Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS-CoV-2 through computational drug repurposing - PubMed (original) (raw)

Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS-CoV-2 through computational drug repurposing

Ozkan Fidan et al. Mol Divers. 2023 Feb.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classified as "variant of concern" due to their increased transmissibility and better viral fitness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous variants of concern, the Omicron variant has 15 mutations on the receptor-binding domain of spike protein and the changes in the key amino acid residues of S protein can enhance the binding ability of the virus to hACE2, resulting in a significant increase in the infectivity of the Omicron variant. Therefore, there is still an urgent need for treatment and prevention of variants of concern, particularly for the Omicron variant. In this study, an in silico drug repurposing was conducted through the molecular docking of 2890 FDA-approved drugs against the mutant S protein of SARS-CoV-2 for Omicron variant. We discovered promising drug candidates for the inhibition of alarming Omicron variant such as quinestrol, adapalene, tamibarotene, and dihydrotachysterol. The stability of ligands complexed with the mutant S protein was confirmed using MD simulations. The lead compounds were further evaluated for their potential use and side effects based on the current literature. Particularly, adapalene, dihydrotachysterol, levocabastine and bexarotene came into prominence due to their non-interference with the normal physiological processes. Therefore, this study suggests that these approved drugs can be considered as drug candidates for further in vitro and in vivo studies to develop new treatment options for the Omicron variant of SARS-CoV-2.

Keywords: Adapalene; Drug repurposing; Omicron variant; SARS-CoV-2; Vitamin D.

© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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Figures

Fig. 1

Fig. 1

Framework for in silico repurposing of existing drugs against viral S protein of the Omicron variant to temper the pathogenicity of viral infection in humans

Fig. 2

Fig. 2

Binding interactions of mutated monomeric subunit of the viral S protein (a) and original non-mutant variant (b) with the reported inhibitor K22

Fig. 3

Fig. 3

RMSD of the mutated S protein and complexed adapalene recorded during the MD simulation of 100 ns

Fig. 4

Fig. 4

RMSF of the monomeric subunit of the mutated S protein of the Omicron variant (a) and complexed adapalene (b) recorded during the MD simulation for 100 ns

Fig. 5

Fig. 5

The detailed contacts observed between macromolecular complex during 100 ns MD simulation. Green-colored bars: hydrogen bonds, blue-colored bars: water bridges, purple-colored bars: hydrophobic interactions, and pink-colored bars: ionic interactions

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