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Binding of SARS-CoV-2 to Cell Receptors: A Tale of Molecular Evolution.

ABSTRACT: The magnified infectious power of the SARS-CoV-2 virus compared to its precursor SARS-CoV is intimately linked to an enhanced ability in the mutated virus to find available hydrogen-bond sites in the host cells. This characteristic is acquired during virus evolution because of the selective pressure exerted at the molecular level. We pinpoint the specific residue (in the virus) to residue (in the cell) contacts during the initial recognition and binding and show that the virus⋅⋅⋅cell interaction is mainly due to an extensive network of hydrogen bonds and to a large surface of noncovalent interactions. In addition to the formal quantum characterization of bonding interactions, computation of absorption spectra for the specific virus⋅⋅⋅cell interacting residues yields significant shifts of Δλ_max =47 and 66 nm in the wavelength for maximum absorption in the complex with respect to the isolated host and virus, respectively.

SUBMITTER: Gomez SA

PROVIDER: S-EPMC7537057 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Binding of SARS-CoV-2 to Cell Receptors: A Tale of Molecular Evolution.

Gómez Santiago A SA Rojas-Valencia Natalia N Gómez Sara S Egidi Franco F Cappelli Chiara C Restrepo Albeiro A

Chembiochem : a European journal of chemical biology 20201116 4

The magnified infectious power of the SARS-CoV-2 virus compared to its precursor SARS-CoV is intimately linked to an enhanced ability in the mutated virus to find available hydrogen-bond sites in the host cells. This characteristic is acquired during virus evolution because of the selective pressure exerted at the molecular level. We pinpoint the specific residue (in the virus) to residue (in the cell) contacts during the initial recognition and binding and show that the virus⋅⋅⋅cell interaction ...[more]

PMID: 32986926

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a wide range of hosts, including hippopotami, which are semi-aquatic mammals and phylogenetically closely related to Cetacea. In this study, we characterized the binding properties of hippopotamus angiotensin-converting enzyme 2 (hiACE2) to the spike (S) protein receptor binding domains (RBDs) of the SARS-CoV-2 prototype (PT) and variants of concern (VOCs). Furthermore, the cryo-electron microscopy (cryo-EM) structure of the SARS-CoV-2 PT S protein complexed with hiACE2 was resolved. Structural and mutational analyses revealed that L30 and F83, which are specific to hiACE2, played a crucial role in the hiACE2/SARS-CoV-2 RBD interaction. In addition, comparative and structural analysis of ACE2 orthologs suggested that the cetaceans may have the potential to be infected by SARS-CoV-2. These results provide crucial molecular insights into the susceptibility of hippopotami to SARS-CoV-2 and suggest the potential risk of SARS-CoV-2 VOCs spillover and the necessity for surveillance.ImportanceThe hippopotami are the first semi-aquatic artiodactyl mammals wherein SARS-CoV-2 infection has been reported. Exploration of the invasion mechanism of SARS-CoV-2 will provide important information for the surveillance of SARS-CoV-2 in hippopotami, as well as other semi-aquatic mammals and cetaceans. Here, we found that hippopotamus ACE2 (hiACE2) could efficiently bind to the RBDs of the SARS-CoV-2 prototype (PT) and variants of concern (VOCs) and facilitate the transduction of SARS-CoV-2 PT and VOCs pseudoviruses into hiACE2-expressing cells. The cryo-EM structure of the SARS-CoV-2 PT S protein complexed with hiACE2 elucidated a few critical residues in the RBD/hiACE2 interface, especially L30 and F83 of hiACE2 which are unique to hiACE2 and contributed to the decreased binding affinity to PT RBD compared to human ACE2. Our work provides insight into cross-species transmission and highlights the necessity for monitoring host jumps and spillover events on SARS-CoV-2 in semi-aquatic/aquatic mammals.

Project description:The spike protein determines the host-range specificity of coronaviruses. In particular, the Receptor-Binding Motif in the spike protein from SARS-CoV-2 contains the amino acids involved in molecular recognition of the host Angiotensin Converting Enzyme 2. Therefore, to understand how SARS-CoV-2 acquired its capacity to infect humans it is necessary to reconstruct the evolution of this important motif. Early during the pandemic, it was proposed that the SARS-CoV-2 Receptor-Binding Domain was acquired via recombination with a pangolin infecting coronavirus. This proposal was challenged by an alternative explanation that suggested that the Receptor-Binding Domain from SARS-CoV-2 did not originated via recombination with a coronavirus from a pangolin. Instead, this alternative hypothesis proposed that the Receptor-Binding Motif from the bat coronavirus RaTG13, was acquired via recombination with an unidentified coronavirus. And as a consequence of this event, the Receptor-Binding Domain from the pangolin coronavirus appeared as phylogenetically closer to SARS-CoV-2. Recently, the genomes from coronaviruses from Cambodia (bat_RShST182/200) and Laos (BANAL-20-52/103/247) which are closely related to SARS-CoV-2 were reported. However, no detailed analysis of the evolution of the Receptor-Binding Motif from these coronaviruses was reported. Here we revisit the evolution of the Receptor-Binding Domain and Motif in the light of the novel coronavirus genome sequences. Specifically, we wanted to test whether the above coronaviruses from Cambodia and Laos were the source of the Receptor-Binding Domain from RaTG13. We found that the Receptor-Binding Motif from these coronaviruses is phylogenetically closer to SARS-CoV-2 than to RaTG13. Therefore, the source of the Receptor-Binding Domain from RaTG13 is still unidentified. In accordance with previous studies, our results are consistent with the hypothesis that the Receptor-Binding Motif from SARS-CoV-2 evolved by vertical inheritance from a bat-infecting population of coronaviruses.

Dataset Information

Binding of SARS-CoV-2 to Cell Receptors: A Tale of Molecular Evolution.

Publications

Binding of SARS-CoV-2 to Cell Receptors: A Tale of Molecular Evolution.

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