected and incubated with four bacterial strains,followed by plate spreading and colony counting.Results indicated that CiIFN-υexhibited more potent antibacterial activity against gram-negative bacteria compared to gram-positive bacteria and aggregated gram-negative bacteria but not gram-positive bacteria.In vivo experiments further confirmed the antibacterial function,showing high survival rates,low tissue edema and damage,reduced tissue bacterial load,and elevated proinflammatory response at the early stages of bacterial infection.In addition,the antiviral function of CiIFN-υwas confirmed through in vitro and in vivo experiments,including crystal violet staining,survival rates,tissue viral burden,and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR).This study highlights the antibacterial function and preliminary mechanism of IFN-υ,demonstrating that IFN-υpossesses dual functions against bacterial and viral infections.
基金Financial support from the National Natural Sciences Foundation of China(NNSFCgrant Nos.81373287,81630094 and 30825044)is acknowledged
文摘Six new indole alkaloid sulfonic acids(1–6), together with two analogues(7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their structures including the absolute configurations were determined by spectroscopic data analysis, combined with enzyme hydrolysis and comparison of experimental circular dichroism and calculated electronic circular dichroism spectra. In the preliminary assay, compounds 2 and 4 showed antiviral activity against Coxsackie virus B3 and influenza virus A/Hanfang/359/95(H3N2), respectively.
文摘Severe acute respiratory syndrome(SARS) is the first severe viral epidemic we encountered his century,which once spread in more than thirty countriesin2003.1 The etiological agent of SARS has beenc onfirmed to be a novel coronavirus,namely SARS coronavirus(SARS-CoV),2,3 and the first outbreak of SARS has been successfully controlled world wide,but the identification of SARS-CoV isolated from wildanimals,the emergence of some sporadic SARS cases laterafter that outbreak,all suggest that the recurrence of such an epidemic is not unlikely in the future.In this case,development of SARS vaccines and specific drugs is undoubtedlyessential to the control and prevention from the possible outbreak.4,5
基金Project supported by the National Commonweal Industry Special Research Foundation of China(No.200807020)the National Natural Science Foundation of China(Nos.30973947 and 81173571)
文摘Although several antiviral drugs and vaccines are available for use against hepatitis B virus （HBV）, hepatitis caused by HBV remains a major public health problem worldwide, which has not yet been resolved, and new anti-HBV drugs are in great demand. The present study was performed to investigate the anti-HBV activity of epigallocatechin- 3-gallate （EGCG）, a natural-origin compound, in HepG2 2.2.15 cells. The antiviral activity of EGCG was examined by detecting the levels of HBsAg and HBeAg in the supematant and extracellular HBV DNA. EGCG effectively suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells in a dose- and time-dependent manner, and it showed stronger effects at the level of 0.11-0.44 pmol/ml （50-200 μg/ml） than lamivudine （3TC） at 0.87 μmol/ml （200 pg/ml）. EGCG also suppressed the amount of extracellular HBV DNA. The data indicated that EGCG possessed anti-HBV activity and suggested the potential of EGCG as an effective anti-HBV agent with low toxicity.
基金This work was supported by the National Natural Science Foundation of China(No.81273439)the National Mega-project for Innovative Drugs(No.2012ZX09301002-001-024-02).
文摘A series of novel indole-2-carboxylate derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities.The biological results showed that some of the synthesized compounds exhibited potent broad-spectrum antiviral activity.Notably,compound 8f showed the highest SI value(17.1)to Cox B3 virus.Compound 14f showed both potent inhibitory activity against influenza A(IC_(50)=7.53μmol/L)and the highest SI value(12.1).SAR results showed that the alkyloxy at the 4-position of indole ring was not crucial to the antiviral activities.Incorporation of an acetyl substituent at the amino group disfavored antiviral activity towards RNA viruses.
文摘Dear Editor, The 2015-2016 outbreak of Zika virus （ZIKV） fever, first reported in Brazil during early 2015 （Zanluca et al., 2015）, has infected millions of people and is a global public health concern. ZIKV infections are associated with fetal microcephaly, as well as neurological complications in humans. The virus can be shed in the semen and vaginal secretions of humans, leading to sexual transmission, and unexpectedly ZIKV infections cause severe damage to the male reproductive organs in male mice （Govero et al., 2016; Ma et al., 2016）.
文摘To find new antiviral agents,novel chalcone derivatives containing a purine moiety were designed and synthesized by combining bioactive substructures.The antiviral activities of the derivatives against tobacco mosaic virus （TMV） and cucumber mosaic virus （CMV） were evaluated.Results showed that most of the derivatives showed antiviral activities.Compounds 3n and 3p exhibited excellent curative,protective and inactivation activities against TMV,with the EC50values of 452.4,416.2,241.2 and 438.7,418.6,261.7 μg·mL-1,respectively,which were better than those of ribavirin （585.8,436.0 and 268.7 μg·mL-1）.Compounds 3n and 3p showed remarkable curative and protective activities against CMV.Compound 3n showed a moderate affinity to TMV coat protein,with binding constant Ka and Kd values of 1.5 × 104 L·mol-1 and 79.8 μmol·L-1,respectively.These findings provided an important structural insight for further designs of highly active chalcone derivatives and a basis for further study on their mechanism of action.
文摘New N-adamantyl-2-amino-acylamides（3a--3f） and N-adamantyl-2-phenoxy-acetamides（6a--6d） were designed and synthesized by the modification of the amino group of amantadine I and the structures were confirmed by mass spectra（MS） and 1H NMR spectra. The antiviral potencies of the synthesized compounds were evaluated against the replication of influenza virus A/H3N2 subtype in Madin-Darby canine kidney（MDCK） cells. Among the amantadine derivatives, compound 3a bad the strongest antiviral potency and showed activity similar to that of amantadine. Interestingly, the bulky and extended lipophilic moieties on the a-position of the carbonyl group resulted in decreases in potency.
