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https://doi.org/10.2478/acph-2021-0040

Computer-aided approaches reveal trihydroxychroman and pyrazolone derivatives as potential inhibitors of SARS-CoV-2 virus main protease

NOOR ATATREH orcid id orcid.org/0000-0002-2788-0875 ; College of Pharmacy, Al Ain University, Abu Dhabi, UAE, P.O. Box 112612
SHAIMA HASAN orcid id orcid.org/0000-0002-9984-243X ; College of Pharmacy, Al Ain University, Abu Dhabi, UAE, P.O. Box 112612
BASSAM R. ALI orcid id orcid.org/0000-0003-1306-6618 ; Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
MOHAMMAD A. GHATTAS orcid id orcid.org/0000-0002-2240-8037 ; College of Pharmacy, Al Ain University, Abu Dhabi, UAE, P.O. Box 112612


Puni tekst: engleski pdf 1.209 Kb

str. 325-333

preuzimanja: 723

citiraj


Sažetak

COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study is to target the SARS-CoV-2 virus main protease (Mpro) via structure-based virtual screening. Consequently, > 580,000 ligands were processed via several filtration and docking steps, then the top 21 compounds were analysed extensively via MM-GBSA scoring and molecular dynamic simulations. Interestingly, the top compounds showed favorable binding energies and binding patterns to the protease enzyme, forming interactions with several key residues. Trihydroxychroman and pyrazolone derivatives, SN02 and SN18 ligands, exhibited very promising binding modes along with the best MM-GBSA scoring of –40.9 and –41.2 kcal mol–1, resp. Hence, MD simulations for the ligand-protein complexes of SN02 and SN18 affirmed the previously attained results of the potential inhibition activity of these two ligands. These potential inhibitors can be the starting point for further studies to pave way for the discovery of new antiviral drugs for SARS-CoV-2.

Ključne riječi

COVID-19; Mpro; SARS-COV-2; antiviral; virtual screening; docking

Hrčak ID:

246136

URI

https://hrcak.srce.hr/246136

Datum izdavanja:

30.9.2021.

Posjeta: 1.808 *