Biology subjects

Dwivedi, V. D.

Publications and source records attributed to Dwivedi, V. D..

5 recordsLinked to original sources

bioRxiv2025

Unlocking Antiviral Potentials of Traditional Plants: A Multi-Method Computational Study against Human Metapneumovirus (HMPV)

Human metapneumovirus (HMPV) remains a critical challenge in respiratory healthcare, particularly due to the lack of targeted antiviral therapies and vaccines. This study employs an integrative computational framework to identify and evaluate the antiviral potential of nature-based compounds derived from traditional medicinal plants. A suite of advanced methodologies, including virtual screening, molecular docking, molecular dynamics (MD) simulations, density functional theory (DFT) calculations, pharmacophore modeling, and ADMET profiling, was utilized to comprehensively analyze candidate compounds. Among the tested compounds, Glycyrrhizin exhibited exceptional properties, with a binding energy of -65.4 kcal/mol, eight stabilizing hydrogen bonds, and remarkable dynamic stability (RMSD 1.3 [A]). Similarly, Withaferin A demonstrated a binding energy of -63.7 kcal/mol and high pharmacokinetic potential. Quantum-level analyses revealed favorable electronic properties, while ADMET profiling confirmed the compounds safety and drug-like characteristics. These findings underscore the potential of traditional phytochemicals to serve as lead candidates in antiviral drug development. This research bridges the gap between traditional medicine and modern computational techniques, paving the way for innovative and efficient therapeutic strategies against HMPV.

bioinformatics↗

bioRxiv2025

Exploring FDA-Approved Antiviral Drugs for Human Metapneumovirus Treatment: Integrative Computational Insights

This study leverages advanced computational methodologies to identify potential antiviral therapies targeting human metapneumovirus (HMPV), focusing on FDA-approved antiviral drugs and control compounds. A comprehensive computational framework, encompassing virtual screening, molecular docking, molecular dynamics (MD) simulations, density functional theory (DFT) analysis, and ADMET profiling, was employed. Key findings highlight Remdesivir and Peramivir as the most promising candidates, with superior binding energies (-9.5 kcal/mol and - 9.2 kcal/mol, respectively), stable interaction profiles, and robust pharmacological properties. Molecular dynamics revealed exceptional stability for Remdesivir, with the lowest RMSD (0.20 nm), and pharmacophore analysis emphasized its strong hydrogen bonding and hydrophobic interactions. ADMET profiling confirmed their high bioavailability (85% {+/-} 3 for Remdesivir) and low toxicity, positioning these drugs for repurposing against HMPV. This integrative study underscores the potential of computational tools in streamlining drug discovery and advancing therapeutic interventions.

bioinformatics↗

bioRxiv2025

Repurposing Metal-Based Therapeutics for Human Metapneumovirus (HMPV): An Integrative Computational Approach

Human metapneumovirus (HMPV) poses a significant global health challenge, with limited therapeutic options available. This study employs a comprehensive computational framework to repurpose metal-based drugs as potential HMPV inhibitors. A library of compounds was systematically evaluated using virtual screening, high-precision molecular docking, molecular dynamics (MD) simulations, density functional theory (DFT) calculations, molecular electrostatic potential (MESP) mapping, and pharmacophore modeling. Key candidates, including Auranofin, Silver Sulfadiazine, and Gallium Nitrate, demonstrated high binding affinities ({Delta}Gbinding: -68.5 to -62.7 kcal/mol) and favorable stability metrics (RMSD: 2.1-2.4 [A]). ADME-toxicity (ADMET) profiling highlighted Auranofins robust bioavailability (80%) and extended half-life (8.5 hours), while Ribavirin and Favipiravir emerged as safe controls with minimal toxicity. Quantum chemical analyses reinforced the compounds electronic stability and reactivity. This integrative study provides a promising avenue for repurposing existing therapeutics, bridging computational insights with translational potential to combat HMPV.

bioinformatics↗

bioRxiv2025

Harnessing Computational Insights to Identify Potent Inhibitors for Human Metapneumovirus (HMPV): A Synergistic Approach with Natural Compounds

Human metapneumovirus (HMPV), a leading cause of acute lower respiratory tract infections, has emerged as a global health challenge due to its high prevalence, particularly among children, the elderly, and immunocompromised individuals. Despite its significant impact, no targeted antivirals or vaccines are available. This study employs a comprehensive computational pipeline to identify and evaluate potential inhibitors of the HMPV matrix protein (PDB: 5WB0). Natural compounds such as epigallocatechingallate (EGCG), rutin, and quercetin, along with control drugs, were screened for their therapeutic potential.Virtual screening identified EGCG (-9.1 kcal/mol), rutin (-9.0 kcal/mol), and quercetin (-8.8 kcal/mol) as top binders, surpassing standard drugs like ribavirin (-8.9 kcal/mol). Molecular docking revealed stable binding interactions, including hydrogen bonding with residues Arg143 and Glu186. Molecular dynamics (MD) simulations over a 1000 ns trajectory confirmed the stability of these complexes, with EGCG displaying the lowest RMSD (2.1 [A]) and consistent hydrogen bonding throughout the simulation. Density Functional Theory (DFT) calculations highlighted favorable electronic properties, with EGCG showing a low band gap (3.29 eV) and high dipole moment (3.12 D), indicative of strong reactivity and binding potential. ADMET profiling revealed excellent oral bioavailability for EGCG (84%) and quercetin (88%), with minimal toxicity risks. The Molecular Electrostatic Potential (MESP) mapping identified highly reactive regions on the molecular surface, correlating with nucleophilic and electrophilic binding capabilities. The findings position EGCG, rutin, and quercetin as promising candidates for HMPV therapy, providing a strong foundation for further experimental validation and preclinical development.

bioinformatics↗

bioRxiv2021

Mechanistic insights into the Japanese Encephalitis Virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica

Japanese encephalitis (JE) virus, belongs to the genus flavivirus, is a major cause of viral encephalitis, which results in neurological damage. RNA-dependent RNA polymerase (RdRp) protein is the sole enzyme responsible for viral genome replication in RNA viruses and serves as an excellent target for anti-viral therapeutic development, as its homolog is not present in humans. In this study, the crystal structure of JE RNA-dependent RNA polymerase (jRdRp) protein was obtained from protein data bank while 43 by bioflavonoids reported in Azadirachta indica were retrieved from the PubChem database. Following, structure based virtual screening was employed using MTiOpenScreen server and top four compounds, viz. Gedunin, Nimbolide, Ohchinin acetate, and Kulactone, with the most negative docking scores (> -10 kcal/mol) conformations were redocked using AutoDock Vina; these complexes showed mechanistic interactions with Arg474, Gly605, Asp668, and Trp800 residues in the active site of jRdRp protein against reference ligand, i.e., Guanosine-5-Triphosphate. Furthermore, 100 ns classical molecular dynamics simulation and binding free energy calculation showed considerable stability (via hydrogen bonding and hydrophobic interactions) of docked bioflavonoids in the active pocket of jRdRp and significant contribution of van der Waals interactions for docked complex stability during simulation, respectively. Therefore, the outcome of this study predicted the substantial anti-viral activity of Gedunin, Nimbolide, Ohchinin acetate, and Kulactone against jRdRp protein and can be considered for further antiviral drug development.

bioinformatics↗