Potential of Natural Products as SARS-COV-2 RNA Dependent RNA Polymerase Inhibitors: A Molecular Docking Study

Abstract

COVID-19 is a transmissible respiratory disease caused by severe acute respiratory syndrome coronaviruses 2 (SARS CoV-2) which emerged in December 2019 in Wuhan, China. Several attempts have been done to examine the potential of natural compounds to prevent the multiplication of SARS-CoV-2 since the outbreak of the pandemic. The present study aimed to evaluate the potential of twenty selected natural products from published literature as SARS CoV-2 RNA-dependent RNA polymerase inhibitors using a molecular docking approach. Out of them, nine compounds were published previously for their promising antiviral drug-like activity by various investigators whereas the remaining eleven were new and isolated from different Ethiopian flora in the applied chemistry department of ASTU. To test if these compounds meet the criteria for use as active drugs in humans, a rule of five (Ro5) was calculated. Remdesivir, an FDA-approved emergency medication, was utilized as a control. The docking evaluation, physicochemical, pharmacokinetic properties, and toxicity profiles were computed using Autodoc vina 4.2, SwissADME, and Protox II webservers, respectively. Among the examined compounds, nicotflorin(59) violates Lipinski's rule of five out of twenty compounds and hence docking evaluation proceeded for the remaining 19 natural products. The docking results showed that biscriptolepin(60), berbamin(52), CPD63, Jatrorrhizine(55), Dicentrin(53), CPD61, and CPD66, CPD69, and CPD70, displayed better binding affinity with ΔG values of -9.0, -8.8, and -7.7, , -7.4, -7.1, -6.8 kcal/mol, respectively, compared to remdesivir (-6.7 kcal/mol) suggesting the potential of these compounds as SARS CoV-2 RNA dependent RNA polymerase inhibitors. The toxicological endpoints prediction study result showed the LD50 values ranged from 96-89470 mg/Kg. Acute toxicity predictions showed that the compounds under consideration are not fatal; rather, they can be classified as nontoxic to highly toxic classes, with dicentrin(53), coptisine (54), and palmatine(56) active for all predicted toxicological endpoint and psilocybin(58), biscryptolepine (60), CPD61, CPD62, CPD68, and CPD69 with no predicted toxicological endpoints. Overall, the results of the present study revealed that four of the studied compounds i.e. Biscryptolepine(60) and CPD61(C15H14O6) with zero toxicological endpoints, and CPD63 (C18H17NO2), and CPD70(C14H8N2O with one toxicological are promising compounds as SARS CoV-2 RNA dependent RNA polymerase inhibitors hence further experimental in vitro and in vivo therapeutic examination on COVID-19 is recommended.