Preprint Hypothesis Version 1 Preserved in Portico This version is not peer-reviewed

A Furin Cleavage Site Inserted into the Spike Protein of SARS-CoV-2: A Structural Implication?

Version 1 : Received: 27 March 2020 / Approved: 29 March 2020 / Online: 29 March 2020 (08:54:42 CEST)

How to cite: Li, W. A Furin Cleavage Site Inserted into the Spike Protein of SARS-CoV-2: A Structural Implication?. Preprints 2020, 2020030428 (doi: 10.20944/preprints202003.0428.v1). Li, W. A Furin Cleavage Site Inserted into the Spike Protein of SARS-CoV-2: A Structural Implication?. Preprints 2020, 2020030428 (doi: 10.20944/preprints202003.0428.v1).

Abstract

One notable features of the SARS-CoV-2 genome is that the spike protein of SARS-CoV-2 has a functional polybasic (furin) cleavage site (RRAR) at the S1–S2 boundary through the insertion of 12 nucleotides encoding PRRA. To date, the furin cleavage site (FCS) remains an experimentally uncharted territory both structurally and functionally. For instance, whether or not FCS is actually cleaved, before or after viral cell entry or exit, still remains to be experimentally investigated. With currently available structural data, this article presents a computational structural characterization of the FCS inserted into SARS-CoV-2 spike glycoprotein, and puts forward a set of structural hypothesis against the hypothesis of SARS-CoV-2 from purposeful manipulation: (1), the inserted FCS does not alter, neither stabilize nor de-stabilize, the overall structure of SARS-CoV-2 spike glycoprotein; (2), the net structural consequence of FCS is the insertion of a furin cleavage site into SARS-CoV-2 spike glycoprotein, whose S1 and S2 subunits will still be bonded together even if the FCS is actually cleaved by furin protease.

Subject Areas

COVID-19; SARS-CoV-2; furin cleavage site (FCS); salt bridging analysis

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