Open Access

ARTICLE

Investigation of SARS-CoV-2 Main Protease Potential Inhibitory Activities of Some Natural Antiviral Compounds Via Molecular Docking and Dynamics Approaches

Nada M. Mostafa^1,5,#, Muhammad I. Ismail^2,#, Amr M. El-Araby³, Dina M. Bahgat¹, Ahmed M. Elissawy^1,5, Ahmed M. Mostafa⁴, Omayma A. Eldahshan^1,5,*, Abdel Nasser B. Singab^1,5,*

1 Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt
4 Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt
5 Center for Drug Discovery and Development Research, Ain Shams University, Cairo, 11566, Egypt

* Corresponding Authors: Omayma A. Eldahshan. Email: ; Abdel Nasser B. Singab. Email:
# These authors contributed equally to the work

Phyton-International Journal of Experimental Botany 2022, 91(5), 1089-1104. https://doi.org/10.32604/phyton.2022.018239

Received 09 July 2021; Accepted 08 October 2021; Issue published 24 January 2022

Abstract

Coronaviruses caused an outbreak pandemic disease characterized by a severe acute respiratory distress syndrome leading to the infection of more than 200 million patients and the death of more than 4 million individuals. The primary treatment is either supportive or symptomatic. Natural products have an important role in the development of various drugs. Thus, screening of natural compounds with reported antiviral activities can lead to the discovery of potential inhibitory entities against coronaviruses. In the current study, an in-silico molecular docking experiment was conducted on the effects of some of these natural antiviral phytoconstituents, (e.g., procyanidin B2, theaflavin, quercetin, ellagic acid, caffeoylquinic acid derivatives, berginin, eudesm-1β, 6α, 11-triol and arbutin), on the crystal structure of SARS-CoV-2 main protease (PDB ID: 6w63) using AutoDock-Vina software. Many of the docked compounds revealed good binding affinity, with procyanidin B2 (–8.6 Kcal/mol) and theaflavin (–8.5 Kcal/mol) showing a better or similar binding score as the ligand (–8.5 Kcal/mol). Molecular dynamics simulations were carried out at 100 ns and revealed that procyanidin B2 forms a more stable complex with SARS-CoV-2 main protease than theaflavin. Procyanidin B2, theaflavin, and 4,5-dicaffeoylquinic acid were evaluated for toxicity by ProTox-II webserver and were non-toxic according to the predicted LD50 values and safe on different organs and pathways. Additionally, these phytoconstituents showed good ADME properties and acceptable lipophilicity, as evaluated using WLOGP. Amongst the tested compounds, procyanidin B2 showed the highest lipophilic value. It is worth mentioning that these natural inhibitiors of SARS-CoV-2 main protease are components of green and black tea that can be used as a supporting supplement for COVID patients or as potential nuclei for further drug design and development campaigns.

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