In silico screening, ADMET analysis and MD simulations of phytochemicals of Onosma bracteata Wall. as SARS CoV-2 inhibitors

Vegad, Udaykumar G; Gajjar, Normi D.; Nagar, Prinsa R.; Chauhan, Sanjay P; Pandya, Devang J.; Dhameliya, Tejas M.

doi:10.1007/s13205-023-03635-7

Cited by 5 publications

(2 citation statements)

References 48 publications

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“…Towards the on‐going research endeavors on in silico molecular modeling [27–35] and anti‐malarial agents, [36] we have performed a computational search of 170,269 compounds through Asinex BioDesign library 2021.02 through molecular docking using AutoDock Vina against wild‐type Pf DHFR‐TS (1J3I). This was followed by an evaluation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, certain filters for drug likeliness assessment, and molecular dynamics (MD) simulations of the most promising compounds were performed.…”

Section: Introductionmentioning

confidence: 99%

Investigation on Anti‐plasmodial Agents Against wild‐type PfDHFR Through In Silico Computational Tools

Parikh,

Pandya,

Salaria

et al. 2024

ChemistrySelect

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Malaria is the most severe and common parasitic infection, with P. falciparum responsible for the majority of cases and deaths each year. As anti‐malarial drug resistance continues to increase, novel compounds with anti‐ P. falciparum activity must be identified. In search of a new molecule to cure the resistant malarial parasite, a total of 1,70,269 ligands from the Asinex BioDesign library 2021.2 were virtually screened using AutoDock Vina against wild‐type P. falciparum dihydrofolate reductase‐thymidylate synthase (PfDHFR‐TS). The computational molecular modeling investigations indicated the discovery of seventeen new compounds (2‐18) with higher binding energy compared to the PfDHFR‐TS inhibitor, pyrimethamine (1). Furthermore, the study employing drug‐likeness criteria and their ADMET profile suggested that these hits were the most promising drug candidates due to higher absorption and druggability. Furthermore, GROMACS 2023.4 was used to perform the molecular dynamics simulations on the foremost compound (2) having sufficient stability, leading to a key step towards the search of novel PfDHFR‐TS inhibitors against malaria.

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Section: Introductionmentioning

confidence: 99%

Investigation on Anti‐plasmodial Agents Against wild‐type PfDHFR Through In Silico Computational Tools

Parikh,

Pandya,

Salaria

et al. 2024

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“…Regarding the possible treatments for this disease, research has mainly focused on the invention of potential vaccines or designing potential drugs ( Liu et al, 2020 ; Jaan et al, 2021 ; Shah et al, 2024 ). So far, not even a single drug has been discovered or formulated specifically for the treatment of COVID-19 ( Vegad et al, 2023 ). Some FDA-approved antiviral drugs, like remdesivir, chloroquine, ribavirin, hydroxychloroquine, favipiravir, and lopinavir, among others, were found to provide partial relief from the deadly virus ( Jean and Hsueh, 2020 ; Wu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Identifying plant-derived antiviral alkaloids as dual inhibitors of SARS-CoV-2 main protease and spike glycoprotein through computational screening

Yamin,

Ahmad,

Khalid

et al. 2024

Front. Pharmacol.

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COVID-19 is currently considered the ninth-deadliest pandemic, spreading through direct or indirect contact with infected individuals. It has imposed a consistent strain on both the financial and healthcare resources of many countries. To address this challenge, there is a pressing need for the development of new potential therapeutic agents for the treatment of this disease. To identify potential antiviral agents as novel dual inhibitors of SARS-CoV-2, we retrieved 404 alkaloids from 12 selected medicinal antiviral plants and virtually screened them against the renowned catalytic sites and favorable interacting residues of two essential proteins of SARS-CoV-2, namely, the main protease and spike glycoprotein. Based on docking scores, 12 metabolites with dual inhibitory potential were subjected to drug-likeness, bioactivity scores, and drug-like ability analyses. These analyses included the ligand–receptor stability and interactions at the potential active sites of target proteins, which were analyzed and confirmed through molecular dynamic simulations of the three lead metabolites. We also conducted a detailed binding free energy analysis of pivotal SARS-CoV-2 protein inhibitors using molecular mechanics techniques to reveal their interaction dynamics and stability. Overall, our results demonstrated that 12 alkaloids, namely, adouetine Y, evodiamide C, ergosine, hayatinine, (+)-homoaromoline, isatithioetherin C, N,alpha-L-rhamnopyranosyl vincosamide, pelosine, reserpine, toddalidimerine, toddayanis, and zanthocadinanine, are shortlisted as metabolites based on their interactions with target proteins. All 12 lead metabolites exhibited a higher unbound fraction and therefore greater distribution compared with the standards. Particularly, adouetine Y demonstrated high docking scores but exhibited a nonspontaneous binding profile. In contrast, ergosine and evodiamide C showed favorable binding interactions and superior stability in molecular dynamics simulations. Ergosine demonstrated exceptional performance in several key pharmaceutical metrics. Pharmacokinetic evaluations revealed that ergosine exhibited pronounced bioactivity, good absorption, and optimal bioavailability. Additionally, it was predicted not to cause skin sensitivity and was found to be non-hepatotoxic. Importantly, ergosine and evodiamide C emerged as superior drug candidates for dual inhibition of SARS-CoV-2 due to their strong binding affinity and drug-like ability, comparable to known inhibitors like N3 and molnupiravir. This study is limited by its in silico nature and demands the need for future in vitro and in vivo studies to confirm these findings.

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Recent Advancements and Developments of Molecular Dynamics Simulations in the Discovery of Anti‐protozoal Agents

Dhameliya,

Vekariya,

Vaddoriya

et al. 2024

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Molecular dynamics simulations have been developed as the most powerful tool in the field of computational chemistry for the discovery of novel anti‐protozoal agents against malaria. In this review, the recent advancements and developments in the field of molecular dynamics simulations driven identification and optimization of promising anti‐protozoal agents have been highlighted along with the use of advanced simulation softwares, energy calculations, stability parameters, and many more. To the best of our knowledge, the present work has been the first review article to highlight the use of molecular dynamics simulations for the discovery of anti‐plasmodial agents with the aim to dig out the significant insights into the simulations having the applications for the benefit of computational and medicinal chemists.

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In silico screening, ADMET analysis and MD simulations of phytochemicals of Onosma bracteata Wall. as SARS CoV-2 inhibitors

Cited by 5 publications

References 48 publications

Investigation on Anti‐plasmodial Agents Against wild‐type PfDHFR Through In Silico Computational Tools

Investigation on Anti‐plasmodial Agents Against wild‐type PfDHFR Through In Silico Computational Tools

Identifying plant-derived antiviral alkaloids as dual inhibitors of SARS-CoV-2 main protease and spike glycoprotein through computational screening

Recent Advancements and Developments of Molecular Dynamics Simulations in the Discovery of Anti‐protozoal Agents

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