LAUSR

Objective The coronavirus disease-19 (COVID-19) pandemic has caused an exponential rise in death rates and hospitalizations. The aim of this study was to characterize the D614 G mutation of SARS-CoV-2 S-protein, which may affect viral infectivity. Methods The effect of D614 G mutation on the structure and thermodynamic stability of S-protein was analyzed using DynaMut and SCooP. HDOCK and PRODIGY were used to model furin protease binding to the S-protein RARR cleavage site and calculate binding affinities. Molecular dynamic (MD) simulations were used to predict S-protein apo structure, S-protein–furin complex structure, and the free binding energy of the complex. Results The D614 G mutation in the G clade of SARS-CoV-2 strains introduced structural mobility and decreased thermal stability of S-protein (ΔΔG: −0.086 kcal/mol). The mutation resulted in a stronger binding affinity (Kd = 1.6 × 10−8) to furin which may enhance S-protein cleavage. Results were corroborated by MD simulations demonstrating higher binding energy of furin to S-protein D614 mutant (−61.9 kcal/mol compared with -56.78 kcal/mol for wild-type S-protein). Conclusions The D614 G mutation in the G clade induced the flexibility of S-protein, resulting in increased furin binding which may enhance S-protein cleave and infiltration of host cells. As such, SARS-CoV-2 D614 G mutation may result in a more virulent strain.