AccScience Publishing / ITPS / Volume 7 / Issue 2 / DOI: 10.36922/itps.1651

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
INNOSC Theranostics and Pharmacological Sciences 2024, 7(2), 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 -Noncommercial 4.0 International License (CC-by the license) ( )

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.

Coronavirus spike glycoprotein
Molecular docking simulation
Cluster MCMC
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Conflict of interest
The authors declare no conflicts of interest.
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