Natural Polymorphisms Are Present in the Furin Cleavage Site of the SARS-CoV-2 Spike Glycoprotein.

Yue Xing,Qunfeng Dong,Xiao Li,Xiang Gao

doi:10.3389/fgene.2020.00783

Yue Xing, Qunfeng Dong + Show 2 more

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https://doi.org/10.3389/fgene.2020.00783

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Abstract

The furin cleavage site in the spike glycoprotein of the SARS-CoV-2 coronavirus is considered important for the virus to enter the host cells. By analyzing 45828 SARS-CoV-2 genome sequences, we identified 103 strains of SARS-CoV-2 with various DNA mutations including 18 unique non-synonymous point mutations, one deletion, and six gains of premature stop codon that may affect the furin cleavage site. Our results revealed that the furin cleavage site might not be required for SARS-CoV-2 to enter human cells in vivo. The identified mutants may represent a new subgroup of SARS-CoV-2 coronavirus with reduced tropism and transmissibility as potential live-attenuated vaccine candidates.

Highlights

A notable feature of the SARS-CoV-2 coronavirus is that its spike glycoprotein contains a polybasic furin cleavage site at the S1-S2 boundary (Andersen et al, 2020; Walls et al, 2020)
1https://www.ncbi.nlm.nih.gov/Class/Structure/aa/aa_explorer.cgi carried various DNA mutations including 25 unique ones that may affect the furin cleavage site located at the amino acid residual positions 680–689 (S1/S2 region) (Coutard et al, 2020; Wang et al, 2020; Zhang et al, 2020) of the SARS-CoV-2 spike protein (Figure 1, Table 1, and Supplementary Table 1)
96 SARS-CoV-2 strains were identified to carry a total of 23 unique point mutations in the furin cleavage site

Summary

Introduction

A notable feature of the SARS-CoV-2 coronavirus is that its spike glycoprotein contains a polybasic furin cleavage site at the S1-S2 boundary (Andersen et al, 2020; Walls et al, 2020). Due to the wide expression of furin in multiple tissues, the existence of the furin cleavage site in the spike glycoprotein may expand tropism and enhance the transmissibility of SARS-CoV-2 (Walls et al, 2020). We sought to answer a straightforward yet important question: are there any natural polymorphisms in the furin cleavage site of the SARS-CoV-2 spike glycoprotein? The existence of natural polymorphisms in the furin cleavage site may represent a new subgroup of SARS-CoV-2 coronavirus with different tropism and transmissibility We sought to answer a straightforward yet important question: are there any natural polymorphisms in the furin cleavage site of the SARS-CoV-2 spike glycoprotein? The existence of natural polymorphisms in the furin cleavage site may represent a new subgroup of SARS-CoV-2 coronavirus with different tropism and transmissibility

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