Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (M^pro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

Abstract

<jats:p>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 by 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 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 done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / &amp;Delta;G). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial 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. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. 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. 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 lead compounds to treat infections caused by SARS-CoV-2.</jats:p>

In-silico analysis of the inhibition of the SARS-CoV-2 main protease by some active compounds from selected African plants

“…Regrettably, there are no specific therapies approved by recognized international health agencies, such as the WHO and US Food and Drug Administration (FDA) for SARS-CoV-2. 17 , 18 , 19 Presently, several agents, such as chloroquine, 20 hydroxychloroquine, 21 remdesivir, 22 lopinavir/ritonavir, 23 azithromycin, 24 and tocilizumab 25 are undergoing clinical trials under compassionate use protocols based on promising inhibitory effects exhibited against SARS-CoV-2, and related distemper in some in vitro experiments is now a milestone for drug repurposing against this viral malady. Despite their success in clinical reports, none have gained approval for use against SAR-CoV-2 because their curative outcomes remain very limited and their toxic side-effects cannot be ignored.…”

The potential of leaf extract of Pangium edule Reinw as HIV-1 protease inhibitor: A computational biology approach

“…Plant D. stramonium was also reported to have an antiviral potential (Ivanov and Nikalov, 1988). Ethyl cholate and bis(3,5,5-trimethylhexyl) phthalate were reported to have potential antiviral activity against SARS-CoV-2 in an in silico study (Tallei et al, 2020).…”

“…The docking analysis used in this study followed the methodologies utilized in Tallei et al (2020). The three-dimensional (3D) structural information of the macromolecule HIV-1 protease (PDB ID: 3NU3) determined by X-ray crystallography was downloaded from the protein data bank (http://www.rcsb.org/pdb).…”

“…Medicinal plants are often used as sources of active compounds that have the potential to be developed as antimicrobial, antifungal, antibacterial, and antiviral (Calland et al, 2012;Estevam et al, 2015;Hu et al, 2013;Ningsih et al, 2019;Nuraskin et al, 2019Nuraskin et al, , 2020Pratiwi et al, 2015;Rahmad et al, 2019;Sardi et al, 2013;Tallei et al, 2019a;Tallei et al, 2019b). One of the medicinal plants in which the leaves are used as food for the people of North Sulawesi is Pangi (Pangium edule) (Calland et al, 2012;Hu et al, 2013;Rahmad et al, 2019).…”

Repositioning microbial biotechnology against COVID‐19: the case of microbial production of flavonoids

“…Several docking studies investigating the interaction of flavonoids with the SARS‐CoV‐2 spike protein are available (Maiti and Banerjee, 2020; Yu et al ., 2020; Tallei et al ., 2020; for further preprints see SI2). Several studies also investigated the interaction of flavonoids with the human ACE‐2 receptor (Joshi et al ., 2020; Bhowmik et al ., 2020; Maiti and Banerjee, 2020; SI2).…”