In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

Abstract

Severe acute respiratory syndrome has relapsed recently as novel coronavirus causing a life threat to the entire world in the absence of an effective therapy. To hamper the replication of the deadly SARS CoV-2 inside the host cells, systematic in silico virtual screening of total 267,324 ligands from Asinex EliteSynergy and BioDesign libraries has been performed using AutoDock Vina against RdRp. The molecular modeling studies revealed the identification of twenty-one macrocyclic hits ( 2 - 22 ) with better binding energy than remdesivir ( 1 ), marketed SARS CoV-2 inhibitor. Further, the analysis using rules for drug-likeness and their ADMET profile revealed the candidature of these hits due to superior oral bioavailability and druggability. Further, the MD simulation studies of top two hits ( 2 and 3 ) performed using GROMACS 2020.1 for 10 ns revealed their stability into the docked complexes. These results provide an important breakthrough in the design of macrocyclic hits as SARS CoV-2 RNA replicase inhibitor.

Machine learning prediction of 3CL SARS-CoV-2 docking scores

“…In an immediate action, scientists around the world boosted contra action in the effort to develop possible drugs and/or identify potential targets for drug refurbishment and repurposing [17] , [18] , [19] , [8] , [20] , [21] , [22] , [23] , [24] , [25] . Currently, vaccine development by pharmaceutical companies offers great action against virus spread and harm [26] , [27] , [28] .…”

Quantum mechanical studies of 5‐amino‐2‐(6‐(2‐hydroxyethyl)‐3‐oxononyl) cyclohex‐2‐enone isolated from a marine algae

“…The titled compound C1 predicts the biological property the ADME tools is most important one. [67] The ADME properties was done by Swiss ADME online tools. [68,69] Compound C1 physicochemical properties such as hydrogen bond donor, [70] hydrogen bond acceptor, number of heavy atoms, number of rotatable bonds etc., are tabulated in table S4.…”

A review on synthetic account of 1,2,4-oxadiazoles as anti-infective agents

“…Most of the parts of the world have been affected from deadly infectious disease including tuberculosis ( Mycobacterium tuberculosis , Mtb ) [ 1 , 2 ], malaria ( Plasmodium falciparum ) [ 3 ], Chagas disease or American trypanosomiasis ( Trypanosoma cruzi ) [ 4 ], nosocomial infections ( Staphylococcus aureus or methicillin-resistant S. aureus , MRSA) [ 5 ] and also the recent severe acute respiratory syndrome coronavirus-2 (SARS CoV-2, caused by Coronavirus) [ 6 – 8 ]. The scarcity of curative action of antibiotics and anti-infective agents and complex genomic structure of microorganism has led to resistance among them leading to ineffectiveness of the currently used treatment regimen [ 9 ].…”