Hordatines as a Potential Inhibitor of COVID-19 Main Protease and RNA Polymerase: An In-Silico Approach

Natural Products and Bioprospecting

Mohammed A. Dahab¹  Mostafa M. Hegazy²  Hatem S. Abbass³ 

[1] Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy, Al-Azhar University (Boys), 11884, Cairo, Egypt;Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University (Boys), 11884, Cairo, Egypt;Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University (Boys), 11884, Cairo, Egypt;Department of Pharmacognosy, Faculty of Pharmacy, Sinai University, 41636, Kantara, Egypt;

关键词: Barley;    COVID-19;    Docking;    Hordatine;    Protease;    RNA polymerase;    MOE;   

DOI  :  10.1007/s13659-020-00275-9

来源: Springer

【 摘 要 】

Total 40 natural compounds were selected to perform the molecular docking studies to screen and identify the potent antiviral agents specifically for Severe Acute Respiratory Syndrome Coronavirus 2 that causes coronavirus disease 2019 (COVID-19). The key targets of COVID-19, protease (PDB ID: 7BQY) and RNA polymerase (PDB ID: 7bV2) were used to dock our target compounds by Molecular Operating Environment (MOE) version 2014.09. We used 3 different conformations of protease target (6M0K, 6Y2F and 7BQY) and two different score functions to strengthen the probability of inhibitors discovery. After an extensive screening analysis, 20 compounds exhibit good binding affinities to one or both COVID-19 targets. 7 out of 20 compounds were predicted to overcome the activity of both targets. The top 7 hits are, flacourticin (3), sagerinic acid (16), hordatine A (23), hordatine B (24), N-feruloyl tyramine dimer (25), bisavenanthramides B-5 (29) and vulnibactins (40). According to our results, all these top hits was found to have a better binding scores than remdesivir, the native ligand in RNA polymerase target (PDB ID: 7bV2). Hordatines are phenolic compounds present in barley, were found to exhibit the highest binding affinity to both protease and polymerase through forming strong hydrogen bonds with the catalytic residues, as well as significant interactions with other receptor-binding residues. These results probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiment and accurate clinical trials are needed to confirm the preventive potentials of these compounds.Graphic Abstract

【 授权许可】

CC BY