Molecular switches regulating the potency and immune evasiveness of SARS-CoV-2 spike protein

Yushun Wan; Linfen Huang; Xiujuan Zhang; Jian Shang; Stanley Perlman; Lanying Du; Fang Li

doi:10.21203/rs.3.rs-736159/v2

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Molecular switches regulating the potency and immune evasiveness of SARS-CoV-2 spike protein

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Open access

Molecular switches regulating the potency and immune evasiveness of SARS-CoV-2 spike protein

Yushun Wan, Linfen Huang, Xiujuan Zhang, Jian Shang, Stanley Perlman, Lanying Du and Fang Li

Research square

10/01/2021

DOI: 10.21203/rs.3.rs-736159/v2

PMCID: PMC8491847

PMID: 34611654

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https://doi.org/10.21203/rs.3.rs-736159/v2View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

SARS-CoV-2 spike protein plays a key role in viral entry and host immune responses. The conformation of the spike protein can be either open or closed, yet it is unclear how the conformations affect the protein’s functions or what regulate the conformational changes. Using SARS-CoV-1 and bat RaTG13-CoV as comparisons, we identified two molecular switches that regulate the conformations of SARS-CoV-2 spike protein: (i) a furin motif loop turns SARS-CoV-2 spike from a closed conformation to a mixture of open and closed conformations, and (ii) a K417V mutation turns SARS-CoV-2 spike from mixed conformations to an open conformation. We showed that the open conformation favors viral potency by exposing the RBD for receptor binding and viral entry, whereas the closed conformation supports viral immune evasion by hiding the RBD from neutralizing antibodies. Hence SARS-CoV-2 spike has evolved to reach a balance between potency and immune evasiveness, which may contribute to the pandemic spread of SARS-CoV-2. The dynamics between viral potency and invasiveness is likely to further evolve, providing insights into future evolution of SARS-CoV-2.

Cell Biology

Immune System

Mutation

Antibody

biochemical phenomena, metabolism, and nutrition

fungi

Furin

Molecular switch

Potency

respiratory tract diseases

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

skin and connective tissue diseases

Viral entry

virus diseases

viruses

Details

Title: Subtitle: Molecular switches regulating the potency and immune evasiveness of SARS-CoV-2 spike protein
Creators: Yushun Wan
Linfen Huang - University of Minnesota System
Xiujuan Zhang
Jian Shang - University of Minnesota System
Stanley Perlman - University of Iowa
Lanying Du
Fang Li - University of Minnesota System
Resource Type: Preprint
Publication Details: Research square
DOI: 10.21203/rs.3.rs-736159/v2
PMID: 34611654
PMCID: PMC8491847
Language: English
Date posted: 10/01/2021
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9984530271302771

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