Dataset Information

Molecular Level Dissection of Critical Spike Mutations in SARS-CoV-2 Variants of Concern (VOCs): A Simplified Review.

ABSTRACT: SARS-CoV-2 virus during its spread in the last one and half year has picked up critical changes in its genetic code i.e. mutations, which have leads to deleterious epidemiological characteristics. Due to critical role of spike protein in cell entry and pathogenesis, mutations in spike regions have been reported to enhance transmissibility, disease severity, possible escape from vaccine-induced immune response and reduced diagnostic sensitivity/specificity. Considering the structure-function impact of mutations, understanding the molecular details of these key mutations of newly emerged variants/lineages is of urgent concern. In this review, we have explored the literature on key spike mutations harbored by alpha, beta, gamma and delta 'variants of concern' (VOCs) and discussed their molecular consequences in the context of resultant virus biology. Commonly all these VOCs i.e. B.1.1.7, B.1.351, P.1 and B.1.617.2 lineages have decisive mutation in Receptor Binding Motif (RBM) region and/or region around Furin cleavage site (FCS) of spike protein. In general, mutation induced disruption of intra-molecular interaction enhances molecular flexibility leading to exposure of spike protein surface in these lineages to make it accessible for inter-molecular interaction with hACE2. A disruption of spike antigen-antibody inter-molecular interactions in epitope region due to the chemical nature of substituting amino acid hampers the neutralization efficacy. Simplified surveillance of mutation induced changes and their consequences at molecular level can contribute in rationalizing mutation's impact on virus biology. It is believed that molecular level dissection of these key spike mutation will assist the future investigations for a more resilient outcome against severity of COVID-19.

SUBMITTER: Joshi N

PROVIDER: S-EPMC8441688 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic agent capable of infecting humans and a wide range of animal species. Over the duration of the pandemic, mutations in the SARS-CoV-2 spike (S) protein have arisen, culminating in the spread of several variants of concern (VOCs) with various degrees of altered virulence, transmissibility, and neutralizing antibody escape. In this study, we used pseudoviruses that express specific SARS-CoV-2 S protein substitutions and cell lines that express angiotensin-converting enzyme 2 (ACE2) from nine different animal species to gain insights into the effects of VOC mutations on viral entry and antibody neutralization capability. All animal ACE2 receptors tested, except mink, support viral cell entry for pseudoviruses expressing the ancestral prototype S at levels comparable to human ACE2. Most single S substitutions did not significantly change virus entry, although 614G and 484K resulted in a decreased efficiency. Conversely, combinatorial VOC substitutions in the S protein were associated with increased entry of pseudoviruses. Neutralizing titers in sera from various animal species were significantly reduced against pseudoviruses expressing the S proteins of Beta, Delta, or Omicron VOCs compared to the parental S protein. Especially, substitutions in the S protein of the Omicron variant significantly reduced the neutralizing titers of the sera. This study reveals important insights into the host range of SARS-CoV-2 and the effect of recently emergent S protein substitutions on viral entry, virus replication, and antibody-mediated viral neutralization. IMPORTANCE The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to have devastating impacts on global health and socioeconomics. The recent emergence of SARS-CoV-2 variants of concern, which contain mutations that can affect the virulence, transmission, and effectiveness of licensed vaccines and therapeutic antibodies, are currently becoming the common strains circulating in humans worldwide. In addition, SARS-CoV-2 has been shown to infect a wide variety of animal species, which could result in additional mutations of the SARS-CoV-2 virus. In this study, we investigate the effect of mutations present in SARS-CoV-2 variants of concern and determine the effects of these mutations on cell entry, virulence, and antibody neutralization activity in humans and a variety of animals that might be susceptible to SARS-CoV-2 infection. This information is essential to understand the effects of important SARS-CoV-2 mutations and to inform public policy to create better strategies to control the COVID-19 pandemic.

Dataset Information

Molecular Level Dissection of Critical Spike Mutations in SARS-CoV-2 Variants of Concern (VOCs): A Simplified Review.

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