Omicron (BA.1) and Sub‐Variants (BA.1.1, BA.2 and BA.3) of SARS‐CoV‐2 Spike Infectivity and Pathogenicity: A Comparative Sequence and Structural‐based Computational Assessment

alexandrossfakianakis shared this article with you from Inoreader Omicron (BA.1) and Sub‐Variants (BA.1.1, BA.2 and BA.3) of SARS‐CoV‐2 Spike Infectivity and Pathogenicity: A Comparative Sequence and Structural‐based Computational Assessment via Journal of Medical Virology ABSTRACT The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron's receptor-binding domain and sub-variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub-variants are predicted to be deleterious. Due to the major effect of the mutations characterising in the receptor-binding domain (RBD), we found that Omicron and sub-variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and negative electrostatic surface potential human angiotensin-converting enzy me 2 (hACE2). Omicron and sub-variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild type. Negative electrostatic potential of NTD value indicates that the Omicron variant binds receptors less efficiently than the Wild type. Given that at least one receptor is highly expressed in lung and bronchial cells, the electrostatic potential of NTD negative value could be one of the factors contributing to why the Omicron variant is thought to be less harmful to the lower respiratory tract. Among Omicron sub-lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub-variant mutations at Receptor-binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N. This article is protected by copyright. All rights reserved. View on Web

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