Biswa Ranjan Meher

Hepatitis C virus (HCV) remains a major global health concern, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), with an estimated 185 million people affected worldwide. In the absence of an FDA-approved vaccine, the development of effective antiviral strategies remains essential. The HCV NS3-4A protease, which mediates cleavage of the viral polyprotein at specific downstream sites of NS3 and is essential for replication-complex formation, represents a key therapeutic target. In this study, approximately 1,480 phytocompounds were compiled from the IMPPAT database and previously reported in vitro studies and subjected to drug-likeness, toxicity, and biological activity screening using pkCSM, SwissADME, and PASS. Twenty compounds were subsequently prioritized and docked against WT, R155K, and D168Y NS3/4A protease structures. Among these, Ladanein (LAD) and Diosmetin (DMT) exhibited favourable binding across all protein variants. MD simulations indicated stable protein–ligand interactions, while MM/GBSA calculations revealed more favourable binding free energies for LAD than DMT across the WT and mutant complexes. Residue-wise energy decomposition identified more energetically favourable hotspot residues in LAD-bound complexes, whereas DMT exhibited higher overall hydrogen-bond occupancy. PCA and free-energy landscape analyses further demonstrated ligand-dependent alterations in collective conformational states induced by the R155K and D168Y substitutions. Overall, these findings computationally prioritize LAD as a promising candidate against WT and mutant HCV NS3/4A protease, warranting further in vitro and biochemical validation. Graphical abstract

Dengue fever (DF) is a worldwide health hazard with no known cure yet. Screenings of synthetic, animal‐derived, and phytocompounds for Dengue virus (DENV) targets have yielded no successful antivirals to date. The present investigation examines medications that act as antagonists of the NS2B‐NS3 protease (NS2B‐NS3 ^Pro ), a potential therapeutic target for DF. Plectasin (PLS) is an antiviral peptide derived from the venom of Pseudoplectania nigrella , a deadly fungus. Previous in vitro studies found that the peptide PLS inhibits DENV‐2 NS2B‐NS3 ^Pro activity. The current in silico research demonstrates the anti‐dengue properties of PLS for the wild‐type (WT) and its two primary mutants (H51N and S135A) of the DENV‐2 NS2B‐NS3 ^Pro in the active‐site region. The peptide toxin (PLS) and the three NS2B‐NS3 ^Pro proteases (WT, H51N, and S135A) were docked by considering their respective active sites. Cluspro‐2 quantifies efficacy, inhibitory consistency, and peptide binding affinity using rigid‐flexible docking. Given the ligand's high binding affinity, docking score, and molecular interaction network, molecular dynamics (MD) simulations and molecular mechanics Generalized‐born surface area (MM‐GBSA)‐based free energy calculations were used to assess the stability of the NS2B/NS3 ^Pro ‐PLS complexes. Anti‐dengue compounds derived from fungal toxins, when screened using computer models, showed promising results. This research is crucial to finding the best treatment for dengue using fungal toxins.

1. The conversion of metabolites for final cellular functions in plants depends on the precise regulation of enzymatic activities in time and space. Through the coordinated action of specific amino...

Chikungunya virus (CHIKV) remains a significant global health threat due to recurrent outbreaks and the lack of approved antiviral therapies. The viral non‐structural protein 2 (nsP2) protease, which is crucial for viral replication and immune evasion, is a promising drug target. In this study, an integrated computational approach combining virtual screening, molecular docking, molecular dynamics (MD) simulations, and quantum chemical analysis (DFT) was employed to identify phytochemical inhibitors of CHIKV nsP2. A library of 5000 antiviral phytochemicals was filtered using drug‐likeness and ADMET criteria, yielding 17 candidates for docking. Protocol validation using known inhibitors (E‐64 and Ribostamycin sulfate) produced RMSD values <2.5 Å. Isorhamnetin (−8.7 kcal/mol) and apigenin (−8.2 kcal/mol) showed strong binding affinity and stable interactions with the catalytic dyad (Cys478–His548). Alanine mutagenesis confirmed the importance of these residues. MD simulations demonstrated structural stability and favorable binding energies, with isorhamnetin exhibiting superior performance. DFT analysis revealed enhanced electronic adaptability of isorhamnetin, supporting its binding efficiency. Overall, isorhamnetin emerges as a promising natural scaffold for nsP2 inhibition, warranting further experimental validation.

A green, sustainable, and ultrasonication assisted synthesis of functionalized 2‐aryldihydroperimidines have been achieved in excellent yields (up to 96%) from 1,8‐diaminonaphthalene and aryl/heteroaryl aldehydes employing naturally occurring bioorganic taurine catalyst in ethanol at ambient temperature. The method offers facile synthesis of 2‐aryldihydroperimidines and products isolation in green and sustainable approach (column chromatography‐free). In the present study, the 2‐aryldihydroperimidines upon docking and MD simulation revealed that 3f and 3p exhibit strong binding affinity and structural stability when bound to CHIKV nsP2 and DENV NS2B‐NS3 protease, respectively. Hotspot residue analysis showed key interactions between the 2‐aryldihydroperimidines and critical residues within the active sites of both CHIKV nsP2, DENV NS2B‐NS3 proteases, emphasizing the inhibitory potential of the compounds.

Herein, we report a photocatalyst (PC)-free, visible-light (30 W LED)-driven green and sustainable synthesis of a series of functionalized tetraketones by a one-pot multicomponent reaction at room temperature. The ethanol-mediated reaction of variably substituted aromatic/heteroaromatic, aliphatic aldehydes, and dimedone furnished the biologically relevant tetraketones in very good yields (72-92%) in 10 min to 5 h. The key advantages of the current process include its environmentally benign aspect, operational simplicity, easy isolation of the products, high yields, PC- and metal-free aspects, employment of visible light as a green and sustainable energy source, and gram-scale synthesis. The synthesized tetraketones are further subjected to in silico studies which investigate the potential of synthesized tetraketones as inhibitors targeting CHIKV nsP2 and DENV NS2B-NS3 viral proteases through a combination of virtual screening, molecular docking, and MD simulation studies. We evaluated the binding affinity and inhibitory efficacy of the synthesized tetraketones against the viral proteases: CHIKV nsp2 and DENV NS2B-NS3. Pleasingly, our findings demonstrate that compound 3f exhibits promising inhibitory activity, with binding affinities of -24.22 and -29.39 kcal/mol for CHIKV nsp2 and DENV NS2B-NS3 protease, respectively. This result highlights the potential of tetraketones as novel antiviral agents against CHIKV and DENV.

One-pot catalyst-free light-driven multicomponent synthesis of benzopyrans and in silico studies on Chikungunya and Zika viruses have been reported.

Dengue fever is one of the most dreaded viral diseases caused by the bite of female Aedes aegypti and Aedes albopictus mosquitoes infected with the Dengue virus (DENV). No DENV antiviral drugs have been approved, yet they are desperately needed. The current study focuses on finding potential therapeutics from 8 medicinal plants reported to have activity against the DENV NS2B/NS3 protease in vitro. Eighty‐two phytocompounds were selected from eight different medicinal plants like Vernonia cinerea, Tridax procumbens, Cassia angustifolia, Lawsonia inermis, Dryobalanops aromatic, Punica granatum, Zingiber zerumbet and Zizyphus‐jujuba . The top five phytocompounds (Epicatechin (EPI), Chrysoeriol (CHR), Apigenin (API), Quercetin‐3,4′‐Dimethylether (QUE), and Caffeic acid (CAF)) identified from toxicity evaluation and docking studies were further subjected to 100 ns long Molecular Dynamics (MD) simulations to study their structural stability and binding affinity through MM‐PBSA based free‐energy calculations. MD results revealed overall conformational stability with all the five phytocompounds. Furthermore, MM‐PBSA results suggest binding free energy values of −154.415 kJ/mol, −151.154 kJ/mol, −139.048 kJ/mol, −122.827 kJ/mol), and −120.622 kJ/mol for compound EPI, QUE, API, CAF, and CHR respectively by interacting with essential binding site residues. These compounds could thus be studied extensively to develop nature‐based therapeutic compounds as anti‐dengue agents for DENV2.