Monkeypox virus is a zoonotic virus of the genus Orthopox viruses. It can be transmitted through direct or indirect contact with animals or infected ones. Owing similarity of pathogenesis with smallpox, the same drugs can be used for both viruses, but they are not specific and only help to relieve the symptoms only. Therefore, the absence of antiviral treatment or licensed vaccine highlights an urgent need, especially due to its rapid prevalence. The study screened the library of compounds to retrieve drug-like molecules that can act against monkeypox virus. The highly virulent target gene B8R having uniport ID Q3I8J0 was chosen. Targeting B8R is substantial for global health and can align with SDG 3 and awareness of disease management. The B8R was modelled via Artificial intelligence (AI) AlphaFold method and then exposed to a library of compounds. Complementary interactions in the active site were shown by molecular docking. The Complex-1 had the greatest binding affinity (–8.4 kcal/mol), followed by Complex-2 (–8.1 kcal/mol) and Complex-3 (–7.7 kcal/mol). After 125 ns, Complex-1 reached equilibrium at 7.5 Å RMSD, according to MD simulations, exhibiting stable ligand retention and reliable interactions with crucial residues Gly135 and Lys136. Complex-3 shown intermediate protein stability (6 Å RMSD) but notable ligand fluctuation (48 Å RMSF), while Complex-2 displayed increased protein RMSD (8 Å RMSD) and delayed ligand stabilisation (16 Å RMSF). These results were corroborated by PCA analysis, which showed that Complex-1 exhibits coherent structural development whereas Complex-2 and Complex-3 show scattered and compact trajectories, respectively. Complex-1 promise for Mpox viral inhibition was highlighted by the fact that it was the most stable and dynamically favourable contender overall. The N-terminal follows the folding trend. The insilico analysis not only proposed a potent compound but also provides deep insight into the behavior of protein. The proposed potent compound against this zoonotic virus can be helpful to combat the monkeypox virus by subjecting it further towards experimental investigation.

Background: Current antivirals for orolabial Herpes simplex virus type 1 (HSV-1) often provide incomplete suppression and limited reactivation control, sustaining recurrent oral lesions and inflammation that compromise oral health. HSV-1 subverts host signaling networks to enhance its replication and trigger inflammation. Among these, the extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways are hijacked to facilitate viral gene expression and cell survival. Objectives: In this study, we employed U0126 [a mitogen-activated protein kinase 1/2 (MEK1/2) inhibitor] and LY294002 [a phosphatidylinositol 3-kinase (PI3K) inhibitor] as targeted pharmacological tools to intercept HSV-1’s exploitation of host keratinocyte signaling. Methods: Human HaCaT keratinocytes were infected with HSV-1 and treated with U0126 or LY294002. Western blotting was used to assess phosphorylation of ERK1/2 and activation of protein kinase B (AKT). MTT assays were performed to evaluate cell viability. Real-time PCR was utilized to quantify viral transcripts (ICP0, ICP4, gB, and gC) and inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)]. Confocal microscopy was employed to visualize the intracellular distribution of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), phosphorylated activation of protein kinase B (p-AKT), and HSV-1 glycoprotein D (gD). Viral titers were determined using plaque assays. Results: The HSV-1 infection induced a time-dependent increase in phosphorylation of ERK1/2 and AKT, with p-ERK1/2 peaking at 12 h and p-AKT increasing 2.5-fold by 24 h. Cell viability declined from 100% at baseline to 45% at 24-hours post-infection (hpi). Treatment with U0126 and LY294002 reduced p-ERK1/2 and p-AKT levels to 25% and 30% of infected controls, respectively, restoring viability to 82 - 86%. Both inhibitors markedly suppressed viral gene expression (ICP0, ICP4, gB, gC down by 60 - 80%) and inflammatory cytokines (IL-6 and TNF-α reduced by > 50%). Plaque assays showed a strong decline in infectious titers — from 175 plaques per well in untreated infection to 60 and 45 plaques after U0126 and LY294002, respectively. Confocal imaging further revealed diminished nuclear accumulation of p-ERK1/2 and p-AKT, indicating disruption of post-entry signaling critical for viral replication. Conclusions: Targeting host signaling bottlenecks with U0126 and LY294002 offers a dual-pronged antiviral strategy against HSV-1 by dismantling the ERK/AKT axis critical for replication and inflammatory amplification. These findings position MEK1/2 and PI3K as promising therapeutic nodes for managing cutaneous HSV-1 infections. This host-directed dual-pathway inhibition may therefore help reduce recurrent orolabial HSV-1 lesions.

Role of environmental fungi and Aspergillus fumigatus in respiratory diseases remains evident; however, its contribution to directly influencing lung cancer progression remains obscure. In this study, we investigated the effect of Aspergillus fumigatus extract (AFE) on the development of tumor-promoting characteristics in human lung cancer cell lines. The organism was distinguished based on Lactophenol Cotton Blue staining and further distinguished with protein expression patterns via SDS-PAGE and BCA analysis. A549 and H1299 lung adenocarcinoma human cell lines were challenged with AFE, and various cellular responses were monitored simultaneously for cell viability, proliferative activity, inflammatory gene expression, DNA damage expression, and migratory responses. AFE caused increased cell viability and exhibited cellular characteristics of highly proliferating cells with significant expression of Cyclin D1 and c-MYC. Highly inflammatory gene expression responses and protein expressions of AKT, ERK1/2, and NF-κB signaling pathways were noticed at both the gene and protein expression levels with NF-κB nuclear translocation verified with confocal microscopy studies. DNA damage expression markers like γ-H2AX, p-ATM, and p53 significantly contributed with observable genomic DNA cleavage. Additionally, AFE-exposed cells exhibited faster wound closure and expression of Epithelial-mesenchymal transition-associated factors contributing to cell migration and therapeutic efficacy of this combined approach needs further investigation and development into a targeting therapeutic agent against lung cancer.