Identification of Antiviral Drug Candidates Against Monkeypox DNA Polymerase and Profilin-like Protein A42R Utilizing anIn-SilicoApproach DOI Open Access
Muhammad Waqas Amjid,

Muhammad Maroof Khan,

Stephen F. Pastore

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

ABSTRACT Monkeypox virus (MPXV) is emerging as a major concern in the field of infectious diseases. Current treatments are limited, highlighting need for new therapeutic options. The use computational methods, such molecular docking and dynamic (MD) simulations, valuable approach identifying potential compounds that can target specific proteins virus, like DNA polymerase profilin-like protein A42R this case, with aim controlling disease. Our study focused on screening various libraries predicted binding to MPXV DPol proteins, top-performing molecules identified based their scores. Among these, Dorsilurin K Mangostin complex DPol, whereas [2-oxo-2-[3-(3,4,5,6-tetrahydro-2H-azepin-7-ylsulfamoyl)anilino]ethyl] 3,5-dimethylbenzoate N-[4-[2-[4-(4-methylphenyl)sulfonylpiperazin-1-yl]-2-oxoethoxy]phenyl]furan-2-carboxamide stand out notably high scores, suggesting they may have good affinity respectively. MD simulations confirmed stability these ligand-protein complexes followed by evaluation ADMET oral bioavailability analysis. However, it important methods suggest promising candidates, vitro eventually vivo studies essential validate candidates. Further will provide insights into efficacy, safety, side effects. In conclusion, offers avenues developing Monkeypox. If prove effective further studies, could be significant breakthrough managing zoonotic

Language: Английский

Predictive Modelling in pharmacokinetics: from in-silico simulations to personalized medicine DOI
Ajita Paliwal, Smita Jain, Sachin Kumar

et al.

Expert Opinion on Drug Metabolism & Toxicology, Journal Year: 2024, Volume and Issue: 20(4), P. 181 - 195

Published: March 14, 2024

Pharmacokinetic parameters assessment is a critical aspect of drug discovery and development, yet challenges persist due to limited training data. Despite advancements in machine learning in-silico predictions, scarcity data hampers accurate prediction candidates' pharmacokinetic properties.

Language: Английский

Citations

8
In-silico repurposing of antiviral compounds against Marburg virus: a computational drug discovery approach DOI
Rahul Kumar Singh, Kaushik Sarkar, Rajesh Kumar Das

et al.

In Silico Pharmacology, Journal Year: 2025, Volume and Issue: 13(1)

Published: March 6, 2025

Language: Английский

Citations

0
Role of structure-based drug design (SBDD) in the repurposing and discovery of anti-viral leads against Monkeypox virus disease DOI Creative Commons

Jihane Touhtouh,

Fettouma Chraa,

Doha El Meskini

et al.

Results in Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 102317 - 102317

Published: May 1, 2025

Language: Английский

Citations

0
Development of newer generation Vascular endothelial growth factor Receptor-2 Inhibitors: Pharmacophore based design, virtual Screening, molecular Docking, molecular dynamic Simulation, and DFT analyses DOI Creative Commons

Mubarak A. Alamri,

Mohammed Merae Alshahrani, Abdullah S. Alawam

et al.

Journal of King Saud University - Science, Journal Year: 2024, Volume and Issue: 36(8), P. 103285 - 103285

Published: June 5, 2024

Vascular Endothelial Growth Factor (VEGF) has a greater impact on carcinogenesis, and it is the most significant receptor in mediating mutagenesis permeability of endothelial cells. Here, we report identification potential VEGFR-2 inhibitors as new putative anti-cancer agents. In this regard, pharmacophore model was generated, considering established potent VEGFR2 inhibitors. This further applied for virtual screening ZINC database feature-based design another eight molecules (B1–B8). Examining these using sequential computational approaches including molecular docking, dynamic simulation, DFT analysis leads to compounds B3, B5, B7 that showed better binding affinity, stability, interaction mechanisms concerning reference control, Sorafenib. Further, Lipinski rule filters ADMET support selected drug candidates subjected experimental validation.

Language: Английский

Citations

3
Structure-based discovery of F. religiosa phytochemicals as potential inhibitors against Monkeypox (mpox) viral protein DOI Creative Commons
Ranjan K. Mohapatra, Ahmed Mahal, Pranab Kishor Mohapatra

et al.

Journal of Biosafety and Biosecurity, Journal Year: 2024, Volume and Issue: 6(3), P. 157 - 169

Published: June 24, 2024

Outbreaks of Monkeypox (mpox) in over 100 non-endemic countries 2022 represented a serious global health concern. Once neglected disease, mpox has become public issue. A42R profilin-like protein from (PDB ID: 4QWO) represents potential new lead for drug development and may interact with various synthetic natural compounds. In this report, the interaction six phytochemicals found medicinal plant Ficus religiosa (abundant India) was examined. Based on predicted compared protein-ligand binding energies, biological properties, IC50 values toxicity, two compounds, kaempferol (C-1) piperine (C-4), were selected. ADMET characteristics quantitative structure-activity relationship (QSAR) these compounds determined, molecular dynamics (MD) simulations performed. silico examination (C-4) interactions gave best-pose ligand-binding energies –6.98 –5.57 kcal/mol, respectively. The C-1 7.63 μM 82 C-4. Toxicity data indicated that are non-mutagenic, QSAR revealed piperlongumine (5.92) (5.25) had higher log P than other MD complex C-4 performed to examine stability ligand-protein interactions. As showed highest affinity activities, they be suitable candidates developing therapeutic drugs. This study should facilitate discovering synthesizing innovative therapeutics address infectious diseases.

Language: Английский

Citations

3
Explication of Pharmacological Proficiency of Phytoconstituents from Adansonia digitata Bark: An In Vitro and In Silico Approaches DOI Creative Commons

P. Sangavi,

Gowtham Kumar Subbaraj, K. T. Nachammai

et al.

Scientifica, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

Compared to other drug discovery sources, traditional medicine has significantly contributed developing innovative therapeutic molecules for preventive and curative medicine. The Baobab tree, also known as Adansonia digitata L., is significant in Africa due its multitude of benefits various parts that serve different purposes, providing economic support rural communities. analysis a plant sample using Fourier transform infrared (FT‐IR) spectroscopy detected multiple functional groups, such carboxyl aromatic groups. Additionally, gas chromatography‐mass (GC‐MS) was utilized identify compounds present the sample, including tetrachloroethylene octyl ester. results assays, α ‐diphenyl‐ β ‐picrylhydrazyl (DPPH), superoxide, nitric oxide scavenging total antioxidant by thiobarbituric acid method (TBA) ferric thiocyanate (FTC) method, demonstrated substantial free radicals an effective efficacy. bark’s antimicrobial activity tested through agar diffusion, resulting range zone inhibition from 10.1 ± 0.36 mm 20.85 0.76 mm. minimum inhibitory concentration (MIC) value observed be approximately 0.625 µ g/mL. biofilm percentage ranged 9.89% 57.92%, with highest being 57.92%. GC‐MS FT‐IR studies revealed phytocompounds, which were then analyzed their potential properties. Computational conducted on phytocompounds against Pseudomonas aeruginosa C2 kinase (antioxidant). study concluded bark extract phytocompound have efficacy target proteins. best docking scores about −7.053 kcal/mol −7.573 (antioxidant), respectively. interaction patterns crucial amino residues elucidate phytocompounds.

Language: Английский

Citations

3
Interplay of precision therapeutics and MD study: Calocybe indica's potentials against cervical cancer and its interaction with VEGF via octadecanoic acid DOI Creative Commons
Suhana Datta, Preeti Verma, Bikram Dhara

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(8)

Published: April 1, 2024

The evolving landscape of personalized medicine necessitates a shift from traditional therapeutic interventions towards precision-driven approaches. Embracing this paradigm, our research probes the efficacy aqueous crude extract (ACE) Calocybe indica in cervical cancer treatment, merging botanical insights with advanced molecular research. We observed that ACE exerts significant influences on nuclear morphology and cell cycle modulation, further inducing early apoptosis showcasing prebiotic attributes. Characterization have identified several phytochemicals including presence octadeconoic acid. Simultaneously, utilizing Molecular Dynamics (MD) simulations, we deciphered intricate interactions between Vascular Endothelial Growth Factor (VEGF) Octadecanoic acid to establish C.indica's role as an anticancer agent. Our study delineates acid's potential robust binding partner for VEGF, comprehensive analyses RMSD RMSF profiles highlighting stability adaptability protein-ligand interactions. Further in-depth thermodynamic explorations via MM-GBSA calculations reveal VEGF-Octadecanoic complex. Emerging innovations, encompassing proteolysis-targeting chimeras (PROTACs) avant-garde nanocarriers, are discussed context their synergy compounds like P&C. This convergence underscores profound awaiting clinical exploration. offers holistic perspective promising avenues facilitated by C. against cancer, intricately woven prospective integration precision therapeutics modern oncology.

Language: Английский

Citations

2
Phytochemical stimulants for cancer therapeutics from Garcinia gummi-gutta: A prime research report DOI

B. V. Vibala,

P.K. Praseetha,

S. Vijayakumar

et al.

Gene Reports, Journal Year: 2024, Volume and Issue: 34, P. 101885 - 101885

Published: Jan. 22, 2024

Language: Английский

Citations

1
Unlocking the Secret Vault of Promising Drug Targets from Mpox Proteome- A Computational Approach DOI Creative Commons
Harshit Tiwari, Shreya Sharma,

Anchal Dixit

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 6, 2024

Abstract Mpox (previously known as Monkeypox) is an infectious disease caused by the monkeypox virus that can be lethal and a serious hazard to public health. Despite various efforts develop effective drugs vaccines, presently there are relatively few antiviral therapeutics available specific disease. The knowledge of possible drug targets in proteome enhance tailored needs. With this objective, present study uses computational approaches identify analyze putative therapeutic within viral proteome. A total 33 promising were identified critical for survival replication following in-depth analysis virus. Using array explorations, structural functional characteristics analyzed gain insights into their mechanisms action. Our findings indicate several have potential development treatments against In conclusion, provides comprehensive proteome, identifying prospective treatment. These developing novel highly potentially

Language: Английский

Citations

1
Exploring the efficacy of 1-amino-cyclopropane-1-carboxylic acid (ACCA) as a natural compound in strengthening maize resistance against biotic and abiotic stressors: an empirical computational study DOI Creative Commons
Sandip Debnath, Abdallah M. Elgorban, Ali H. Bahkali

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 11, 2023

This study aims to understand plant-bacteria interactions that enhance plant resistance environmental stressors, with a focus on maize (

Language: Английский

Citations

3