ABSTRACT
The novel Coronavirus (COVID-19) has spread rapidly across the globe and has involved more than 215 countries and territories. Due to a lack of effective therapy or vaccine, urgent and concerted efforts are needed to identify therapeutic targets and medications. COVID-19 main protease represents a major target for drug treatment to inhibit viral function. The present study sought to evaluate medicinal plant compounds as potential inhibitors of the COVID-19 main protease using molecular docking and molecular dynamic analysis. The PDB files of COVID-19 main protease and some medicinal plant compounds were retrieved from the Protein Data Bank (http://www.rcsb.org) and Pubchem server, respectively. The Gromacs software was used for simulation studies, and molecular docking analysis was done using Autodock 4.2. The COVID-19 main protease simulation, compared with some phytochemicals docked to the COVID-19 main protease, were analyzed. Glabridin, catechin, and fisetin had the greatest tendency to interact with the COVID-19 main protease by hydrogen and hydrophobic interactions. Docking of these phytochemicals to COVID-19 main protease led to an increase in the radius of gyration (Rg), decrease in the Root mean square fluctuation (RMSF), and induced variation in COVID-19 main protease secondary structure. The high tendency interaction of glabridin, catechin, and fisetin to COVID-19 main protease induced conformational changes on this enzyme. These interactions can lead to enzyme inhibition. This simulated study indicates that these phytochemicals may be considered as potent inhibitors of the viral protease; however, more investigations are required to explore their potential medicinal use.Communicated by Ramaswamy H. Sarma.
Subject(s)
COVID-19 Drug Treatment , Catechin , Plants, Medicinal , Binding Sites , Hydrogen , Isoflavones , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptide Hydrolases , Phenols , Phytochemicals/chemistry , Phytochemicals/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Viral ProteasesABSTRACT
BACKGROUND: The COVID-19 is a pandemic viral infection with a high morbidity rate, leading to many worldwide deaths since the end of 2019. The RBD (Receptor Binding Domain) of SARS-CoV-2 through its spike utilizes several host molecules to enter host cells. One of the most important ones is the angiotensin-converting enzyme 2 (ACE2), an enzyme normally engaged in renin angiotensin pathway and is responsible for hypertension regulation. As different articles have analyzed separate compounds which can bind ACE2 as the potential virus entry blockers, and each one with a different molecular docking algorithm, in this study we compared all candidate compounds individually as well as their combinations using a unique validated software to introduce most promising ones. METHODS: We collected and prepared a list of all available compounds which potentially can inhibit RBD binding site of the ACE2 from different studies and then reanalyzed and compared them using the Patchdock (ver. 1.3) as a suitable molecular docking algorithm for analysis of separate compounds or their combinations. RESULTS: Saikosaponin A (e.g. in Bupleurum chinense), Baicalin (e.g. in several species in the genus Scutellaria), Glycyrrhizin (Glycyrrhiza glabra), MLN-4760 and Umifenovir better occupied ACE2 to inhibit viral RBD binding and are suggested as the top five inhibitors of the SARS-CoV-2 binding site of ACE2. Their combinatory effects were also inspiring concurrent ACE2 blockade. CONCLUSION: The results propose greatest compounds and their combinatory anti-SARS-CoV-2 effects in order to decrease the time and expenses required for further experimental designs.
