Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase

Abstract

Following the recent emergence of SARS-CoV-2 or coronavirus disease 2019 (COVID-19), drug discovery and vaccine design to combat this fatal infection are critical. In this study, an essential enzyme in the SARS-CoV-2 replication machinery, RNA-dependent RNA polymerase (RDRP), is targeted in a virtual screening assay using a set of 1,664 FDA-approved drugs, including sets of botanical and synthetic derivatives. A set of 22 drugs showed a high docking score of >−7. Notably, approximately one-third of the top hits were either from natural products or biological molecules. The FDA-approved phytochemicals were sennosides, digoxin, asiaticoside, glycyrrhizin, neohesperidin, taxifolin, quercetin and aloin. These approved natural products and phytochemicals are used as general tonics, antioxidants, cell protectives, and immune stimulants (nadid, thymopentin, asiaticoside, glycyrrhizin) and in other miscellaneous systemic or topical applications. A comprehensive analysis was conducted on standard precision and extra precision docking, two-step molecular dynamics simulations, binding energy calculations and a post dynamics analysis. The results reveal that two drugs, docetaxel and neohesperidin, showed strong binding profiles with SARS CoV-2 RdRP. These results can be used as a primer for further drug discovery studies in the treatment of COVID-19. This initiative repurposes safe FDA-approved drugs against COVID-19 RdRP, providing a rapid channel for the discovery and application of new anti-CoV therapeutics.

The impact of curcumin derived polyphenols on the structure and flexibility COVID-19 main protease binding pocket: a molecular dynamics simulation study

“…Pro168, His41, and Val116 residues contact probabilities between demethoxycurcumin-Mpro and bisdemethoxycurcumin-Mpro decreased (Table 3). Previous studies have shown COVID-19 main protease possesses a dynamic binding pocket loop comprising domain-I (residues 10-99) and domain-II (residues 100-184), in which most of the residues in this study laid (Jin et al, 2020;Kouznetsova et al, 2020;Kandeel, Kitade & Almubarak, 2020).…”

Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19

“…Several studies have demonstrated the efficacy of phytochemicals, such as flavonoids, anisotine, and other natural molecules, for the treatment of COVID-19 infection [ [18] , [19] , [20] , [21] , [22] ]. A recent study reports the RdRp inhibitory potential of FDA-approved phytochemicals that can be used to treat COVID-19 [ 23 ]. In the present study, we aimed to screen plant-based natural molecules (approximately 1064) for their inhibitory effects against RdRp and Mpro using an in silico molecular docking approach.…”

Use of Antioxidants for the Neuro-Therapeutic Management of COVID-19

“…Theaflavins, neohesperidin, naringenin, echinacoside, and salvianolic acid inhibited RNA-dependent RNA polymerase activity, blocking the active site of the groove (an active site for the polymerization of RNA but distal from the active site) through hydrophobic and hydrogen interactions [ 223 , 224 ]. Epigallocatechin gallate, theaflavin, and rutin digallate also show interactions with SARS-CoV-2 3CLpro, SARS-CoV-2 spike protein, and ACE2 receptor through a combination of hydrogen bonding, van der Waals and other hydrophobic interactions [ 225 , 226 ].…”

“…Other proposed candidates as neuroprotectors in patients with COVID-19 for their antioxidant capacity are: salicyl-carnosine [ 288 ], molecular hydrogen [ 224 ], cannabinoid type-2 receptor-selective agonists [ 289 ], propolis [ 290 ], thymoquinone, nigellidine, and α-hederin [ 291 ], agomelatine [ 292 ], and ozone [ 293 ].…”