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Assessment of mutations on RBD in the Spike protein of SARS-CoV-2 Alpha, Delta and Omicron variants.
Sci Rep. 2022 May 20; 12(1):8540.SR

Abstract

The severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2) variant Omicron spread more rapid than the other variants of SARS-CoV-2 virus. Mutations on the Spike (S) protein receptor-binding domain (RBD) are critical for the antibody resistance and infectivity of the SARS-CoV-2 variants. In this study, we have used accelerated molecular dynamics (aMD) simulations and free energy calculations to present a systematic analysis of the affinity and conformational dynamics along with the interactions that drive the binding between Spike protein RBD and human angiotensin-converting enzyme 2 (ACE2) receptor. We evaluate the impacts of the key mutation that occur in the RBDs Omicron and other variants in the binding with the human ACE2 receptor. The results show that S protein Omicron has stronger binding to the ACE2 than other variants. The evaluation of the decomposition energy per residue shows the mutations N440K, T478K, Q493R and Q498R observed in Spike protein of SARS-CoV-2 provided a stabilization effect for the interaction between the SARS-CoV-2 RBD and ACE2. Overall, the results demonstrate that faster spreading of SARS-CoV-2 Omicron may be correlated with binding affinity of S protein RBD to ACE2 and mutations of uncharged residues to positively charged residues such as Lys and Arg in key positions in the RBD.

Authors+Show Affiliations

Laboratório de Planejamento e Desenvolvimento de Fármacos, Universidade Federal do Pará, Rua Augusto Correa S/N, Belém, PA, Brazil.Laboratório de Planejamento e Desenvolvimento de Fármacos, Universidade Federal do Pará, Rua Augusto Correa S/N, Belém, PA, Brazil.Laboratório de Planejamento e Desenvolvimento de Fármacos, Universidade Federal do Pará, Rua Augusto Correa S/N, Belém, PA, Brazil.Laboratório de Planejamento e Desenvolvimento de Fármacos, Universidade Federal do Pará, Rua Augusto Correa S/N, Belém, PA, Brazil. lameira@ufpa.br.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35595778

Citation

da Costa, Clauber Henrique Souza, et al. "Assessment of Mutations On RBD in the Spike Protein of SARS-CoV-2 Alpha, Delta and Omicron Variants." Scientific Reports, vol. 12, no. 1, 2022, p. 8540.
da Costa CHS, de Freitas CAB, Alves CN, et al. Assessment of mutations on RBD in the Spike protein of SARS-CoV-2 Alpha, Delta and Omicron variants. Sci Rep. 2022;12(1):8540.
da Costa, C. H. S., de Freitas, C. A. B., Alves, C. N., & Lameira, J. (2022). Assessment of mutations on RBD in the Spike protein of SARS-CoV-2 Alpha, Delta and Omicron variants. Scientific Reports, 12(1), 8540. https://doi.org/10.1038/s41598-022-12479-9
da Costa CHS, et al. Assessment of Mutations On RBD in the Spike Protein of SARS-CoV-2 Alpha, Delta and Omicron Variants. Sci Rep. 2022 May 20;12(1):8540. PubMed PMID: 35595778.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of mutations on RBD in the Spike protein of SARS-CoV-2 Alpha, Delta and Omicron variants. AU - da Costa,Clauber Henrique Souza, AU - de Freitas,Camila Auad Beltrão, AU - Alves,Cláudio Nahum, AU - Lameira,Jerônimo, Y1 - 2022/05/20/ PY - 2022/2/27/received PY - 2022/5/3/accepted PY - 2022/5/20/entrez PY - 2022/5/21/pubmed PY - 2022/5/25/medline SP - 8540 EP - 8540 JF - Scientific reports JO - Sci Rep VL - 12 IS - 1 N2 - The severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2) variant Omicron spread more rapid than the other variants of SARS-CoV-2 virus. Mutations on the Spike (S) protein receptor-binding domain (RBD) are critical for the antibody resistance and infectivity of the SARS-CoV-2 variants. In this study, we have used accelerated molecular dynamics (aMD) simulations and free energy calculations to present a systematic analysis of the affinity and conformational dynamics along with the interactions that drive the binding between Spike protein RBD and human angiotensin-converting enzyme 2 (ACE2) receptor. We evaluate the impacts of the key mutation that occur in the RBDs Omicron and other variants in the binding with the human ACE2 receptor. The results show that S protein Omicron has stronger binding to the ACE2 than other variants. The evaluation of the decomposition energy per residue shows the mutations N440K, T478K, Q493R and Q498R observed in Spike protein of SARS-CoV-2 provided a stabilization effect for the interaction between the SARS-CoV-2 RBD and ACE2. Overall, the results demonstrate that faster spreading of SARS-CoV-2 Omicron may be correlated with binding affinity of S protein RBD to ACE2 and mutations of uncharged residues to positively charged residues such as Lys and Arg in key positions in the RBD. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/35595778/Assessment_of_mutations_on_RBD_in_the_Spike_protein_of_SARS_CoV_2_Alpha_Delta_and_Omicron_variants_ DB - PRIME DP - Unbound Medicine ER -