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>Background: Since the outbreak of the coronavirus disease 2019 (COVID-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 cause of COVID-19. The search for plant-based antivirals against the SARS-CoV-2 is promising, as several plants have been shown to possess antiviral activities against betacoronaviruses (beta-CoVs) Objective: The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and Spike (S) Glycoprotein (PDB code: 6VXX) of SARS-CoV-2. Methods: Evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. For each compound that was docked, a rule of five was calculated to determine whether a compound with certain pharmacological or biological activities might have chemical and physical properties that would make it an active drug orally in humans. Determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. Results: The results showed that hesperidine, cannabinoids, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and cannabinoids had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro/3CLpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Conclusion: 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.</jats:p>

In silico analysis of the interactions of certain flavonoids with the receptor-binding domain of 2019 novel coronavirus and cellular proteases and their pharmacokinetic properties

“…According to Maiti and Banerjee ( 2020 ), catechins, such as epigallocatechin gallate or theaflavin gallate, interact more strongly with the amino acids of the spike protein than hydroxychloroquine. There are also some data in the literature that some catechins, such as theaflavin digallate, epigallocatechin gallate and gallocatechin gallate, inhibit the main protease of 2019-nCoV together with the spike glycoprotein (Manish, 2020 ; Peterson, 2020 ; Sayed et al., 2020 ; Tallei et al., 2020 ). In addition to 2019-nCoV, molecular docking studies performed on (-) -epicatechin 3- O -(3′- O -methyl) gallate, a green tea polyphenol, showed that the molecule in question can inhibit TMPRSS, a cellular protease (Rahman et al., 2020 ).…”

In Search of Herbal Anti-SARS-Cov2 Compounds

“…Antiviral features of compounds can be determined by matching them as a ligand to known targets using molecular dynamics and docking simulations (Zhang et al, 2020a). Tallei et al (2020) made a list of natural components with M proinhibitor effect; among them are hesperidin, morine, rhoifolin, pectolinarin, and nabiximols. Binding interaction and ligand affinity of these compounds to M pro was the same as of nelfinavir, and even better than chloroquine and hydroxychloroquine sulfate, − recommended by the FDA as emergency anti-COVIDtreatment anti-malarial drugs (Tallei et al, 2020).…”

“…Tallei et al (2020) made a list of natural components with M proinhibitor effect; among them are hesperidin, morine, rhoifolin, pectolinarin, and nabiximols. Binding interaction and ligand affinity of these compounds to M pro was the same as of nelfinavir, and even better than chloroquine and hydroxychloroquine sulfate, − recommended by the FDA as emergency anti-COVIDtreatment anti-malarial drugs (Tallei et al, 2020). Quercetin-3-β-galactoside showed inhibitory activity against SARS-CoV M pro in silico, via docking simulation, and also in enzymatic inhibition assays.…”

Hydrodynamic Cavitation-based Rapid Expansion of Hesperidin-rich Products from Waste Citrus Peel as a Potential Tool Against COVID-19

“…In the second of the later studies, plant bioactive compounds were assessed based on their binding affinity with M pro /3CL pro and spike glycoprotein of SARS-CoV-2, by means of a molecular docking approach [39]. The well-known drugs, namely nelfinavir, chloroquine and hydroxychloroquine sulfate, which were widely recommended for clinical trials against COVID-19, were used as a comparison.…”

“…However, when it comes to bioavailability after oral administration, things get more complicated. Indeed hesperidin, with poor water solubility, showed also relatively poor bioavailability, which could negatively affect the performance of in vivo and clinical trials [39].…”