Liberty T Navhaya, Thabe M Matsebatlela, Mokgerwa Z Monama, Xolani H Makhoba
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引用次数: 0
Abstract
The SARS-CoV-2 spike protein is pivotal in the COVID-19 virus's life cycle, facilitating viral attachment to host cells. It is believed that targeting this viral protein could be key to developing effective COVID-19 prophylactics. Using in silico techniques, this study sought to virtually screen for compounds from the literature that strongly bind and disrupt the stability of the HSPA8-spike protein complex. To evaluate the interactions between the individual proteins and the protein complex attained from protein-protein docking using BioLuminate, molecular docking was performed using the Maestro Schrodinger Suite. The screened small molecules met all bioavailability conditions, Lipinski's and Veber's rules, and the required medicinal chemistry properties. Protein-protein docking of the spike protein and HSPA8 identified the optimal pose with a PIPER cluster size of 65, a PIPER pose energy of -748.301 kcal/mol, and a PIPER pose score of -101.189 kcal/mol. Two small molecules, NSC36398 and NSC281245, showed promising docking scores against the spike protein individually and in a complex with HSPA8. NSC36398 had a docking score of -7.934 kcal/mol and a binding free energy of -39.52 kcal/mol with the viral spike protein and a docking score of -8.029 kcal/mol and binding free energy of -38.61 with the viral protein in complex with HSPA8, respectively. Mevastatin had a docking score of -5.099 kcal/mol and a binding free energy of -44.49 kcal/mol with the viral protein and a docking score of -5.285 kcal/mol and binding free energy of -36.65 kcal/mol with the viral protein in complex with HSPA8, respectively. These results, supported by extensive 2D interaction diagrams, suggest that NSC36398 and NSC281245 are potential drug candidates targeting SARS-CoV-2 spike protein.
期刊介绍:
Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.