In silico identification of RBD subdomain of spike protein from Pro322-Thr581 for applications in vaccine development against SARS-CoV2

Nataraj S Pagadala; Abdolamir Landi; Paramahamsa Maturu; Jack Tuszynski

doi:10.1016/j.molstruc.2021.130534

In silico identification of RBD subdomain of spike protein from Pro³²²-Thr⁵⁸¹ for applications in vaccine development against SARS-CoV2

J Mol Struct. 2021 Sep 15:1240:130534. doi: 10.1016/j.molstruc.2021.130534. Epub 2021 Apr 30.

Authors

Nataraj S Pagadala¹, Abdolamir Landi², Paramahamsa Maturu³, Jack Tuszynski²

Affiliations

¹ Carnegie Mellon University, Department of Chemistry, Mellon Institute Bldg. 4400 Fifth Avenue, Pittsburgh, PA 15213-2683, United States.
² Li Ka Shing Applied Virology Institute, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada.
³ Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States.

Abstract

The three-dimensional hybrid structures of coronavirus spike proteins including the C-terminal sequence and receptor binding motif (RBM) was remodeled and energy minimized. Further, protein-protein docking show that Receptor Binding Domain (RBD) of SARS-CoV 2 Lys⁴⁵⁷-Pro⁴⁹⁰ bind on the surface of ACE2 receptor near N-terminal helices to form host-pathogen attachment. In this binding interface, SARS-CoV 2 shows a tight network of hydrogen bonds than other spike proteins from BtRsRaTG13-CoV, SARS-CoV, BtRsBeta-CoV, BtRsCoV-related, Pangolin-CoV (PCoV), human-CoV (hCoV), MERS-CoV (MCoV), Avian-CoV (ACoV) and PEDV1-CoV. Further studies show that subdomains from SARS-CoV 2 RBD Pro³²²-Thr⁵⁸¹, SARS-CoV RBD Pro³⁰⁹-Pro⁵⁷⁵, BtRsRaTG13 RBD Thr⁵⁸¹-Thr³²³, BtRsBeta-CoV RBD Ser³¹¹-Thr⁵⁶⁸, BtRsCoV-related Arg³⁰⁶-Pro⁵⁷⁵ and PCoV RBD Gln³¹⁹-Ser⁵⁸⁹ show binding conformations with ACE2 like their full-length structures of spike proteins. In addition, the subdomains MCoV RBD Gly³⁷²-Val⁶¹⁶, ACoV RBD Gly³⁷²-Val⁶¹⁶ and PEDV1-CoV RBD Ala³¹⁵-Tyr⁶⁷⁵ also binds on the surface of ACE2 similar to their full-length spike proteins. The B-Cell epitope mapping also identified main antigenic determinants predicting that these nine subdomains are highly useful in recombinant vaccine development in inducing cross neutralizing antibodies against SARS-CoV 2 spike protein and inhibits its attachment with ACE2.

Keywords: ACE2; ACoV, Avian Coronavirus; BtRsBeta-CoV, Bat Respiratory syndrome Beta Coronavirus; BtRsCoV-related, Bat Respiratory syndrome Coronavirus Related.; BtRsRaTG13-CoV, Bat Coronavirus; MCoV, MERS Coronavirus; PCoV, Pangolin coronavirus; PEDV1-CoV, Porcine epidemic diarrhea virus; SARS-COV 2; SARS-CoV 2, Severe Acute Respiratory Syndrome Coronavirus-2; SARS-CoV, Severe Acute Respiratory Syndrome Coronavirus; Spike protein; hCoV, Human Coronavirus.