Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS‑CoV‑2 through computational drug repurposing
Özet
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been signifcantly 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 classifed as “variant of concern” due to their increased transmissibility and better viral ftness.
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 signifcant 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
confrmed using MD simulations. The lead compounds were further evaluated for their potential use and side efects 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
