6-shogaol for COVID-19

Abstract Coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Although many vaccines have been developed against the virus, problems associated with vaccine resistance, vaccine apathy and the evolution of variants of the virus with increased transmissibility calls for the development of more effective and affordable drugs to combat the disease. Natural source drugs are regarded as an essential part of the therapy regimen for COVID-19 treatment and other viral respiratory infections as such needs to be exploited for the treatment of the virus globally. The study aimed to computationally screen the phytochemicals of some Nigerian plants used in the therapy of common cold for anti-COVID-19 activity. Phytochemical analysis of the plant extracts was performed employing standard techniques, while Gas chromatography–mass spectrometry was used to detect the bioactive compounds present in the extracts. The selected plant bioactive compounds were docked against the SARS-CoV-2 Main protease (Mpro), RNA-dependent RNA polymerase (RdRp), and S protein-ACE2 targets, while Lopinavir, Remdesivir and Favipiravir were included as standard ligands. The phytochemical constituents of the extracts were steroids, flavonoids, saponins, tannins, phenols, glycosides, terpenoids, and alkaloids. All the bioactive compounds exhibited acceptable drug-likeness and good oral bioavailability prediction, in addition to 89% of the compounds having slightly or practically non-oral toxicity using SwissADME and ProTox-II prediction servers. The overall result suggested that 3-Epimoretenol, Beta-Amyrin acetate, Methyl 3-oxours-12-en-23-oate, 20(29)-Lupenol acetate and Lanosterol acetate are the top most promising therapeutic bioactive natural compounds with antiviral activity against the SARS-CoV-2 Mpro, RdRp and spike protein when compared to standard drugs. Taken together, data obtained reveal that these bioactive natural compounds may have a very good potential as anti-COVID-19 therapy.

Since the outbreak of the COVID-19 (coronavirus disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants using a molecular docking approach to inhibit the main protease (Mpro) and spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina (AV) as a docking engine. A rule of five (Ro5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was performed by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs’ free energy of binding/ <math xmlns="http://www.w3.org/1998/Math/MathML" id="M1"> <mi mathvariant="normal">Δ</mi> <mi>G</mi> </math> ). As a comparison, nelfinavir (an antiretroviral drug), chloroquine, and hydroxychloroquine sulfate (antimalarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. This finding implied that several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate, which so far are recommended in the treatment of COVID-19. From quantum chemical DFT calculations, the ascending order of chemical reactivity of selected compounds was pectolinarin &gt; hesperidin &gt; rhoifolin &gt; morin &gt; epigallocatechin gallate. All isolated compounds’ C=O regions are preferable for an electrophilic attack, and O-H regions are suitable for a nucleophilic attack. Furthermore, Homo-Lumo and global descriptor values indicated a satisfactory remarkable profile for the selected compounds. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development of drugs to treat infections caused by SARS-CoV-2. The present study identified plant-based compounds that can be further investigated in vitro and in vivo as lead compounds against SARS-CoV-2.