Aim: The COVID 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 destabilize 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. What is known about this topic? Nothing is
known about the health significance of the D614G SARS-CoV-2 variant.
What does this article add? A molecular clue to viral molecular
pathogenesis of COVID-19 disease.