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Molecular dynamics simulations of the spike trimeric ectodomain of the SARS-CoV-2 Omicron variant: structural relationships with infectivity, evasion to immune system and transmissibility.
de Souza, Anacleto Silva; Amorim, Vitor Martins de Freitas; de Souza, Robson Francisco; Guzzo, Cristiane Rodrigues.
  • de Souza AS; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Amorim VMF; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • de Souza RF; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Guzzo CR; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
J Biomol Struct Dyn ; : 1-18, 2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2106892
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron is currently the most prevalent SARS-CoV-2 variant worldwide. Herein, we calculated molecular dynamics simulations of the trimeric spikeWT and SpikeBA.1 for 300 ns. Our results show that SpikeBA.1 has more conformational flexibility than SpikeWT. Our principal component analysis (PCA) allowed us to observe a broader spectrum of different conformations for SpikeBA.1, mainly at N-terminal domain (NTD) and receptor-binding domain (RBD). Such increased flexibility could contribute to decreased neutralizing antibody recognition of this variant. Our molecular dynamics data show that the RBDBA.1 easily visits an up-conformational state and the prevalent D614G mutation is pivotal to explain molecular dynamics results for this variant because to lost hydrogen bonding interactions between the residue pairs K854SC/D614SC, Y837MC/D614MC, K835SC/D614SC, T859SC/D614SC. In addition, SpikeBA.1 residues near the furin cleavage site are more flexible than in SpikeWT, probably due to P681H and D614G substitutions. Finally, dynamical cross-correlation matrix (DCCM) analysis reveals that D614G and P681H may allosterically affect the cleavage site S1/S2. Conversely, S2' site may be influenced by residues located between NTD and RBD of a neighboring protomer of the SpikeWT. Such communication may be lost in SpikeBA.1, explaining the changes of the cell tropism in the viral infection. In addition, the movements of the NTDWT and NTDBA.1 may modulate the RBD conformation through allosteric effects. Taken together, our results explain how the structural aspects may explain the observed gains in infectivity, immune system evasion and transmissibility of the Omicron variant.Communicated by Ramaswamy H. Sarma.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Randomized controlled trials Topics: Variants Language: English Journal: J Biomol Struct Dyn Year: 2022 Document Type: Article Affiliation country: 07391102.2022.2142296

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Randomized controlled trials Topics: Variants Language: English Journal: J Biomol Struct Dyn Year: 2022 Document Type: Article Affiliation country: 07391102.2022.2142296