In silico analysis and identification of promising hits against 2019 novel coronavirus 3C-like main protease enzyme

Chatterjee, Shilpa; Maity, Arindam; Chowdhury, Suchana; Islam, Ataul; Muttinini, Ravi K.; Sen, Debanjan

doi:10.1080/07391102.2020.1787228

Cited by 34 publications

(28 citation statements)

References 49 publications

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“…However, these residues are present in the loop region of the protein, therefore, these values may disturb the binding interactions. The higher value of RMSF infers that the greater flexibility of the protein and vice versa (Chatterjee et al, 2020 ). Each protein-ligand system shows lower RMSF values than apo-protein.…”

Section: Resultsmentioning

confidence: 99%

“…The compactness of a protein was indicated by Rg value. Higher the Rg value indicates a distorted protein structure (Chatterjee et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…The structural coordinates were saved for every 2 pico-second intervals. After PBC (periodic boundary condition) correction and removing solvents, ions etc., from the 130 ns atomistic molecular dynamics trajectory various parameters like root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), number of hydrogen bonds occurred between protein and ligand (HB), were calculated (Chatterjee et al, 2020 ) using in-built functions of GROMACS 2018.1 software.…”

Section: Methodsmentioning

confidence: 99%

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Identification of potential inhibitors of SARS-CoV-2 main protease and spike receptor from 10 important spices through structure-based virtual screening and molecular dynamic study

Sen¹,

Debnath

et al. 2020

Journal of Biomolecular Structure and Dynamics

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The outbreak of novel coronavirus disease (COVID-19) caused by SARS-CoV-2 poses a serious threat to human health and world economic activity. There is no specific drug for the treatment of COVID-19 patients at this moment. Traditionally, people have been using spices like ginger, fenugreek and onion, etc. for the remedy of a common cold. This work identifies the potential inhibitors of the main protease (M pro) and spike (S) receptor of SARS-CoV-2 from 10 readily available spices. These two proteins, S and M pro , play an important role during the virus entry into the host cell, and replication and transcription processes of the virus, respectively. To identify potential molecules an in-house databank containing 1040 compounds was built-up from the selected spices. Structure-based virtual screening of this databank was performed with two important SARS-CoV-2 proteins using Glide. Top hits resulted from virtual screening (VS) were subjected to molecular docking using AutoDock 4.2 and AutoDock Vina to eliminate false positives. The top six hits against M pro and top five hits against spike receptor subjected to 130 ns molecular dynamic simulation using GROMACS. Finally, the compound 1-, 2-, 3and 5-M pro complexes, and compound 17-, 18-, 19-, 20and 21spike receptor complexes showed stability throughout the simulation time. The ADME values also supported the drug-like nature of the selected hits. These nine compounds are available in onion, garlic, ginger, peppermint, chili and fenugreek. All the spices are edible and might be used as home remedies against COVID-19 after proper biological evaluation.

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Section: Resultsmentioning

confidence: 99%

“…The compactness of a protein was indicated by Rg value. Higher the Rg value indicates a distorted protein structure (Chatterjee et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Identification of potential inhibitors of SARS-CoV-2 main protease and spike receptor from 10 important spices through structure-based virtual screening and molecular dynamic study

Sen¹,

Debnath

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…In another study, drugs such as simeprevir, ergotamine, bromocriptine and tadalafil are proposed by the researcher ( 35 ). There was a virtual screening report on peptides drugs such as nafarelin and icatibant for repurposing to COVD-19 ( 36 ). Similarly, the drugs leupeptin, hemisulphate, pepstatin A, nelfinavir, birinapant, lypression and octreotide have been reported by targeting M pro in virtual screening ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Targeting SARS-CoV-2 Main Protease: A Computational Drug Repurposing Study

Baby

Maity

Mehta

et al. 2021

Archives of Medical Research

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Background and Aims Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) induced Novel Coronavirus Disease (COVID-19) has currently become pandemic worldwide. Though drugs like remdesivir, favipiravir, and dexamethasone found beneficial for COVID-19 management, they have limitations clinically, and vaccine development takes a long time. The researchers have reported key proteins which could act as druggable targets. Among them, the major protease M pro is first published, plays a prominent role in viral replication and an attractive drug-target for drug discovery. Hence, to target M pro and inhibit it, we accomplished the virtual screening of US-FDA approved drugs using well-known drug repurposing approach by computer-aided tools. Methods The protein M pro , PDB-ID 6LU7 was imported to Maestro graphical user interphase of Schrödinger software. The US-FDA approved drug structures are imported from DrugBank and docked after preliminary protein and ligand preparation. The drugs are shortlisted based on the docking scores in the Standard Precision method (SP-docking) and then based on the type of molecular interactions they are studied for molecular dynamics simulations. Results The docking and molecular interactions studies, five drugs emerged as potential hits by forming hydrophilic, hydrophobic, electrostatic interactions. The drugs such as arbutin, terbutaline, barnidipine, tipiracil and aprepitant identified as potential hits. Among the drugs, tipiracil and aprepitant interacted with the M pro consistently, and they turned out to be most promising. Conclusions This study shows the possible exploration for drug repurposing using computer-aided docking tools and the potential roles of tipiracil and aprepitant, which can be explored further in the treatment of COVID-19.

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“…Recently, several X-ray crystal structures of SARS-CoV-2 M pro in complex with covalent inhibitors were determined showing high structural similarity to that of SARS-CoV M pro , as expected from the 96% sequence identity (Jin et al, 2020 ; L. Zhang et al, 2020 ). These crystal structures have been recently used in several computational drug repurposing studies (Ancy et al, 2020 ; Aouidate et al, 2020 ; Arun et al, 2020 ; Chatterjee et al, 2020 ; Elmezayen et al, 2020 ; Khan et al, 2020 ; Kumar et al, 2020 ; J. Wang, 2020 ). Additional X-ray structure of SARS-CoV-2 M pro in complex with reversible dipeptide inhibitor X77 has been recently published (Mesecar, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

A multi-stage virtual screening of FDA-approved drugs reveals potential inhibitors of SARS-CoV-2 main protease

Mandour

Zlotos

Salem

2020

Journal of Biomolecular Structure and Dynamics

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Repurposing of approved pharmaceutical drugs for COVID-19 treatment represents an attractive approach to quickly identify promising drug candidates. SARS-CoV-2 main protease (M pro ) is responsible for the maturation of viral functional proteins making it a key antiviral target. Based on the recently revealed crystal structures of SARS-CoV-2 M pro , we herein describe a multi-stage virtual screening protocol including pharmacophore screening, molecular docking and protein-ligand interaction fingerprints (PLIF) post-docking filtration for efficient enrichment of potent SARS-CoV-2 M pro inhibitors. Potential hits, along with a cocrystallized control were further studied via molecular dynamics. A 150-ns production trajectory was followed by RMSD, free energy calculation, and H-bond analysis for each compound. The applied virtual screening protocol led to identification of five FDA-approved drugs with promising binding modes to key subsites of the substrate-binding pocket of SARS-CoV-2 M pro . The identified compounds belong to different pharmaceutical classes, including several protease inhibitors, antineoplastic agents and a natural flavonoid. The drug candidates discovered in this study present a potential extension of the recently reported SARS-CoV-2 M pro inhibitors that have been identified using other virtual screening protocols and may be repurposed for COVID-19 treatment.

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In silico analysis and identification of promising hits against 2019 novel coronavirus 3C-like main protease enzyme

Cited by 34 publications

References 49 publications

Identification of potential inhibitors of SARS-CoV-2 main protease and spike receptor from 10 important spices through structure-based virtual screening and molecular dynamic study

Identification of potential inhibitors of SARS-CoV-2 main protease and spike receptor from 10 important spices through structure-based virtual screening and molecular dynamic study

Targeting SARS-CoV-2 Main Protease: A Computational Drug Repurposing Study

A multi-stage virtual screening of FDA-approved drugs reveals potential inhibitors of SARS-CoV-2 main protease

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