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Abstract
Background: Accessing COVID-19 vaccines is a challenge despite successful clinical trials. This burdens the COVID-19 treatment gap, thereby requiring accelerated discovery of anti-SARS-CoV-2 agents. Thus, this study explored the potential of anti-HIV reverse transcriptase (RT) phytochemicals as inhibitors of SARS-CoV-2 non-structural proteins (nsps) by targeting in silico key sites in the structures of SARS-CoV-2 nsps. Moreover, structures of the anti-HIV compounds were considered for druggability and toxicity. 104 anti-HIV phytochemicals were subjected to molecular docking with papain-like protease (nsp3), 3-chymotrypsin-like protease (nsp5), RNA-dependent RNA polymerase (nsp12), helicase (nsp13), SAM-dependent 2’-O-methyltransferase (nsp16) and its cofactor (nsp10), and endoribonuclease (nsp15). Drug-likeness and ADME (absorption, distribution, metabolism, and excretion) properties of the top ten compounds per nsp were predicted using SwissADME. Their toxicity was also determined using OSIRIS Property Explorer.
Results: Among the twenty-seven top-scoring compounds, the polyphenolic natural products amentoflavone (1), robustaflavone (4), punicalin (9), volkensiflavone (11), rhusflavanone (13), morelloflavone (14), hinokiflavone (15), and michellamine B (19) were multi-targeting and had the strongest affinities to at least two of the nsps (Binding Energy = -7.7 to -10.8 kcal/mol). Friedelin (2), pomolic acid (5), ursolic acid (10), garcisaterpenes A (12), hinokiflavone (15), and digitoxigenin-3-O-glucoside (17) were computationally druggable. Moreover, compounds 5 and 17 showed good gastrointestinal absorptive property. Most of the compounds were also predicted to be non-toxic.
Conclusions: Twenty anti-HIV RT phytochemicals showed multi-targeting inhibitory potential against SARS-CoV-2 nsp3, 5, 10, 12, 13, 15, and 16, and can therefore be used as prototypes for anti-COVID-19 drug design.
