Isolation and In Silico Inhibitory Potential against SARS-CoV-2 RNA Polymerase of the Rare Kaempferol 3- O-(6″- O-acetyl)-Glucoside from Calligonum tetrapterum

Yerlan M Suleimen; Rani A Jose; Gulnur K Mamytbekova; Raigul N Suleimen; Margarita Y Ishmuratova; Wim Dehaen; Bshra A Alsfouk; Eslam B Elkaeed; Ibrahim H Eissa; Ahmed M Metwaly

doi:10.3390/plants11152072

Isolation and In Silico Inhibitory Potential against SARS-CoV-2 RNA Polymerase of the Rare Kaempferol 3- O-(6″- O-acetyl)-Glucoside from Calligonum tetrapterum

Plants (Basel). 2022 Aug 8;11(15):2072. doi: 10.3390/plants11152072.

Authors

Yerlan M Suleimen^{1

2}, Rani A Jose^{3

4}, Gulnur K Mamytbekova⁵, Raigul N Suleimen⁵, Margarita Y Ishmuratova⁶, Wim Dehaen³, Bshra A Alsfouk⁷, Eslam B Elkaeed⁸, Ibrahim H Eissa⁹, Ahmed M Metwaly^{10

11}

Affiliations

¹ Technopark Department, Kazakh University of Technology and Business, Nur-Sultan 010000, Kazakhstan.
² The Laboratory of Engineering Profile of NMR Spectroscopy, Sh. Ualikhanov Kokshetau University, Kokshetau 020000, Kazakhstan.
³ Molecular Design & Synthesis KU Leuven, Department of Chemistry, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
⁴ Department of Chemistry, St. Dominic's College, Mahatma Gandhi University, Kanjirappally 686512, India.
⁵ Department of Technical Physics, Faculty of Physics and Technology, L.N. Gumilyov Eurasian National University, Nur-Sultan 010010, Kazakhstan.
⁶ Department of Botany, E.A. Buketov Karaganda University, Karaganda 100024, Kazakhstan.
⁷ Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
⁸ Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh 13713, Saudi Arabia.
⁹ Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
¹⁰ Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
¹¹ Biopharmaceutical Product Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, Egypt.

Abstract

The phytochemical constituents of Calligonum tetrapterum Jaub. & Spach (Family Polygonaceae) were studied for the first time. The study resulted in the isolation of the rare flavonol glycoside, kaempferol 3-O-(6″-O-acetyl)-glucoside,(K3G-A). The potential inhibitive activity of K3G-A toward SARS-CoV-2 was investigated utilizing several in silico approaches. First, molecular fingerprints and structural similarity experiments were carried out for K3G-A against nine co-crystallized ligands of nine proteins of SARS-CoV-2 to reveal if there is a structural similarity with any of them. The conducted studies showed the high similarity of K3G-A and remdesivir, the co-crystallized ligand of SARS-CoV-2 RNA-dependent RNA polymerase (PDB ID: 7BV2), RdRp. To validate these findings, a DFT study was conducted and confirmed the proposed similarity on the electronic and orbital levels. The binding of K3G-A against RdRp was confirmed through molecular docking studies exhibiting a binding energy of -27.43 kcal/mol, which was higher than that of remdesivir. Moreover, the RdRp-K3G-A complex was subjected to several MD studies at 100 ns that authenticated the accurate mode of binding and the correct dynamic behavior. Finally, in silico ADMET and toxicity evaluation of K3G-A was conducted and denoted the safety and the drug-likeness of K3G-A. In addition to K3G-A, two other metabolites were isolated and identified to be kaempferol (K) and β-sitosterol (β-S).

Keywords: ADMET; Calligonum tetrapterum; DFT; MD simulations; SARS-CoV-2 RNA-dependent RNA polymerase; molecular docking; structural similarity.

Grants and funding

PNURSP2022R142/Princess Nourah bint Abdulrahman University