Higher binding affinity of furin for SARS-CoV-2 spike (S) protein D614G mutant could be associated with higher SARS-CoV-2 infectivity.
Int J Infect Dis
; 103: 611-616, 2021 Feb.
Article
in English
| MEDLINE | ID: covidwho-1039365
ABSTRACT
OBJECTIVE:
The coronavirus disease 2019 (COVID-19) pandemic has caused an exponential rise in death rates and hospitalizations. The aim of this study was to characterize the D614G substitution in the severe acute respiratory syndome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S protein), which may affect viral infectivity.METHODS:
The effect of D614G substitution on the structure and thermodynamic stability of the S protein was analyzed with use of DynaMut and SCooP. HDOCK and PRODIGY were used to model furin protease binding to the S protein RRAR cleavage site and calculate binding affinities. Molecular dynamics simulations were used to predict the S protein apo structure, the S protein-furin complex structure, and the free binding energy of the complex.RESULTS:
The D614G substitution in the G clade of SARS-CoV-2 strains introduced structural mobility and decreased the thermal stability of the S protein (ΔΔG = -0.086 kcal mol-1). The substitution resulted in stronger binding affinity (Kd = 1.6 × 10-8) for furin, which may enhance S protein cleavage. The results were corroborated by molecular dynamics simulations demonstrating higher binding energy of furin and the S protein D614G mutant (-61.9 kcal mol-1 compared with -56.78 kcal mol-1 for wild-type S protein).CONCLUSIONS:
The D614G substitution in the G clade induced flexibility of the S protein, resulting in increased furin binding, which may enhance S protein cleavage and infiltration of host cells. Therefore, the SARS-CoV-2 D614G substitution may result in a more virulent strain.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Furin
/
Mutant Proteins
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Int J Infect Dis
Journal subject:
Communicable Diseases
Year:
2021
Document Type:
Article
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