Abstract
The urgent need for effective treatments for COVID-19 has developed, encouraging pharmaceutical companies to develop or redirect substances against SARS-CoV-2. Among them, substances used against worms, malaria, or bacteria were targeted to combat the virus. Such substances have been used in clinical trials and evaluated in vitro and in silico regarding the action on viral proteins, pharmacodynamics and toxicity of drugs. In this study, we conducted a systematic review of peer-reviewed articles involving molecules of plant origin with potential antiviral action on SARS-CoV-2. Reports containing the combinations of key words herbal, medicinal plants, natural products, and SARS-CoV-2 available from 01-01-2019 to 28-08-2020 in the Pubmed Central and World Wide Science sites were selected. A total of 677 items were retrieved. Of these, 170 were excluded because they were not complete, peer reviewed, freely, or related to vegetable products. Of the remaining, 345 were review articles, 23 were discussions, 4 were clinical trials, 14 showed in vitro experiments, and 121 were in silico studies. The proteins of SARS-CoV-2 considered as the therapeutic targets for the molecular docking were the structural spike glycoprotein (S protein), membrane protein Mpro, papain- like protease (PLpro), and RNA-dependent RNA polymerase (RdRp). Also, some studies have addressed the cell receptor ACE2 and natural products interaction. From in silico tests, therefore, 149 isolated plant molecules were identified with binding affinity to SARS-CoV-2 Mpro. Also, pharmacokinetic properties and bioavailability of some products were investigated highlighting the products nimbolide, withaferin-A, caffeic acid derivatives, rhamnetin, delta d-Viniferin, myri-citrin, chrysanthemin, myritilin, taiwanhomoflavone A, lactucopicrin 15-oxalate, nympholide A, afzelin, biorobin, herperidin and phyllaemblicin B, glycyrrhizic acid, and rutin. As reported, rutin may influence viral functional protein assembly and host inflammatory suppression. Its affinity for Mpro and toll like receptors (TLRs) besides in vivo results render rutin a potential novel therapeutic anti-coronavirus strategy. This study highlights the in silico diversity of plant metabolites with high potential of antiviral activity against SARS-CoV-2 as alternatives in the repurposing course against COVID-19 as well as other viral pandemics that may arise.
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