SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate

Abstract

Aim: The COVID-19 pandemic is caused by infection with the SARS-CoV-2 virus. The major mutation detected to date in the SARS-CoV-2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation.

Result: Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilise a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.

Conclusion: These results imply that G614 is a more pathogenic strain of SARS-CoV-2, which may influence vaccine design. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID-19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection.

FIGURE 1

A, Linear regression of average case fatality rate (CFR Average; Y‐axis) with percentage of viruses exhibiting a glycine (G) at amino acid position 614 in the viral envelope spike protein (Percentage G614; X‐axis). B, Same linear regression as A but using median CFR. C, Table of underlying data used in the regression

FIGURE 2

A, Location of D614 (CPK depiction; arrow) in viral envelope trimeric spike structure. B, Close‐up of D614 showing optimal packing with T859 in adjacent monomer helical stalk, which would result in a cavity upon mutation to G614, which has no side chain. C, Energy calculation for D to G mutation for different 3D structural conformations of the SARS‐CoV‐2 viral spike