Abstract
Coronaviruses (CoV) are enveloped positive-stranded RNA viruses and, historically, there are seven known human-infecting CoVs with varying degrees of virulence. CoV attachment to the host is the first step of viral pathogenesis and mainly relies on the spike glycoprotein located on the viral surface. Among the human-infecting CoVs, only the infection of SARS CoV 2 (SARS2) among humans resulted to a pandemic which would suggest that the protein structural conformation of SARS2 spike protein is distinct as compared to other human-infecting CoVs. Surprisingly, the possible differences and similarities in the protein structural conformation between the various human-infecting CoV spike proteins have not been fully elucidated. In this study, we utilized a computational approach to generate models and analyze the seven human-infecting CoV spike proteins, namely: HCoV 229E, HCoV OC43, HCoV NL63, HCoV HKU1, SARS CoV, MERS CoV, and SARS2. Model quality assessment of all CoV models generated, structural superimposition of the whole protein model and selected S1 domains (S1-CTD and S1-NTD), and structural comparison based on RMSD values, Tm scores, and contact mapping were all performed. We found that the structural orientation of S1-CTD is a potential structural feature associated to both the CoV phylogenetic cluster and lineage. Moreover, we observed that spike models in the same phylogenetic cluster or lineage could potentially have similar protein structure. Additionally, we established that there are potentially three distinct S1-CTD orientation (Pattern I, Pattern II, Pattern III) among the human-infecting CoVs. Furthermore, we postulate that human-infecting CoVs in the same phylogenetic cluster may have similar S1-CTD and S1-NTD structural orientation. Taken together, we propose that the SARS2 spike S1-CTD follows a Pattern III orientation which has a higher degree of similarity with SARS1 and some degree of similarity with both OC43 and HKU1 which coincidentally are in the same phylogenetic cluster and lineage, whereas, the SARS2 spike S1-NTD has some degree of similarity among human-infecting CoVs that are either in the same phylogenetic cluster or lineage.
Highlights
Coronaviruses (CoV) are enveloped positive-stranded RNA viruses that belong to the family Coronaviridae and order Nidovirales with the subfamily Othocoronavirinae composed of four genera, namely: alphacoronavirus, betacoronavirus, gammacoronavirus, and deltacoronavirus [1]
We found that Root Mean Square Deviation (RMSD) values between crystal model:crystal [RMSD 1.78] (Figure 1D) and sequence model:crystal model [RMSD 1.77] (Figure 1E) were relatively close, which would imply that both generated models are structurally similar
severe acute respiratory syndrome (SARS)-CoV 2 (SARS2) is the causative agent of coronavirus disease 2019 (COVID-19) pandemic [19]
Summary
Coronaviruses (CoV) are enveloped positive-stranded RNA viruses that belong to the family Coronaviridae and order Nidovirales with the subfamily Othocoronavirinae composed of four genera, namely: alphacoronavirus, betacoronavirus, gammacoronavirus, and deltacoronavirus [1]. CoVs have the largest genome among all known RNA viruses which in-turn is packed in a helical capsid comprised of a nucleocapsid protein (N) and surrounded by a viral envelope which in-turn is associated with structural proteins, namely: membrane, envelope, and spike [10]. The spike protein has been involved in mediating viral entry, determinant of host tropism, inducing viral pathogenesis, and major inducer of host immune responses [9,10,11,12]. This would highlight the significance of the CoV spike protein in terms of viral pathogenesis
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