Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and...Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.展开更多
Human rhinoviruses(HRVs)are the predominant infectious agents for the common cold worldwide.The HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma.3C protease,a h...Human rhinoviruses(HRVs)are the predominant infectious agents for the common cold worldwide.The HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma.3C protease,a highly conserved enzyme,cleaves the viral polyprotein during replication and assists the virus in escaping the host immune system.These key roles make 3C protease an important drug target.A few structures of 3Cs complexed with an irreversible inhibitor rupintrivir have been determined.These structures shed light on the determinants of drug specificity.Here we describe the structures of HRV-C153C in free and inhibitor-bound forms.The volume-decreased S1'subsite and half-closed S2 subsite,which were thought to be unique features of enterovirus A 3C proteases,appear in the HRV-C 3C protease.Rupintrivir assumes an“intermediate”conformation in the complex,which might open up additional avenues for the design of potent antiviral inhibitors.Analysis of the features of the three-dimensional structures and the amino acid sequences of 3C proteases suggest new applications for existing drugs.展开更多
基金supported by the Strategic Priority Research Program (XDB29010000)National Key Research and Development Program (2018YFA0900801)+5 种基金National Science Foundation Grants 32200135 and 12034006supported by National Science Fund for Distinguished Young Scholar (No.32325004)the NSFS Innovative Research Group (No.81921005)supported by the Young Elite Scientists Sponsorship Program by CAST (2022QNRC001)the Youth Innovation Promotion Association of CAS grantsupported by the Special Research Assistant Project of the Chinese Academy of Sciences.
文摘Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.
基金supported by the National Key Research and Development Program(2018YFA0900801)National Science Foundation of China(31800145)+1 种基金the State Key Laboratory of Veterinary Etiological Biology,Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences and the seed Foundation of Innovation and Creation for Graduate Students in Northwestern Polytechnical University ZZ2019279sponsored by the Youth Innovation Promotion Association at the Chinese Academy of Sciences。
文摘Human rhinoviruses(HRVs)are the predominant infectious agents for the common cold worldwide.The HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma.3C protease,a highly conserved enzyme,cleaves the viral polyprotein during replication and assists the virus in escaping the host immune system.These key roles make 3C protease an important drug target.A few structures of 3Cs complexed with an irreversible inhibitor rupintrivir have been determined.These structures shed light on the determinants of drug specificity.Here we describe the structures of HRV-C153C in free and inhibitor-bound forms.The volume-decreased S1'subsite and half-closed S2 subsite,which were thought to be unique features of enterovirus A 3C proteases,appear in the HRV-C 3C protease.Rupintrivir assumes an“intermediate”conformation in the complex,which might open up additional avenues for the design of potent antiviral inhibitors.Analysis of the features of the three-dimensional structures and the amino acid sequences of 3C proteases suggest new applications for existing drugs.
