Structure-Based Virtual Screening and Molecular Dynamics of Phytochemicals Derived from Saudi Medicinal Plants to Identify Potential COVID-19 Therapeutics

Abstract

Coronavirus disease 2019 (COVID-19) has affected almost every country in the world by causing a global pandemic with a high mortality rate. Lack of an effective vaccine and/or antiviral drugs against SARS-CoV-2, the causative agent, has severely hampered the response to this novel coronavirus. Natural products have long been used in traditional medicines to treat various diseases, and purified phytochemicals from medicinal plants provide a valuable scaffold for the discovery of new drug leads. In the present study, we performed a computational screening of an in-house database composed of ~1000 phytochemicals derived from traditional Saudi medicinal plants with recognised antiviral activity. Structure-based virtual screening was carried out against three druggable SARS-CoV-2 targets, viral RNAdependent RNA polymerase (RdRp), 3-chymotrypsin-like cysteine protease (3CLpro) and papain like protease (PLpro) to identify putative inhibitors that could facilitate the development of potential anti-COVID-19 drug candidates. Computational analyses identified three compounds inhibiting each target, with binding affinity scores ranging from-9.9 to -6.5 kcal/mol. Among these, luteolin 7-rutinoside, chrysophanol 8-(6-galloylglucoside) and kaempferol 7-(6’’-galloylglucoside) bound efficiently to RdRp, while chrysophanol 8-(6galloylglucoside), 3,4,5-tri-O-galloylquinic acid and mulberrofuran G interacted strongly with 3CLpro, and withanolide A, isocodonocarpine and calonysterone bound tightly to PLpro. These potential drug candidates will be subjected to further in vitro and in vivo studies and may assist the development of effective anti-COVID-19 drugs.

In Search of Herbal Anti-SARS-Cov2 Compounds

“…Quercetin showed inhibitory activity against SARS-CoV PL pro , although Papyriflavonol A was the most effective inhibitor of PL pro among those studied by Park et al (2017). Virtual structurebased screening revealed that withanolide A, isocodonocarpine, and calonysterone bind to PL pro (Alamri et al, 2020).…”

Mulberrofuran G, a Potent Inhibitor of SPIKE Protein of SARS Corona Virus 2

“…These amino acids interact with human ACE 2, too; it means these amino acids are proper residues for binding to any compound and inhibition of SPIKE of virus following that. This compound has properly binding energy for SPIKE of the virus compared to the same molecules, including some FDA-approved drugs or same designed and modified molecules, which was mentioned earlier; also there is a report of mulberrofuran G appropriate affinity to binding to 3cl-protease of SARS corona virus 2 (11); according to these reports, mulberrofuran G can be a potent candidate for the treatment of COVID-19. However, it needs more tests, such as in vitro and in vivo and clinical trials, to confirm its efficacy.…”