Inhibitory activity of FDA-approved drugs cetilistat, abiraterone, diiodohydroxyquinoline, bexarotene, remdesivir, and hydroxychloroquine on COVID-19 main protease and human ACE2 receptor: A comparative in silico approach - PubMed (original) (raw)

Inhibitory activity of FDA-approved drugs cetilistat, abiraterone, diiodohydroxyquinoline, bexarotene, remdesivir, and hydroxychloroquine on COVID-19 main protease and human ACE2 receptor: A comparative in silico approach

Nahid Shahabadi et al. Inform Med Unlocked. 2021.

Abstract

By September 1, 2021, SARS-CoV-2, a respiratory virus that prompted Coronavirus Disease in 2019, had infected approximately 218,567,442 patients and claimed 4,534,151 lives. There are currently no specific treatments available for this lethal virus, although several drugs, including remdesivir and hydroxychloroquine, have been tested. The purpose of this study is to assess the activity of FDA-approved drugs cetilistat, abiraterone, diiodohydroxyquinoline, bexarotene, remdesivir, and hydroxychloroquine as potential SARS-CoV-2 main protease inhibitors. Additionally, this study aims to provide insight into the development of potential inhibitors that may inhibit ACE2, thereby preventing SARS-CoV-2 entry into the host cell and infection. To this end, remdesivir and hydroxychloroquine were used as comparator drugs. The calculations revealed that cetilistat, abiraterone, diiodohydroxyquinoline, and bexarotene inhibit main protease and ACE2 receptors more effectively than the well-known drug hydroxychloroquine when used against COVID-19. Meanwhile, bexarotene and cetilistat bind more tightly to the SARS-CoV-2 main protease and the ACE2 receptor, respectively, than remdesivir, a potential treatment for COVID-19 that is the first FDA-approved drug against this virus. As a result, the molecular dynamic simulations of these two drugs in the presence of proteins were investigated. The MD simulation results demonstrated that these drugs interact to stabilize the systems, allowing them to be used as effective inhibitors of these proteins. Meanwhile, bexarotene, abiraterone, cetilistat, and diiodohydroxyquinoline's systemic effects should be further investigated in suitable ex vivo human organ culture or organoids, animal models, or clinical trials.

Keywords: ACE2 receptor; COVID-19; Dynamic simulation; Main protease; Molecular docking.

© 2021 Published by Elsevier Ltd.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1

Graphical abstract

Fig. 1

Fig. 1

Molecular docking perspective of abiraterone – (ACE2-RBD).

Fig. 2

Fig. 2

Molecular docking perspective of bexarotene – (ACE2-RBD).

Fig. 3

Fig. 3

Molecular docking perspective of cetilistat – (ACE2-RBD).

Fig. 4

Fig. 4

Molecular docking perspective of diiodohydroxyquinoline – (ACE2-RBD).

Fig. 5

Fig. 5

Molecular docking perspective of remdesivir – (ACE2-RBD).

Fig. 6

Fig. 6

Molecular docking perspective of hydroxychloroquine – (ACE2-RBD).

Fig. 7

Fig. 7

Radius of gyration (Rg) for (A) bexarotene – CoV-2 main protease and (B) cetilistat – (ACE2-RBD) during 30 ns MD simulation.

Fig. 8

Fig. 8

RMSD plots for (A) bexarotene – CoV-2 main protease and (B) cetilistat – (ACE2-RBD) during 30 ns MD simulation.

Fig. 9

Fig. 9

RMSF plots for (A) bexarotene – CoV-2 main protease and (B) cetilistat – (ACE2-RBD) during 30 ns MD simulation.

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