Abstract: Journal Pre-proofs Original article Docking and molecular dynamics studies of human ezrin protein with a mod‐ elled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors Selvaa Kumar Chellasamy, Eleanor Watson PII: DOI: Reference: S1018-3647(22)00458-X https://doi.org/10.1016/j.jksus.2022.102277 JKSUS 102277 To appear in: Journal of King Saud University - Science Received Date: Revised Date: Accepted Date: 16 June 2021 1 August 2022 8 August 2022 Please cite this article as: S.K. Chellasamy, E. Watson, Docking and molecular dynamics studies of human ezrin protein with a modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors, Journal of King Saud University - Science (2022), doi: https://doi.org/10.1016/j.jksus.2022.102277 This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2022 Published by Elsevier B.V. on behalf of King Saud University. Docking and molecular dynamics studies of human ezrin protein with a modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors Selvaa Kumar Chellasamy 1*, and Eleanor Watson 2,* School of Biotechnology and Bioinformatics, D. Y. Patil Deemed to be University, Sector-15, CBD Belapur, Navi Mumbai, 400614, India; e-mail: selvaakumar.c@dypatil.edu 2 School of Computing & Engineering, University of Gloucestershire; e-mail: eleanorwatson@connect.glos.ac.uk * Correspondence: e-mails: selvaakumar.c@dypatil.edu (SKC); Tel.: +91-022-68797900 (SKC) and eleanorwatson@connect.glos.ac.uk (EW) available at Nell Watson Ltd, c/o Mills Pyatt, 11 Kingfisher Business Park, Arthur Street, Redditch, Worcestershire, B98 8LG, United Kingdom 1 Declaration of Interests: None. Docking and molecular dynamics studies of human ezrin protein with a modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors Abstract: Human ezrin protein interacts with SARS-CoV S endodomain and restrict the virus fusion, entry, and their early events of infection. In general, their binding strength and their structural stability determines their entry into the host cells. However, the binding affinity of these two endodomains with the ezrin protein has been elusive due to a paucity of knowledge on the 3D structure. This study modelled the endodomains of both SARS-CoV-1 and SARS-CoV-2 and then docked these models with human ezrin protein. This study establishes that the modelled endodomains of both SARS-CoV-1 and SARS-Cov-2 consisted of three disulphide bridges for selfstabilization. Protein-protein docking listed four salt bridges with a higher buried surface area between ezrin-SARS-CoV-1 endodomain compared to that of ezrin-SARS-CoV-2 with six salt bridges with lower buried surface area. Molecular simulation of the ezrin-SARS-CoV-1 endodomain showed better structural stability with lower Root Mean Square Deviation score compared to that of ezrin-SARS-CoV-2 endodomain due to the substitution of Alanine with..