Page 104 - ITPS-7-2

INNOSC Theranostics

and Pharmacological Sciences

ORIGINAL RESEARCH ARTICLE
Evaluating the SARS-CoV-2 spike glycoprotein as

a molecular target for therapeutic development

1†
Brandon H. Adame-Velasco , Pablo Octavio-Aguilar *,
1
Luis H. Mendoza-Huizar , and Liliana M. Aguilar-Castro 1†
2†
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

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
† These authors contributed equally stages. Our results revealed that maraviroc and estradiol benzoate exhibited
−1
to this work. high affinities (−7.7 and −7.6 kcal mol , respectively), while other ligands, such
as indinavir and ritonavir, showed affinity at lower levels. Among the drugs with
*Corresponding author:
Pablo Octavio-Aguilar high affinity, toxicity levels ranged from harmful if swallowed (300 mg/kg < LD50
(pablo_aguilar9900@uaeh.edu.mx) < 2000 mg/kg) to non-toxic (LD50 > 5000 mg/kg), with only three having undergone
Citation: Adame-Velasco BH, clinical testing, yielding promising or controversial results. Furthermore, emtricitabine
Octavio-Aguilar P, Mendoza-Huizar and docosanol, previously explored as COVID-19 treatments, exhibited the lowest
LH, Aguilar-Castro LM. Evaluating affinities (−4.7 and −3.9 kcal mol , respectively), with associated harmful effects if
−1
the SARS-CoV-2 spike glycoprotein
as a molecular target for swallowed. These results provide essential information about drug interaction against
therapeutic development. INNOSC the SARS-CoV-2 S-glycoprotein and potential treatment pathways for COVID-19.
Theranostics and Pharmacological
Sciences. 2024;7(2):1651.
doi: 10.36922/itps.1651 Keywords: SARS-CoV-2; Coronavirus spike glycoprotein; Molecular docking simulation;
Received: August 22, 2023 Pharmacology; Cluster MCMC
Accepted: December 4, 2023
Published Online: March 26, 2024
Copyright: © 2024 Author(s). 1. Introduction
This is an Open-Access article
distributed under the terms of the On March 11, 2020, the World Health Organization declared COVID-19, caused
Creative Commons Attribution by the SARS-CoV-2 virus, a pandemic due to its rapid spread. This virus belongs to
License, permitting distribution, the Coronaviridae family, Coronavirinae subfamily, and Betacoronavirus genus.
and reproduction in any medium,
provided the original work is Coronaviruses derived their name from the multiple spikes (S-glycoproteins)
properly cited. surrounding their spherical lipoprotein capsule, giving them a crown-like appearance,
1,2
Publisher’s Note: AccScience which is recognized by receptor proteins on host cells susceptible to infection. The
Publishing remains neutral with S-glycoprotein is responsible for the attachment of the virus to host cells through
regard to jurisdictional claims in
published maps and institutional angiotensin-converting enzyme 2 (ACE2), followed by binding to the transmembrane
3,4
affiliations serine protease 2 (TMPRSS2), which allows cell membrane fusion and viral entry. On

Volume 7 Issue 2 (2024) 1 doi: 10.36922/itps.1651