Natural compounds as potential inhibitors of novel coronavirus (COVID-19) main protease: An in silico study

Abstract

COVID-19 pandemic, a novel coronavirus disease is caused by severe acute respiratory syndrome corona virus, SARS-CoV-2. It was first reported in Wuhan, China and has now expanded to more than 190 countries across the world. Till date, there is no specific medication available to prevent or target SARS CoV-2 infection. Very recently, the crystal structure of COVID-19 main protease (M pro ) was revealed by Liu et al. (2020). SARS-CoV-2 main protease (M pro ) is a key enzyme that plays a crucial role in viral replication and transcription. Thus, M pro could be a promising target to inhibit SARS-CoV-2 infection. Natural compounds due to their structural diversity and safety are considered as an excellent source of antiviral drugs. In this study, we selected Herbacetin, Rhoifolin, Pectolinarin, Apigenin, Luteolin, Amentoflavone, Daidzein, Puerarin, Epigallocatechin, Gallocatechin gallate, Resveratrol, Maslinic acid, Piperine and Ganomycin B to target the SARS-CoV-2 main protease (M pro ) using in silico tools. These compounds were examined based on ADME, drug likeness, docking studies, MD simulations using CABS-flex 2.0, and prediction of major toxicity parameters (hepatotoxicity & cytotoxicity) to check the safety aspects of the selected compounds. We also investigated the similarity of these compounds, if any, with FDA approved drugs using Swiss similarity. The docking results were found in the order of Amentoflavone (-9.13 kcal/mol), Ritonavir (-8.52 kcal/mol), Lopinavir (-8.5 kcal/mol), Puerarin (-7.97 kcal/mol), Maslinic acid (-7.97 kcal/mol), Piperine (-7.65 kcal/mol), Gallocatechin gallate (-7.59 kcal/mol), Luteolin (-7.58 kcal/mol), Apigenin (-7.42 kcal/mol), Resveratrol (-7.41 kcal/mol), Herbacetin (-7.4 kcal/mol), Daidzein (-7.32 kcal/mol),Rhoifolin (-6.71 kcal/mol), Ganomycin B (-6.46 kcal/mol), Epigallocatechin (-6.13 kcal/mol), and Pectolinarin (-5.88 kcal/mol). Among these selected natural compounds, Amentoflavone and Puerarin were the two top leads which showed the lowest binding energies. Interestingly, Amentoflavone showed highest binding affinity among all the selected compounds. Our promising findings based on in-silico studies warrants further clinical trial in order to use these compounds as potential inhibitors of SARS-CoV-2 protease.

Screening of phytochemicals as potent inhibitor of 3-chymotrypsin and papain-like proteases of SARS-CoV2: an in silico approach to combat COVID-19

“…Similarly, Mishra et al. ( 2020 ) also revealed that amentoflavone made strongest interaction with the SARS-CoV2 main protease (–9.13 kcal/mol). In a 10 ns MD simulation they have reported that the peak RMSF was observed in amino acid residue-106, 181, 46 and 151 which is different from our findings.…”

Progress in Developing Inhibitors of SARS-CoV-2 3C-Like Protease

“…Molecular interactions between SARS-CoV-2 3CL pro and natural compounds were also analyzed through docking and molecular dynamics (MD) simulation. Amentoflavone and puerarin were considered to be potential protease inhibitors [ 102 ]. In addition, computer-aided method can be adopted to design inhibitors, and several small-molecule compounds have been designed [ 103 , 104 ].…”

Structural basis for the inhibition of SARS-CoV2 main protease by Indian medicinal plant-derived antiviral compounds

“…However, among them, amentoflavone from Torreyanucifera plant showed highest binding energy of −10.0 kcal/mol with the SARS-COV2 main protease and further In vitro and In Vivo studies are required to understand the underlying molecular mechanisms and signaling pathways involved in SARS-COV2 main protease inhibition. In the literature, there are reports based on insilico studies that the amentoflavone can act as a potential inhibitor of SARS-CoV2 (Mishra et al., 2020 ). Furthermore, we performed molecular dynamics simulations and free energy calculations on the top five compounds to validate our findings from the molecular docking procedure.…”