The Computational Preventive Potential of the Rare Flavonoid, Patuletin, Isolated from Tagetes patula, against SARS-CoV-2

Ahmed M Metwaly; Eslam B Elkaeed; Bshra A Alsfouk; Abdulrahman M Saleh; Ahmad E Mostafa; Ibrahim H Eissa

doi:10.3390/plants11141886

The Computational Preventive Potential of the Rare Flavonoid, Patuletin, Isolated from Tagetes patula, against SARS-CoV-2

Plants (Basel). 2022 Jul 20;11(14):1886. doi: 10.3390/plants11141886.

Authors

Ahmed M Metwaly^{1

2}, Eslam B Elkaeed³, Bshra A Alsfouk⁴, Abdulrahman M Saleh⁵, Ahmad E Mostafa¹, Ibrahim H Eissa⁵

Affiliations

¹ Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
² Biopharmaceutical Products Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, Egypt.
³ Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh 13713, Saudi Arabia.
⁴ Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
⁵ Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.

Abstract

The rare flavonoid, patuletin, was isolated from the flowers of Tagetes patula growing in Egypt. The rarity of the isolated compound inspired us to scrutinize its preventive effect against COVID-19 utilizing a multi-step computational approach. Firstly, a structural similarity study was carried out against nine ligands of nine SARS-CoV-2 proteins. The results showed a large structural similarity between patuletin and F86, the ligand of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Then, a 3D-Flexible alignment study of patuletin and F86 verified the proposed similarity. To determine the binding opportunity, patuletin was docked against the RdRp showing a correct binding inside its active pocket with an energy of -20 kcal/mol that was comparable to that of F86 (-23 kcal/mol). Following, several MD simulations as well as MM-PBSA studies authenticated the accurate binding of patuletin in the RdRp via the correct dynamic and energetic behaviors over 100 ns. Additionally, in silico ADMET studies showed the general safety and drug-likeness of patuletin.

Keywords: 3D-Flexible alignment; ADMET; MD simulations; SARS-CoV-2 RNA-dependent RNA polymerase; Tagetes patula; molecular docking; molecular similarity; patuletin; toxicity.

Grants and funding

PNURSP2022R142/Princess Nourah bint Abdulrahman University