scholarly journals Putative SARS-CoV-2 Mpro Inhibitors from an In-House Library of Natural and Nature-Inspired Products: A Virtual Screening and Molecular Docking Study

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3745 ◽  
Author(s):  
Stefania Mazzini ◽  
Loana Musso ◽  
Sabrina Dallavalle ◽  
Roberto Artali
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Chemical Space ◽  
Structural Diversity ◽  
Docking Study ◽  
Binding Pocket ◽  
Molecular Docking Study ◽  
Screening Experiments ◽  
Good Ability ◽  
Wide Range

A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has been the cause of a recent global pandemic. The highly contagious nature of this life-threatening virus makes it imperative to find therapies to counteract its diffusion. The main protease (Mpro) of SARS-CoV-2 is a promising drug target due to its indispensable role in viral replication inside the host. Using a combined two-steps approach of virtual screening and molecular docking techniques, we have screened an in-house collection of small molecules, mainly composed of natural and nature-inspired compounds. The molecules were selected with high structural diversity to cover a wide range of chemical space into the enzyme pockets. Virtual screening experiments were performed using the blind docking mode of the AutoDock Vina software. Virtual screening allowed the selection of structurally heterogeneous compounds capable of interacting effectively with the enzymatic site of SARS-CoV-2 Mpro. The compounds showing the best interaction with the protein were re-scored by molecular docking as implemented in AutoDock, while the stability of the complexes was tested by molecular dynamics. The most promising candidates revealed a good ability to fit into the protein binding pocket and to reach the catalytic dyad. There is a high probability that at least one of the selected scaffolds could be promising for further research

scholarly journals Novel Structural Mechanism of Glutathione as a Potential Peptide Inhibitor to the Main Protease (Mpro): CoviD-19 Treatment, Molecular Docking and SAR Study

2020 ◽  
Author(s):  
abde lina ◽  
Khedidja BENAROUS ◽  
Mohamed Yousfi
Keyword(s):  
Molecular Docking ◽  
Pantothenic Acid ◽  
Vitamin B1 ◽  
Docking Study ◽  
Binding Pocket ◽  
Molecular Docking Study ◽  
Structural Mechanism ◽  
Discovery Studio ◽  
Main Protease ◽  
Sar Study

2019-nCoV Coronavirus spread all over the world and obliged one billion people in open confinement, no treatments or vaccine have been yet found against this pandemic. The Main Protease (M<sup>pro</sup>) is an attractive drug target, because it is the essential protein for the virus invasion. This study aims to test in silico the effect of five vitamins and a natural antioxidant against M<sup>pro</sup>, using molecular docking study, with Autodock Vina and Discovery Studio visualizer softwares. The used inhibitors were chosen based on their beneficial properties such as Tocopherol (vitamin E), Thiamine (vitamin B1), Pantothenic acid (vitamin B5), Pyridoxine (vitamin B6), Biotin (vitamin B7), and Glutathione (GSH), the best inhibitor pose was chosen based on the repetition ratio (RR) and the minimum affinity energy value (MEV). The results show that Glutathione is the best inhibitor model among the other tested vitamins in the active site of M<sup>pro</sup> with a RR value of 94% and MEV of - 5.5 kcal/mol, the compatibility of Glutathione structure inside the binding pocket as a tripeptide model found to be similar to the native ligand of M<sup>pro</sup>. Moreover, Thiamine, Biotin, and Tocopherol are saved as satisfied inhibitors to M<sup>pro</sup>, Pyridoxine was the weakest inhibitor. Depending on this result, we recommend the use of Glutathione and vitamin B family as a supportive strategy for the treatment of COVID-19.<br>

scholarly journals Novel Structural Mechanism of Glutathione as a Potential Peptide Inhibitor to the Main Protease (Mpro): CoviD-19 Treatment, Molecular Docking and SAR Study

2020 ◽  
Author(s):  
abde lina ◽  
Khedidja BENAROUS ◽  
Mohamed Yousfi
Keyword(s):  
Molecular Docking ◽  
Pantothenic Acid ◽  
Vitamin B1 ◽  
Docking Study ◽  
Binding Pocket ◽  
Molecular Docking Study ◽  
Structural Mechanism ◽  
Discovery Studio ◽  
Main Protease ◽  
Sar Study

2019-nCoV Coronavirus spread all over the world and obliged one billion people in open confinement, no treatments or vaccine have been yet found against this pandemic. The Main Protease (M<sup>pro</sup>) is an attractive drug target, because it is the essential protein for the virus invasion. This study aims to test in silico the effect of five vitamins and a natural antioxidant against M<sup>pro</sup>, using molecular docking study, with Autodock Vina and Discovery Studio visualizer softwares. The used inhibitors were chosen based on their beneficial properties such as Tocopherol (vitamin E), Thiamine (vitamin B1), Pantothenic acid (vitamin B5), Pyridoxine (vitamin B6), Biotin (vitamin B7), and Glutathione (GSH), the best inhibitor pose was chosen based on the repetition ratio (RR) and the minimum affinity energy value (MEV). The results show that Glutathione is the best inhibitor model among the other tested vitamins in the active site of M<sup>pro</sup> with a RR value of 94% and MEV of - 5.5 kcal/mol, the compatibility of Glutathione structure inside the binding pocket as a tripeptide model found to be similar to the native ligand of M<sup>pro</sup>. Moreover, Thiamine, Biotin, and Tocopherol are saved as satisfied inhibitors to M<sup>pro</sup>, Pyridoxine was the weakest inhibitor. Depending on this result, we recommend the use of Glutathione and vitamin B family as a supportive strategy for the treatment of COVID-19.<br>

scholarly journals Molecular Docking Study of Quercetein Analogues for Treating Tumours

2019 ◽  
Vol 12 (4) ◽  
pp. 30-34
Author(s):  
S. Gejalakshmi ◽  
N. Harikrishnan
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Structural Diversity ◽  
Docking Study ◽  
Therapeutic Agents ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Drug Candidates ◽  
Drug Compounds ◽  
Scientific Task

Drug discovery leading to robust and viable lead candidate’s remains a challenging scientific task, which is the transition from a screening hit to a drug candidate, requires expertise and experience. Natural products and their derivatives have been recognized for many years as a source of therapeutic agents and of structural diversity. The present research attempts to describe the utilization of compounds derived from natural resources as drug candidates, with a focus on the success of these resources in the process of finding and discovering new and effective drug compounds, an approach commonly referred to as ―natural product drug discovery

scholarly journals Towards potential inhibitors of COVID-19 main protease Mpro by virtual screening and molecular docking study

2020 ◽  
Vol 14 (1) ◽  
pp. 1626-1636
Author(s):  
Moujane Soumia ◽  
Zaki Hanane ◽  
Moualij Benaissa ◽  
Filali Zegzouti Younes ◽  
Alem Chakib ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Potential Inhibitors

scholarly journals SYNTHESIS, ANTIMICROBIAL ACTIVITY AND MOLECULAR DOCKING STUDY OF SOME NEW N-BENZYL AND N-BENZOYL-3-INDOLYL HETEROCYCLES

2016 ◽  
Vol 8 (9) ◽  
pp. 224
Author(s):  
Heba M. Abo-salem ◽  
Anhar Abdel-aziem ◽  
Inas E. Islam ◽  
Mariam M. Yossef ◽  
Eslam R. El-sawy
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Dihydrofolate Reductase ◽  
Docking Study ◽  
Phenacyl Bromide ◽  
Antimicrobial Compounds ◽  
Molecular Docking Study ◽  
Enoyl Reductase ◽  
Wide Range

<p><strong>Objective: </strong>Chalcones are one of the major classes of the natural products, which display a wide range of pharmacological properties. Also, chalcones are well-known intermediates for synthesizing various heterocyclic compounds like pyrazoline and pyrimidine derivatives. The present work is designed to synthesize new 3-indolylheterocycles starting from <em>N</em>-benzyl and <em>N</em>-benzoyl-1<em>H</em>-indole-3-carboxaldehyds and evaluating theirs <em>in vitro</em> antimicrobial activity. In addition, the probability of the most promising antimicrobial compounds to inhibit ATPase, enoyl reductase and dihydrofolate reductase were studied theoretically <em>via </em>molecular docking.</p><p><strong>Methods</strong><strong>:</strong><strong> </strong>A new series of 3-indolylchalcones 2a,b were prepared and allowed to react with hydrazine hydrate, phenyl hydrazine, hydroxylamine, urea, thiourea and guanidine to afford the corresponding pyrazoles 3a,b-6a,b and pyrimidines derivatives 7a,b-9a,b. On the other hand, the reaction of 2a, b with malononitrile afforded 10a, b, which upon cyclo-condensation with formic acid, formamide, urea or thiourea yielded the fused pyrido [2,3-<em>d</em>]pyrimidine 11a,b-14a,b. Moreover, cyclo-condensation of 2a, b with thiosemicarbazide gave pyrazolin-1-carbothioamides 15a, b, which under cyclization with phenacyl bromide afforded thiazole derivatives 16a and 16b. While the reaction of 2a, b with cyano thioacetamide afforded 2-mercaptonicotinonitriles 17a, b. The reaction of 17a, b with some halo-compounds gave S-alkyl derivatives 18a-d and 19a-d, respectively,which under heating in the presence of piperidine gave the fused thienopyridines 20a-d and 21a-d, respectively. All the newly prepared compounds were evaluated for their <em>in vitro</em> antimicrobial activity. In addition, molecular docking study of the most promising antimicrobial compounds against ATPase, enoyl reductase and dihydrofolate reductase theoretically is discussed.</p><p><strong>Results: </strong>Compounds 17a and 17b were found to be the most potent compounds with MIC of 0.98, 0.49 and 0.98µg/ml against <em>S.</em><em> </em><em>pneumoniae</em><em> </em>(RCMB 010010), <em>E</em><em>. coli </em>(RCMB 010052) and <em>A.</em> <em>fumigatus</em> (RCMB 02568), respectively compare to the reference drugs. Also, compounds 17a and 17b exhibited good docking scores and could act as inhibitors of enzymes understudied.</p><p><strong>Conclusion: </strong>Further work is recommended to confirm the ability of compounds 17a and 17b to inhibit ATPase, enoyl reductase and dihydrofolate reductase in a specific bioassay.</p>

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