tetano
Editor, Senior Moderator
Int J Infect Dis
. 2020 Oct 16;S1201-9712(20)32237-2.
doi: 10.1016/j.ijid.2020.10.033. Online ahead of print.
Higher binding affinity of Furin to SARS-CoV-2 spike (S) protein D614G could be associated with higher SARS-CoV-2 infectivity
Anwar Mohammad[SUP] 1 [/SUP], Eman Alshawaf[SUP] 2 [/SUP], Sulaiman K Marafie[SUP] 2 [/SUP], Mohamed Abu-Farha[SUP] 2 [/SUP], Jehad Abubaker[SUP] 2 [/SUP], Fahd Al-Mulla[SUP] 3 [/SUP]
Affiliations
Abstract
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 (K[SUB]d[/SUB] = 1.6 ? 10[SUP]-8[/SUP]) 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.
Keywords: COVID-19; G clade; S-protein; SARS-CoV-2; furin; interatomic binding; molecular dynamic simulations; thermodynamic stability.
. 2020 Oct 16;S1201-9712(20)32237-2.
doi: 10.1016/j.ijid.2020.10.033. Online ahead of print.
Higher binding affinity of Furin to SARS-CoV-2 spike (S) protein D614G could be associated with higher SARS-CoV-2 infectivity
Anwar Mohammad[SUP] 1 [/SUP], Eman Alshawaf[SUP] 2 [/SUP], Sulaiman K Marafie[SUP] 2 [/SUP], Mohamed Abu-Farha[SUP] 2 [/SUP], Jehad Abubaker[SUP] 2 [/SUP], Fahd Al-Mulla[SUP] 3 [/SUP]
Affiliations
- PMID: 33075532
- PMCID: PMC7567667
- DOI: 10.1016/j.ijid.2020.10.033
Abstract
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 (K[SUB]d[/SUB] = 1.6 ? 10[SUP]-8[/SUP]) 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.
Keywords: COVID-19; G clade; S-protein; SARS-CoV-2; furin; interatomic binding; molecular dynamic simulations; thermodynamic stability.