Interactions mechanism of commonly used drugs for the treatment of Covid-19

Abstract

In this study conformation analysis of seven drugs commonly used in the treatment of COVID-19 was performed. The most stable conformers of the drug molecules were used as initial data for docking analysis. Using the Cavityplus program, the probable most active binding sites of both apo and holo forms of COVID-19 main protease enzyme (Mpro) and spike glycoprotein of SARSCoV-2 receptors were determined. The interaction mechanisms of the 7 FDA approved drugs (arbidol, colchicine, dexamethasone, favipiravir, galidesivir, hydroxychloroquine, remdesivir) were examined using the AutoDock Vina program. The six of the seven drugs were found to be more stable in binding to apo form of COVID-19 Mpro and spike glycoprotein. Moreover, a set of molecular mechanics (MM) Poisson-Boltzmann (PB) surface area (SA) calculations on the investigated drugs-protein systems were performed and the estimated binding free energy of remdesivir and the apo form of Mpro system was found to be the best. The interaction results of FDA drugs with the apo form of COVID-19 Mpro and spike glycoprotein can play an important role for the treatment of COVID-19.
 
 KEY WORDS: COVID-19, Drugs, Molecular modelling, Conformational analysis, Molecular docking
 
 Bull. Chem. Soc. Ethiop. 2020, 34(3), 613-623.
 DOI: https://dx.doi.org/10.4314/bcse.v34i3.16

Synthesis, Crystal Structure, Hirshfeld Surface and Docking Studies of 2‐(methacryloyloxy)ethyl‐6‐amino‐5‐cyano‐2‐methyl‐4‐(thiophen‐2‐yl)‐4H‐pyran‐3‐carboxylate

“…It can be observed from the Figure 13 that the major H‐bonding interactions were obtained within the limit of 3.0 Å. This has been found to be good agreement with earlier studies on COVID‐19 Mpro docking analysis [45–50] . Also, it has been noted that the van der Waals forces play a significant role in the ligand‐protein interaction as shown from the 2D docked pose of protein‐ligand interactions ( ACMP −6LU7).…”

“…This has been found to be good agreement with earlier studies on COVID-19 Mpro docking analysis. [45][46][47][48][49][50] Also, it has been noted that the van der Waals forces play a significant role in the ligand-protein interaction as shown from the 2D docked pose of protein-ligand interactions (ACMPÀ 6LU7). This should be due to the presence of lone electrons on the hetero atoms.…”

DFT investigations and molecular docking as potent inhibitors of SARS-CoV-2 main protease of 4-phenylpyrimidine

“…The molecular docking study was examined to investigate its efficacy in ligand binding to the against known COVID-19 (M pro ) proteins. The COVID-19 M pro is a desirable drug target for antiviral drug design toward COVID-19 treatment because the M pro is essential for polyprotein processing and virus maturation [73] , [74] , [75] . We tried to dock the 4-PPy with the three important proteins isolated from the virus.…”