Lassa hemorrhagic fever,caused by Lassa mammarenavirus(LASV)infection,accumulates up to 5000 deaths every year.Currently,there is no vaccine available to combat this disease.In this study,a library of 200 bioactive co...Lassa hemorrhagic fever,caused by Lassa mammarenavirus(LASV)infection,accumulates up to 5000 deaths every year.Currently,there is no vaccine available to combat this disease.In this study,a library of 200 bioactive compounds was virtually screened to study their drug-likeness with the capacity to block theα-dystroglycan(α-DG)receptor and prevent LASV influx.Following rigorous absorption,distribution,metabolism,and excretion(ADME)and quantitative structure-activity relationship(QSAR)profiling,molecular docking was conducted with the top ligands against theα-DG receptor.The compounds chrysin,reticuline,and 3-caffeoylshikimic acid emerged as the top three ligands in terms of binding affinity.Post-docking analysis revealed that interactions with Arg76,Asn224,Ser259,and Lys302 amino acid residues of the receptor protein were important for the optimum binding affinity of ligands.Molecular dynamics simulation was performed comprehensively to study the stability of the protein-ligand complexes.In-depth assessment of root-mean-square deviation(RMSD),root mean square fluctuation(RMSF),polar surface area(PSA),B-Factor,radius of gyration(Rg),solvent accessible surface area(SASA),and molecular surface area(MolSA)values of the protein-ligand complexes affirmed that the candidates with the best binding affinity formed the most stable protein-ligand complexes.To authenticate the potentialities of the ligands as target-specific drugs,an in vivo study is underway in real time as the continuation of the research.展开更多
Immunotherapies boosting the immune system's ability to target cancer cells are promising for the treatment of various tumor types,yet clinical responses differ among patients and cancers.Recently,there has been i...Immunotherapies boosting the immune system's ability to target cancer cells are promising for the treatment of various tumor types,yet clinical responses differ among patients and cancers.Recently,there has been increasing interest in novel cancer immunotherapy practices aimed at triggering T cell-mediated anti-tumor responses.Antigen-directed cytotoxicity mediated by T lymphocytes has become a central focal point in the battle against cancer utilizing the immune system.The molecular and cellular mechanisms involved in the actions of T lymphocytes have directed new therapeutic approaches in cancer immunotherapy,including checkpoint blockade,adoptive and chimeric antigen receptor(CAR)T cell therapy,and cancer vaccinology.This review addresses all the strategies targeting tumor pathogenesis,including metabolic pathways,to evaluate the clinical significance of current and future immunotherapies for patients with cancer,which are further engaged in T cell activation,differentiation,and response against tumors.展开更多
The COVID-19 caused by SARS-CoV-2 has resulted in millions of people being infected and thousands of deaths globally since November 2019.To date,no unique therapeutic agent has been developed to slow the progression o...The COVID-19 caused by SARS-CoV-2 has resulted in millions of people being infected and thousands of deaths globally since November 2019.To date,no unique therapeutic agent has been developed to slow the progression of this pandemic.Despite possessing antiviral traits the potential of bacteriocins to combat SARS-CoV-2 infection has not been fully investigated.This review summarizes the mechanisms by which bacteriocins can be manipulated and implemented as effective virus entry blockers with infection suppression potential properties to highly transmissible viruses through comprehensive immune modulations that are potentially effective against COVID-19.These antimicrobial peptides have been suggested as effective antiviral therapeutics and therapeutic supplements to prevent rapid virus transmission.This review also provides a new insight into the cellular and molecular alterations which have made SARS-CoV-2 self-modified with diversified infection patterns.In addition,the possible applications of antimicrobial peptides through both natural and induced mechanisms in infection prevention perspectives on changeable virulence cases are comprehensively analyzed.Specific attention is given to the antiviral mechanisms of the molecules along with their integrative use with synthetic biology and nanosensor technology for rapid detection.Novel bacteriocin based therapeutics with cutting-edge technologies might be potential substitutes for existing time-consuming and expensive approaches to fight this newly emerged global threat.展开更多
文摘Lassa hemorrhagic fever,caused by Lassa mammarenavirus(LASV)infection,accumulates up to 5000 deaths every year.Currently,there is no vaccine available to combat this disease.In this study,a library of 200 bioactive compounds was virtually screened to study their drug-likeness with the capacity to block theα-dystroglycan(α-DG)receptor and prevent LASV influx.Following rigorous absorption,distribution,metabolism,and excretion(ADME)and quantitative structure-activity relationship(QSAR)profiling,molecular docking was conducted with the top ligands against theα-DG receptor.The compounds chrysin,reticuline,and 3-caffeoylshikimic acid emerged as the top three ligands in terms of binding affinity.Post-docking analysis revealed that interactions with Arg76,Asn224,Ser259,and Lys302 amino acid residues of the receptor protein were important for the optimum binding affinity of ligands.Molecular dynamics simulation was performed comprehensively to study the stability of the protein-ligand complexes.In-depth assessment of root-mean-square deviation(RMSD),root mean square fluctuation(RMSF),polar surface area(PSA),B-Factor,radius of gyration(Rg),solvent accessible surface area(SASA),and molecular surface area(MolSA)values of the protein-ligand complexes affirmed that the candidates with the best binding affinity formed the most stable protein-ligand complexes.To authenticate the potentialities of the ligands as target-specific drugs,an in vivo study is underway in real time as the continuation of the research.
文摘Immunotherapies boosting the immune system's ability to target cancer cells are promising for the treatment of various tumor types,yet clinical responses differ among patients and cancers.Recently,there has been increasing interest in novel cancer immunotherapy practices aimed at triggering T cell-mediated anti-tumor responses.Antigen-directed cytotoxicity mediated by T lymphocytes has become a central focal point in the battle against cancer utilizing the immune system.The molecular and cellular mechanisms involved in the actions of T lymphocytes have directed new therapeutic approaches in cancer immunotherapy,including checkpoint blockade,adoptive and chimeric antigen receptor(CAR)T cell therapy,and cancer vaccinology.This review addresses all the strategies targeting tumor pathogenesis,including metabolic pathways,to evaluate the clinical significance of current and future immunotherapies for patients with cancer,which are further engaged in T cell activation,differentiation,and response against tumors.
基金the authority of Research Publication Guardians(RPG,Government License No.05-060-06021)for providing logistic support and suggestions which were important to the successful completion of this review。
文摘The COVID-19 caused by SARS-CoV-2 has resulted in millions of people being infected and thousands of deaths globally since November 2019.To date,no unique therapeutic agent has been developed to slow the progression of this pandemic.Despite possessing antiviral traits the potential of bacteriocins to combat SARS-CoV-2 infection has not been fully investigated.This review summarizes the mechanisms by which bacteriocins can be manipulated and implemented as effective virus entry blockers with infection suppression potential properties to highly transmissible viruses through comprehensive immune modulations that are potentially effective against COVID-19.These antimicrobial peptides have been suggested as effective antiviral therapeutics and therapeutic supplements to prevent rapid virus transmission.This review also provides a new insight into the cellular and molecular alterations which have made SARS-CoV-2 self-modified with diversified infection patterns.In addition,the possible applications of antimicrobial peptides through both natural and induced mechanisms in infection prevention perspectives on changeable virulence cases are comprehensively analyzed.Specific attention is given to the antiviral mechanisms of the molecules along with their integrative use with synthetic biology and nanosensor technology for rapid detection.Novel bacteriocin based therapeutics with cutting-edge technologies might be potential substitutes for existing time-consuming and expensive approaches to fight this newly emerged global threat.
