Higher binding affinity of Furin to SARS-CoV-2 spike (S) protein D614G could be associated with higher SARS-CoV-2 infectivity
Date
2020Author
Mohammad, Anwar
Alshawaf, Eman
Marafie, Sulaiman K
Abu-Farha, Mohamed
Abubaker, Jehad
Al-Mulla, Fahd
Metadata
Show full item recordAbstract
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 D614G mutation of SARS-CoV-2 S-protein,
which may affect viral infectivity.
Methods
The effect of D614G 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 Sprotein 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 D614G 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 D614G 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 D614G mutation
may result in a more virulent strain.
Palabras clave
SARS-CoV-2; COVID-19; Furin; S-protein; G clade; Interatomic binding; Thermodynamic stability; Molecular dynamic simulationsLink to resource
https://doi.org/10.1016/j.ijid.2020.10.033Collections
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