scholarly journals Drug Repurposing Approach against Novel Coronavirus Disease (COVID-19) through Virtual Screening Targeting SARS-CoV-2 Main Protease

Biology ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Kamrul Hasan Chowdhury ◽  
Md. Riad Chowdhury ◽  
Shafi Mahmud ◽  
Abu Montakim Tareq ◽  
Nujhat Binte Hanif ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Virtual Screening ◽  
Hydrophobic Interactions ◽  
Binding Free Energy ◽  
Specific Treatment ◽  
Dynamics Simulation ◽  
Experimental Drugs ◽  
Main Protease ◽  
Novel Coronavirus

Novel coronavirus disease (COVID-19) was identified from China in December 2019 and spread rapidly through human-to-human transmission, affecting so many people worldwide. Until now, there has been no specific treatment against the disease and repurposing of the drug. Our investigation aimed to screen potential inhibitors against coronavirus for the repurposing of drugs. Our study analyzed sequence comparison among SARS-CoV, SARS-CoV-2, and MERS-CoV to determine the identity matrix using discovery studio. SARS-CoV-2 Mpro was targeted to generate an E-pharmacophore hypothesis to screen drugs from the DrugBank database having similar features. Promising drugs were used for docking-based virtual screening at several precisions. Best hits from virtual screening were subjected to MM/GBSA analysis to evaluate binding free energy, followed by the analysis of binding interactions. Furthermore, the molecular dynamics simulation approaches were carried out to assess the docked complex’s conformational stability. A total of 33 drug classes were found from virtual screening based on their docking scores. Among them, seven potential drugs with several anticancer, antibiotic, and immunometabolic categories were screened and showed promising MM/GBSA scores. During interaction analysis, these drugs exhibited different types of hydrogen and hydrophobic interactions with amino acid residue. Besides, 17 experimental drugs selected from virtual screening might be crucial for drug discovery against COVID-19. The RMSD, RMSF, SASA, Rg, and MM/PBSA descriptors from molecular dynamics simulation confirmed the complex’s firm nature. Seven promising drugs for repurposing against SARS-CoV-2 main protease (Mpro), namely sapanisertib, ornidazole, napabucasin, lenalidomide, daniquidone, indoximod, and salicylamide, could be vital for the treatment of COVID-19. However, extensive in vivo and in vitro studies are required to evaluate the mentioned drug’s activity.

scholarly journals Identification of Novel Inhibitors of Type-I Mycobacterium Tuberculosis Fatty Acid Synthase Using Docking-Based Virtual Screening and Molecular Dynamics Simulation

2021 ◽  
Vol 11 (15) ◽  
pp. 6977
Author(s):  
Nidhi Singh ◽  
Shi-Qing Mao ◽  
Wenjin Li
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Mycobacterium Tuberculosis ◽  
Fatty Acid ◽  
Molecular Dynamics Simulation ◽  
Virtual Screening ◽  
Fatty Acid Synthase ◽  
Binding Free Energy ◽  
Dynamics Simulation ◽  
Type I

Mycobacterial fatty acid synthase type-I (FAS-I) has an important role in the de novo synthesis of fatty acids, which constitute a major component of the cell wall. The essentiality of FAS-I in the survival and growth of mycobacterium makes it an attractive drug target. However, targeted inhibitors against Mycobacterial FAS-I have not been reported yet. Recently, the structure of FAS-I from Mycobacterium tuberculosis was solved. Therefore, in a quest to find potential inhibitors against FAS-I, molecular docking-based virtual screening and molecular dynamics simulation were done. Subsequently, molecular dynamic simulations based on binding free energy calculations were done to gain insight into the predicted binding mode of putative hits. The detailed analysis resulted in the selection of four putative inhibitors. For compounds BTB14738, RH00608, SPB02705, and CD01000, binding free energy was calculated as −72.27 ± 12.63, −68.06 ± 11.80, −63.57 ± 12.22, and −51.28 ± 13.74 KJ/mol, respectively. These compounds are proposed to be promising pioneer hits.

Identification of novel selective MMP-9 inhibitors as potential anti-metastatic lead using structure-based hierarchical virtual screening and molecular dynamics simulation

2016 ◽  
Vol 12 (8) ◽  
pp. 2519-2531 ◽  
Author(s):  
Sukesh Kalva ◽  
Nikhil Agrawal ◽  
Adam A. Skelton ◽  
Lilly M. Saleena
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulation ◽  
Virtual Screening ◽  
Binding Free Energy ◽  
Pharmacophore Modeling ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Cross Docking

In this study, a novel MMP-9 inhibitor was identified using structure-based pharmacophore modeling, cross docking, binding free energy and molecular dynamics simulation studies.

scholarly journals Structure-based virtual screening suggests inhibitors of 3-Chymotrypsin-Like Protease of SARS-CoV-2 from Vernonia amygdalina and Occinum gratissimum

2021 ◽  
Author(s):  
Gideon A. Gyebi ◽  
Abdo A. Elfiky ◽  
Oludare M. Ogunyemi ◽  
Ibrahim M. Ibrahim ◽  
Adegbenro P. Adegunloye ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
In Silico ◽  
Hydrophobic Interactions ◽  
Binding Free Energy ◽  
Intermediate Formation ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Energy Calculation ◽  
Vernonia Amygdalina

Abstract An in-house library of 173 phytocompound structures from Vernonia amygdalina and Occinum gratissimum was screened against the active region of 3-Chymotrypsin-Like Protease (3CLpro) of SARS-CoV-2 in silico. Based on docking scores and reference inhibitors, a hit- list of 21 phytocompounds, with binding energies ranging from − 7.2 to -8.0 kcal/mol, was initially generated. Further docking against the 3CLpro of related coronaviruses (SARS-CoV and MERS-CoV), docking to 5 different representative conformations generated from the cluster analysis of SARS-CoV-2 3CLpro molecular dynamics simulation (MDS) trajectories, and in silico drug-likeness analyses, revealed two drug-like terpenoid structures as promising non-covalent inhibitors of SARS-CoV-2 3CLPro viz: neoandrographolide and vernolide. These terpenoid structures are accommodated within the substrate-binding pocket, and interacted with the catalytic dyad, the oxyanion loop (residues 138–145), and the S1/S2 subsites of the enzyme active site. With the aid of an array of hydrogen bonds and hydrophobic interactions with residues 142–145, these phytocompounds may stabilize the conformation of the flexible oxyanion loop; and thereby interfere with the tetrahedral oxyanion intermediate formation during proteolytic cleavage. Molecular dynamics simulation and binding free energy calculation further revealed that the terpenoid-enzyme complexes exhibit strong interactions and structural stability, which could be adapted for experimental models.

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