Abstract
Coronavirus disease 2019 (COVID-19) pandemic has been attributed to SARS-CoV-2 (SARS2) and, consequently, SARS2 has evolved into multiple SARS2 variants driving subsequent waves of infections. In particular, variants of concern (VOC) were identified to have both increased transmissibility and virulence ascribable to mutational changes occurring within the spike protein resulting to modifications in the protein structural orientation which in-turn may affect viral pathogenesis. However, this was never fully elucidated. Here, we generated spike models of endemic HCoVs (HCoV 229E, HCoV OC43, HCoV NL63, HCoV HKU1, SARS CoV, MERS CoV), original SARS2, and VOC (alpha, beta, gamma, delta). Model quality check, structural superimposition, and structural comparison based on RMSD values, TM scores, and contact mapping were all performed. We found that: 1) structural comparison between the original SARS2 and VOC whole spike protein model have minor structural differences (TM > 0.98); 2) the whole VOC spike models putatively have higher structural similarity (TM > 0.70) to spike models from endemic HCoVs coming from the same phylogenetic cluster; 3) original SARS2 S1-CTD and S1-NTD models are structurally comparable to VOC S1-CTD (TM = 1.0) and S1-NTD (TM > 0.96); and 4) endemic HCoV S1-CTD and S1-NTD models are structurally comparable to VOC S1-CTD (TM > 0.70) and S1-NTD (TM > 0.70) models belonging to the same phylogenetic cluster. Overall, we propose that structural similarities (possibly ascribable to similar conformational epitopes) may help determine immune cross-reactivity, whereas, structural differences (possibly associated with varying conformational epitopes) may lead to viral infection (either reinfection or breakthrough infection).
Highlights
Coronaviruses (CoV) are categorized as enveloped positive-stranded RNA viruses belonging to family Coronaviridae, order Nidovirales, and subfamily Othocoronavirinae comprising four genera (King et al, 2018)
Considering variants of concern (VOC) are a product of mutational changes occurring within the spike and structural orientation modifications are a product of amino acid alterations which in-turn may affect viral pathogenesis (Chen and Bahar, 2004), we hypothesize that the VOC spike glycoprotein may have structural modifications that may affect both immune cross-reactivity and viral pathogenesis
Throughout this study, we attempted to show that VOC spike models have structural similarities and differences with the original SARS2 and endemic human CoV (HCoV) spike models
Summary
Coronaviruses (CoV) are categorized as enveloped positive-stranded RNA viruses belonging to family Coronaviridae, order Nidovirales, and subfamily Othocoronavirinae comprising four genera (King et al, 2018). Considering VOC are a product of mutational changes occurring within the spike and structural orientation modifications are a product of amino acid alterations which in-turn may affect viral pathogenesis (Chen and Bahar, 2004), we hypothesize that the VOC spike glycoprotein may have structural modifications that may affect both immune cross-reactivity and viral pathogenesis. This has likewise not been fully investigated. A better understanding of the possible structural differences and similarities occurring within the VOC spike proteins may give us a better understanding of the potential of cross-reactivity to occur and, likewise, could give a possible explanation for the occurrence of both SARS2 reinfection and breakthrough infections which in-turn may lead to novel therapeutic strategies
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