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Molecular characterization of interactions between the D614G variant of SARS-CoV-2 S-protein and neutralizing antibodies: A computational approach.
Infect Genet Evol. 2021 07; 91:104815.IG

Abstract

The D614G variant of SARS-CoV-2 S-protein emerged in early 2020 and quickly became the dominant circulating strain in Europe and its environs. The variant was characterized by the higher viral load, which is not associated with disease severity, higher incorporation into the virion, and high cell entry via ACE-2 and TMPRSS2. Previous strains of the coronavirus and the current SARS-CoV-2 have demonstrated the selection of mutations as a mechanism of escaping immune responses. In this study, we used molecular dynamics simulation and MM-PBSA binding energy analysis to provide insights into the behaviour of the D614G S-protein at the molecular level and describe the neutralization mechanism of this variant. Our results show that the D614G S-protein adopts distinct conformational dynamics which is skewed towards the open-state conformation more than the closed-state conformation of the wild-type S-protein. Residue-specific variation of amino acid flexibility and domain-specific RMSD suggest that the mutation causes an allosteric conformational change in the RBD. Evaluation of the interaction energies between the S-protein and neutralizing antibodies show that the mutation may enhance, reduce or not affect the neutralizing interactions depending on the neutralizing antibody, especially if it targets the RBD. The results of this study have shed insights into the behaviour of the D614G S-protein at the molecular level and provided a glimpse of the neutralization mechanism of this variant.

Authors+Show Affiliations

Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana; Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana. Electronic address: akwarteng@knust.edu.gh.Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana; Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.Department of Molecular Medicine, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana; Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33774178

Citation

Kwarteng, Alexander, et al. "Molecular Characterization of Interactions Between the D614G Variant of SARS-CoV-2 S-protein and Neutralizing Antibodies: a Computational Approach." Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases, vol. 91, 2021, p. 104815.
Kwarteng A, Asiedu E, Sylverken AA, et al. Molecular characterization of interactions between the D614G variant of SARS-CoV-2 S-protein and neutralizing antibodies: A computational approach. Infect Genet Evol. 2021;91:104815.
Kwarteng, A., Asiedu, E., Sylverken, A. A., Larbi, A., Sakyi, S. A., & Asiedu, S. O. (2021). Molecular characterization of interactions between the D614G variant of SARS-CoV-2 S-protein and neutralizing antibodies: A computational approach. Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases, 91, 104815. https://doi.org/10.1016/j.meegid.2021.104815
Kwarteng A, et al. Molecular Characterization of Interactions Between the D614G Variant of SARS-CoV-2 S-protein and Neutralizing Antibodies: a Computational Approach. Infect Genet Evol. 2021;91:104815. PubMed PMID: 33774178.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular characterization of interactions between the D614G variant of SARS-CoV-2 S-protein and neutralizing antibodies: A computational approach. AU - Kwarteng,Alexander, AU - Asiedu,Ebenezer, AU - Sylverken,Augustina Angelina, AU - Larbi,Amma, AU - Sakyi,Samuel Asamoah, AU - Asiedu,Samuel Opoku, Y1 - 2021/03/24/ PY - 2020/10/27/received PY - 2021/03/10/revised PY - 2021/03/20/accepted PY - 2021/3/29/pubmed PY - 2021/6/1/medline PY - 2021/3/28/entrez KW - D614G KW - Molecular dynamics simulation KW - Neutralizing antibody KW - S-protein KW - SARS-CoV-2 SP - 104815 EP - 104815 JF - Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases JO - Infect Genet Evol VL - 91 N2 - The D614G variant of SARS-CoV-2 S-protein emerged in early 2020 and quickly became the dominant circulating strain in Europe and its environs. The variant was characterized by the higher viral load, which is not associated with disease severity, higher incorporation into the virion, and high cell entry via ACE-2 and TMPRSS2. Previous strains of the coronavirus and the current SARS-CoV-2 have demonstrated the selection of mutations as a mechanism of escaping immune responses. In this study, we used molecular dynamics simulation and MM-PBSA binding energy analysis to provide insights into the behaviour of the D614G S-protein at the molecular level and describe the neutralization mechanism of this variant. Our results show that the D614G S-protein adopts distinct conformational dynamics which is skewed towards the open-state conformation more than the closed-state conformation of the wild-type S-protein. Residue-specific variation of amino acid flexibility and domain-specific RMSD suggest that the mutation causes an allosteric conformational change in the RBD. Evaluation of the interaction energies between the S-protein and neutralizing antibodies show that the mutation may enhance, reduce or not affect the neutralizing interactions depending on the neutralizing antibody, especially if it targets the RBD. The results of this study have shed insights into the behaviour of the D614G S-protein at the molecular level and provided a glimpse of the neutralization mechanism of this variant. SN - 1567-7257 UR - https://www.unboundmedicine.com/medline/citation/33774178/Molecular_characterization_of_interactions_between_the_D614G_variant_of_SARS_CoV_2_S_protein_and_neutralizing_antibodies:_A_computational_approach_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-1348(21)00112-X DB - PRIME DP - Unbound Medicine ER -