Kolaviron (Kolaflavanone), apigenin, fisetin as potential Coronavirus inhibitors: In silico investigation

Abstract

The outbreak of COVID-19 caused by SARS-CoV-2 is increasing with an alarming rate of associated frightening mortality without no known approved therapy. The emergence of new infectious diseases and increase in frequency of drug resistant viruses demand effective and novel therapeutic agents. This study investigated the putative inhibitory potentials of apigenin, fisetin, kolaflavanone, and remdesivir towards SARS-COV2 major protease (6LU7) using in silico methods. Pharmacodynamics, pharmacokinetics and toxicological profiles of the compounds were also examined using the pkCSM server. All the compounds showed good affinity to the binding pocket of 6LU7. It was observed that kolaflavanone exhibited the highest binding affinity when compared to apigenin, fisetin, and remdesivir. The amino acids ASN238, TYR237, LEU286, and LEU287 were showed as the key residues for kolaflavanone binding to human SARS-COV2 major protease. The Pharmacodynamics and pharmacokinetics results suggested that all the tested compounds have significant drug likeness properties and they could be absorbed through the human intestine. Additionally, all the tested compounds except remdesivir are not hepatoxic and also displayed non or relatively low toxic effects in human. Summarily, the results of this study indicated that all the tested compounds are potential putative inhibitors of SARS-COV2 major protease with no or low toxicity effects. However, further experimental and clinical studies are needed to further explore their activities and validate their efficacies against COVID-19.

Identification of Potential Flavonoid Inhibitors of the SARS-CoV-2 Main Protease 6YNQ: A Molecular Docking Study

“…The flavonol fisetin also produced both hydrogen and pi alkyl bonds with the catalytic center of 6YNQ, although its binding energy was somewhat lower than rutin and baicalein. Other studies have reported binding of fisetin with 6LU7 [ 38 ] . Given these results, we propose that a combination of rutin, baicalein and fisetin may produce a synergistic inhibition of both catalytically active residues in 6YNQ, improving its overall inhibition.…”

Neurological Complications in COVID-19: Implications on International Health Security and Possible Interventions of Phytochemicals

“…Similarly, in silico study in our laboratory revealed that apigenin displayed a significant binding affinity with the SARS-CoV-2 major protease (6 LU7). The result also suggested that apigenin could be a potential inhibitor of SARS-COV-2 [53].…”

“…Thіѕ ѕhоwѕ thаtkоlаvіrоn соuld bе a prospective drug fоr the еffесtіvе management and/or trеаtmеnt of Parkinson's disease. Kolaviron has been noted to be a potential anti-COVID-19 drug candidate in a computational experimental study aimed to screen phytochemicals in drug repurposing approach to combat COVID-19 [53]. The study employed USCF Chimera in virtual screening and molecular docking for possible inhibitors of SARS-CoV-2.…”

A systematic review on COVID-19 pandemic with special emphasis on curative potentials of Nigeria based medicinal plants

“…The phytochemical screening of garlic has also been reported to have chemical compounds such as saponin, tannin, carbohydrates, cardio glycoside, alkaloids, flavonoid, phlobatannin and glycoside (Pavni et al, 2011). Apigenin and fisetin have also been documented as potential inhibitors of coronavirus-2 in an in silico investigation (Oladele et al, 2020e).…”