Highlights d Cryo-EM structure of SARS-CoV-2 nsp12-nsp7-nsp8 core polymerase complex d The core complex of SARS-CoV-2 has lower enzymatic activity than SARS-CoV d SARS-CoV-2 nsp7-8-12 subunits are less thermostable than the SARS-CoV counterpart
The 2015-2016 outbreak of Zika virus (ZIKV) disease has affected many countries and is a major public health concern. ZIKV is associated with fetal microcephaly and neurological complications, and countermeasures are needed to treat and prevent ZIKV infection. We report the isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV. Two of the isolated antibodies (Z23 and Z3L1) demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of dengue virus, the closest relative to ZIKV. These two antibodies provided postexposure protection to mice in vivo. Structural studies revealed that Z23 and Z3L1 bound to tertiary epitopes in envelope protein domain I, II, or III, indicating potential targets for ZIKV-specific therapy. Our results suggest the potential of antibody-based therapeutics and provide a structure-based rationale for the design of future ZIKV-specific vaccines.
Graphical Abstract Highlights d CRISPR screening identified FcRn as an essential and universal EV-B receptor d FcRn facilitates EV-B uncoating and CD55 for attachment d High-resolution Cryo-EM structures described the mechanism of virus entry d The molecular mechanism of dual (attachment versus uncoating) receptor-usage was illustrated SUMMARY a structural basis for understanding the mechanisms of enterovirus entry.
Highlights d Cryo-EM structure of the icosahedrally averaged ASFV capsid described at 4.6-Å d ASFV capsid comprises 8,280 major capsid protein p72 and 60 penton protein copies d At least three different minor proteins stabilize capsid by gluing neighboring capsomers d ASFV differs from other NCLDVs in multilayered structure and icosahedral morphology
The severe acute respiratory syndrome virus 2 (SARS-CoV-2) invades host cells by interacting with receptors/co-receptors, as well as other co-factors, via its spike (S) protein that further mediates the fusion between viral and cellular membranes. The host membrane protein angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 and a critical determinant for its cross-species transmission. Additionally, some auxiliary receptors and co-factors are also involved which would expand the host/tissue tropism of SARS-CoV-2. After receptor engagement, certain proteases are required to cleave the S protein to trigger its fusogenic activity. In this review, we discuss the recent advancement in understanding the molecular events during SARS-CoV-2 entry which would contribute to developing vaccines and therapeutics.
Favipiravir inhibits viral replication mainly by inducing mutations -Structure of Favipiravir bound to SARS-CoV-2 polymerase in the pre-catalytic state -The structure reveals the base-pairing pattern of Favipiravir to pyrimidine residues ll www.cell.com/the-innovation
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