Protein p7 of HCV is a 63 amino acid channel forming membrane protein essential for the progression ofviral infection and the sensitivity of this channel to small-molecule inhibitors renders p7 a potentialtarget for n...Protein p7 of HCV is a 63 amino acid channel forming membrane protein essential for the progression ofviral infection and the sensitivity of this channel to small-molecule inhibitors renders p7 a potentialtarget for novel therapies against HCV infection. Previous biochemical experiments suggested that theHis17 of p7 is a pore-lining residue and solvated-exposed to participate in channel gating. However, arecent NMR structural identification of the p7 hexamer in dodecylphosphocholine （DPC） micellesindicated that the His17 is embedded into the protein matrix. In this work, we performed moleculardynamic simulations to bridge the controversial observations. Our results illustrated that byincorporating the cholesterol into DOPC membranes to mimic an actual membrane-like composition,the orientation of His17 in the hexameric bundles spontaneously access to the central pore region,indicating a versatile property of the p7 viroporin conformation that could be voluntarily influenced byits surrounding environments.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)recently emerged as a highly virulent respiratory pathogen that is known as the causative agent of coronavirus disease 2019(COVID-19).Diarrhea is a common ear...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)recently emerged as a highly virulent respiratory pathogen that is known as the causative agent of coronavirus disease 2019(COVID-19).Diarrhea is a common early symptom in a significant proportion of patients with SARS-CoV-2 infection.SARS-CoV-2 can infect and replicate in esophageal cells and enterocytes,leading to direct damage to the intestinal epithelium.The infection decreases the level of angiotensinconverting enzyme 2 receptors,thereby altering the composition of the gut microbiota.SARS-CoV-2 elicits a cytokine storm,which contributes to gastrointestinal inflammation.The direct cytopathic effects of SARS-CoV-2,gut dysbiosis,and aberrant immune response result in increased intestinal permeability,which may exacerbate existing symptoms and worsen the prognosis.By exploring the elements of pathogenesis,several therapeutic options have emerged for the treatment of COVID-19 patients,such as biologics and biotherapeutic agents.However,the presence of SARS-CoV-2 in the feces may facilitate the spread of COVID-19 through fecal-oral transmission and contaminate the environment.Thus gastrointestinal SARS-CoV-2 infection has important epidemiological significance.The development of new therapeutic and preventive options is necessary to treat and restrict the spread of this severe and widespread infection more effectively.Therefore,we summarize the key elements involved in the pathogenesis and the epidemiology of COVID-19-associated diarrhea.展开更多
Viral hepatitis remains a significant worldwide threat,in spite of the availability of several successful therapeutic and vaccination strategies.Complications associated with acute and chronic infections,such as liver...Viral hepatitis remains a significant worldwide threat,in spite of the availability of several successful therapeutic and vaccination strategies.Complications associated with acute and chronic infections,such as liver failure,cirrhosis and hepatocellular carcinoma,are the cause of considerable morbidity and mortality.Given the significant burden on the healthcare system caused by viral hepatitis,it is essential that novel,more effective therapeutics be developed.The present review attempts to summarize the current treatments against viral hepatitis,and provides an outline for upcoming,promising new therapeutics.Development of novel therapeutics requires an understanding of the viral life cycles and viral effectors in molecular detail.As such,this review also discusses virallyencoded effectors,found to be essential for virus survival and replication in the host milieu,which may be utilized as potential candidates for development of alternative therapies in the future.展开更多
基金financial support from the National Natural Science Foundation of China(Nos.21625302,21573217 and 91430110)
文摘Protein p7 of HCV is a 63 amino acid channel forming membrane protein essential for the progression ofviral infection and the sensitivity of this channel to small-molecule inhibitors renders p7 a potentialtarget for novel therapies against HCV infection. Previous biochemical experiments suggested that theHis17 of p7 is a pore-lining residue and solvated-exposed to participate in channel gating. However, arecent NMR structural identification of the p7 hexamer in dodecylphosphocholine （DPC） micellesindicated that the His17 is embedded into the protein matrix. In this work, we performed moleculardynamic simulations to bridge the controversial observations. Our results illustrated that byincorporating the cholesterol into DOPC membranes to mimic an actual membrane-like composition,the orientation of His17 in the hexameric bundles spontaneously access to the central pore region,indicating a versatile property of the p7 viroporin conformation that could be voluntarily influenced byits surrounding environments.
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)recently emerged as a highly virulent respiratory pathogen that is known as the causative agent of coronavirus disease 2019(COVID-19).Diarrhea is a common early symptom in a significant proportion of patients with SARS-CoV-2 infection.SARS-CoV-2 can infect and replicate in esophageal cells and enterocytes,leading to direct damage to the intestinal epithelium.The infection decreases the level of angiotensinconverting enzyme 2 receptors,thereby altering the composition of the gut microbiota.SARS-CoV-2 elicits a cytokine storm,which contributes to gastrointestinal inflammation.The direct cytopathic effects of SARS-CoV-2,gut dysbiosis,and aberrant immune response result in increased intestinal permeability,which may exacerbate existing symptoms and worsen the prognosis.By exploring the elements of pathogenesis,several therapeutic options have emerged for the treatment of COVID-19 patients,such as biologics and biotherapeutic agents.However,the presence of SARS-CoV-2 in the feces may facilitate the spread of COVID-19 through fecal-oral transmission and contaminate the environment.Thus gastrointestinal SARS-CoV-2 infection has important epidemiological significance.The development of new therapeutic and preventive options is necessary to treat and restrict the spread of this severe and widespread infection more effectively.Therefore,we summarize the key elements involved in the pathogenesis and the epidemiology of COVID-19-associated diarrhea.
基金a grant from the Department of Biotechnology,India (BT/PR7439/MED/29/676/2012).D.D
文摘Viral hepatitis remains a significant worldwide threat,in spite of the availability of several successful therapeutic and vaccination strategies.Complications associated with acute and chronic infections,such as liver failure,cirrhosis and hepatocellular carcinoma,are the cause of considerable morbidity and mortality.Given the significant burden on the healthcare system caused by viral hepatitis,it is essential that novel,more effective therapeutics be developed.The present review attempts to summarize the current treatments against viral hepatitis,and provides an outline for upcoming,promising new therapeutics.Development of novel therapeutics requires an understanding of the viral life cycles and viral effectors in molecular detail.As such,this review also discusses virallyencoded effectors,found to be essential for virus survival and replication in the host milieu,which may be utilized as potential candidates for development of alternative therapies in the future.
