Journal of Applied Organometallic Chemistry

Molecular Docking, Molecular Dynamics Simulation, and MM/GBSA Studies of (N-(4-Carbamoylphenyl)-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxamide for Its Potential Use Against SARS-CoV-2

Emmanuel Israel Edache; Adumu Uzairu; Paul Andrew Mamza; Gideon Adamu Shallangwa; Muhammad Tukur Ibrahim

Volume 3, Issue 4 , November 2023, , Pages 321-345

https://doi.org/10.48309/jaoc.2023.423447.1135

Abstract

Coronavirus disease 2019 (COVID-19) is a pandemic disease caused by the SARS-coronavirus-2, which has a high rate of infection. Regardless of the advancements made in the creation of ... Read More Coronavirus disease 2019 (COVID-19) is a pandemic disease caused by the SARS-coronavirus-2, which has a high rate of infection. Regardless of the advancements made in the creation of vaccines, it is urgently necessary to identify antiviral substances that can more effectively combat the SARS-coronavirus-2. The SARS-coronavirus-2 main protease is essential for viral transcription and replication. Using molecular docking, molecular dynamics simulation, and free binding energy calculations based on molecular mechanics/generalized Born surface area (MM/GBSA) approaches, an in silico technique was used in this study to help clarify the inhibitory potential of (N-(4-carbamoylphenyl)-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxamide (aka, compound 36) against the main protease of SARS-coronavirus-2. Four software programs: AutoDockFR, AutoDock Vina v1.2.3, CABS-Flex2.0, and fastDRH servers were used to investigate the proteins binding sites, docked the ligands into the crystal structure of SARS-coronavrus-2 Mpro, check the stability of the complexes using molecular dynamics simulations, and MM/GBSA calculations, respectively. The standard drugs have all shown positive interactions with the main protease of the virus, but compound 36 has the highest negative binding affinity of them all. Computer-aided drug design was used to create a few compound 36 derivatives, and pharmacokinetic studies and molecular docking studies were conducted to assess their drug-like characteristics. These compounds (D3 and D6) have better binding affinities than the template and the conventional drugs. The top-scoring conformational complexes were subjected to molecular dynamics (MD) simulations in the following section of the study to further examine the complexes stability and the interactions between the ligand and receptor. The MM/GBSA further demonstrated that net free binding energies were primarily raised by Van der Waals interactions. The present investigation serves as a foundation for investigating the improved binding capacities and structural characteristics of SARS-CoV-2 Mpro variants to develop fresh anti-viral drugs.

In Silico Molecular Docking Against-KIT Tyrosine Kinase and ADME Studies of 4-Thiazolidinone Derivatives

Deepak Shankar Kadam; Sudhakar G Patil; Denni Mammen; Shreyash Deepak Kadam; Vijaykumar Shivdas More

Volume 3, Issue 1 , January 2023, , Pages 13-27

https://doi.org/10.22034/jaoc.2023.355363.1058

Abstract

Thiazolidin-4-one derivatives have been hailed as “wonder nucleus” due to their profound biological activities. A number of derivatives with variable functional groups attached ... Read More

In Silico Estrogen Receptor Activity Evaluation of Some β-Carboline Derivatives Through Molecular Docking Approach and Target Prediction by ADME Study

Bapusaheb S. Wadje; Devidas Pawar; Swapnil Navhate; Vijay N Bhosale,

Volume 3, Issue 1 , January 2023, , Pages 28-38

https://doi.org/10.22034/jaoc.2023.356944.1060

Abstract

A series of β-carboline derivatives have been modified at C-1 sites of the aryl ring and tested for the Insilco Estrogen Receptor inhibitory study. all the designed molecules show ... Read More

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Keywords = ADME

Molecular Docking, Molecular Dynamics Simulation, and MM/GBSA Studies of (N-(4-Carbamoylphenyl)-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxamide for Its Potential Use Against SARS-CoV-2

Abstract

In Silico Molecular Docking Against-KIT Tyrosine Kinase and ADME Studies of 4-Thiazolidinone Derivatives

Abstract

In Silico Estrogen Receptor Activity Evaluation of Some β-Carboline Derivatives Through Molecular Docking Approach and Target Prediction by ADME Study

Abstract