Cryo-EM structure of SARS-CoV spike glycoprotein in post-fusion state

Subjects: Biology >> Virology submitted time 2020-03-06

Fan, Xiaoyi Cao, Duanfang Kong, Lingfei Zhang, Xinzheng

Abstract： Global emergencies caused by the zoonotic severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the newly discovered 2019 novel coronavirus (2019-nCoV) have posed a serious threat to human health. The spike (S) glycoprotein, a homotrimer located on the surface of the viral envelope, is the key antigen for therapeutic development. The S2 subunit from the S glycoprotein, which is highly conserved among coronaviruses, contributes to viral entry by mediating the host-viral membrane fusion. However, the structural information of the post-fusion S2 machinery from these highly pathogenic human-infecting coronaviruses is still lacking. Here, we report the structure of SARS-CoV S glycoprotein in the post-fusion state by single particle cryo-electron microscopy, revealing a more rotated HR1-HR2 six-helix bundle and a tightly bound linker region upstream of the HR2 motif that plays an important role in membrane fusion. Comparison with the structure of pre-fusion SARS-CoV S glycoprotein shows dramatic structural rearrangements and conformational changes, resembling that of the Mouse hepatitis virus (MHV) and other class I viral fusion proteins. By analyzing the structural features, describing the glycan shield and mapping the antibody and inhibitor targets on the surface of the post-fusion S glycoprotein, we provide structural basis of potential therapeutic targets within the highly conserved S2 subunit, which may help the development of effective vaccines and therapies against a wide range of SARS-like coronaviruses. " "

Peer Review Status:Awaiting Review

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