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ORIGINAL RESEARCH ARTICLE

Evaluating the SARS-CoV-2 spike glycoprotein as a molecular target for therapeutic development

Brandon H. Adame-Velasco1† ,  Pablo Octavio-Aguilar1* ,  Luis H. Mendoza-Huizar2† ,  Liliana M. Aguilar-Castro1†
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1 Genetics Laboratory, Biological Research Center, Autonomous University of the State of Hidalgo, Mineral de la Reforma, Hidalgo, Mexico
2 Academic Area of Chemistry, Autonomous University of the State of Hidalgo, Mineral de la Reforma, Hidalgo, Mexico
†These authors contributed equally to this work.
INNOSC Theranostics and Pharmacological Sciences 2024, 7(2), 1651 https://doi.org/10.36922/itps.1651
Submitted: 22 August 2023 | Accepted: 4 December 2023 | Published: 26 March 2024
© 2024 by the Author (s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The SARS-CoV-2 virus gains entry into host cells by binding its spike glycoprotein (S-glycoprotein) to the angiotensin 2 receptor. This viral protein contains several conserved regions, such as the receptor binding domain region, making it an ideal target for treating COVID-19. Notably, the majority of existing vaccines elicit antigenic reaction by targeting this protein epitope. This study evaluated the binding affinities of 44 different drugs against the SARS-CoV-2 S-glycoprotein, considering their toxicity profiles and previous clinical studies at different testing stages. Our results revealed that maraviroc and estradiol benzoate exhibited high affinities (−7.7 and −7.6 kcal mol−1, respectively), while other ligands, such as indinavir and ritonavir, showed affinity at lower levels. Among the drugs with high affinity, toxicity levels ranged from harmful if swallowed (300 mg/kg < LD50 < 2000 mg/kg) to non-toxic (LD50 > 5000 mg/kg), with only three having undergone clinical testing, yielding promising or controversial results. Furthermore, emtricitabine and docosanol, previously explored as COVID-19 treatments, exhibited the lowest affinities (−4.7 and −3.9 kcal mol−1, respectively), with associated harmful effects if swallowed. These results provide essential information about drug interaction against the SARS-CoV-2 S-glycoprotein and potential treatment pathways for COVID-19.

Keywords
SARS-CoV-2
Coronavirus spike glycoprotein
Molecular docking simulation
Pharmacology
Cluster MCMC
Funding
None.
Conflict of interest
The authors declare no conflicts of interest.
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INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Print ISSN: 2705-0734, Published by AccScience Publishing
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