Abstract
Historically, plants have been sought after as bio-factories for the production of diverse chemical compounds that offer a multitude of possibilities to cure diseases. To combat the current pandemic coronavirus disease 2019 (COVID-19), plant-based natural compounds are explored for their potential to inhibit the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The present study is aimed at the investigation of antiviral action of several groups of phytoconstituents against SARS-CoV-2 using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and spike (S) glycoprotein receptor binding domain (RBD) to ACE2 (PDB code: 6M0J) of SARS-CoV-2. For binding affinity evaluation, the docking scores were calculated using the Extra Precision (XP) protocol of the Glide docking module of Maestro. CovDock was also used to investigate covalent docking. The OPLS3e force field was used in simulations. The docking score was calculated by preferring the conformation of the ligand that has the lowest binding free energy (best pose). The results are indicative of better potential of solanine, acetoside, and rutin, as Mpro and spike glycoprotein RBD dual inhibitors. Acetoside and curcumin were found to inhibit Mpro covalently. Curcumin also possessed all the physicochemical and pharmacokinetic parameters in the range. Thus, phytochemicals like solanine, acetoside, rutin, and curcumin hold potential to be developed as treatment options against COVID-19.
Highlights
The World Health Organization (2020) declared coronavirus disease 2019 (COVID-19) as a pandemic, and it is affecting more than 210 countries and territories in the world
To achieve a multitarget approach and to find the potential candidate for treating COVID-19 infection, molecular docking studies were performed against two protein structures of SARSCov-2: (i) Main protease, main protease (Mpro) (PDB ID: 6LU7) and (ii) Spike glycoprotein (PDB ID: 6M0J) in GLIDE (Grid-based Ligand Docking with Energetics) of Schrödinger suite v 12.3 (Schrödinger, 2020)
From the above molecular docking studies against most promising targets of SARS-CoV2 virus [i.e., Mpro and Spike receptor-binding domain (RBD) bound to ACE2, we found that phytoconstituents like Acetoside (2), Rutin
Summary
The World Health Organization (2020) declared coronavirus disease 2019 (COVID-19) as a pandemic, and it is affecting more than 210 countries and territories in the world. As per the WHO report (August 16, 2020), there have been 21,294,845 confirmed cases of COVID-19 and over 761,779 total deaths occurred due to it (World Health Organization, 2020). The SARS-CoV-2 virus targets the host cells through the viral spike (S) protein, which binds to the ACE2 receptor of the host cells (Fung and Liu, 2014). After the S protein-ACE2 binding, the virus utilizes the host cell receptors (TMPRSS2) and enters into the cytosol of the host cell. Β-CoVs produce pp1a and pp1ab by translation of the genomic RNA. They are proteolytically cleaved into structural and non-structural proteins by main protease (Mpro) known as 3-chymotrypsin-like protease (3CLpro) and by papain-like protease (PLpro) (Fehr and Perlman, 2015). Once the virion assembly gets ready, it will be released from the host cell
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