The tumour suppressor protein PTEN is often down-regulated in non-small cell lung cancer. A major protein promoting the lowering of the PTEN protein is WWP2. Polyphenols have been shown to promote the expression of tumour suppressor genes like PTEN. We carry out the study to check for the ability of apigenin to bind with the WWP2 protein using in-silico investigation comprising docking and simulation. We checked for the cytotoxic effect of apigenin upon the non-small cell lung cancer cell line NCI-H23. We checked the PTEN expression status at the gene and protein levels. The expression levels of the apoptotic regulators BCL2, BAX and CASPASE3 genes along with the activity levels of the caspase-3 protein were checked. The ultrastructure of the cells was analysed. Our Autodock analysis showed that apigenin bound favourably with the WWP2 protein. Molecular dynamics simulation revealed that apigenin increased the parameters of RMSD, Rg and SASA when bound with the WWP2 protein. The protein-ligand complex had hydrogen bonding and majorly van der Wal's interactions. PCA analysis revealed greater fluctuations in the apigenin-bound state of the protein. The mutant form of the WWP2 revealed similar results in the presence of apigenin. Apigenin showed efficacy against the NCI-H23 cell line and promoted PTEN protein levels, lowered BCL2 gene expression and up-regulated BAX and CASPASE3 gene expression. Increased caspase-3 activity and ultra-structural analysis revealed the occurrence of apoptosis. Thus the binding of apigenin with WWP2 could promote PTEN protein levels and lead to apoptotic activity in NCI-H23 cells. [GRAPHICS]

Flavivirus infections are common in several parts of the world. Two major types of flaviviruses are dengue and zika viruses. Both these two viral infections have caused many fatalities around the world. There is an absence of a vaccine and an effective medication against these viruses. In this study, we analyzed the ability of dronabinol to act as a potential cure against these viral infections. We performed the docking of dronabinol with several viral proteins followed by molecular dynamics simulation, MM/PBSA and PCA analysis. We checked the ability of the polyphenol dronabinol to interfere with the binding of viral helicases to their cellular targets. We performed 2 D-QSAR studies, drug likeliness, ADMET and target prediction studies. From our study, we observed that dronabinol had the best docking ability against the helicase proteins of dengue and zika. Molecular dynamics simulation and MM/PBSA investigation confirmed the stability of the binding while PCA investigation showed a lowering of molecular motions in response to dronabinol docking to the helicases. Dronabinol interfered in the binding of the helicases to RNA. 2 D QSAR studies revealed a low IC₅₀ value for dronabinol. Dronabinol showed favorable drug-likeness, ADMET properties and target prediction results. Thus we propose dronabinol be further investigated in-vitro as a cure against dengue and zika virus infections. Communicated by Ramaswamy H. Sarma

Cancer is a disease that can be caused by infectious agents like bacteria, parasites, and viruses. Viral infections can be attributed to over 17% of cancer cases recorded across the world. This chapter offers an examination of the historical, current, and potential future trajectories of emerging oncogenic viral infections, with a focus on notable viruses including human papillomavirus (HPV), Epstein–Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-cell lymphotropic virus type 1 (HTLV-1). Oncogenic viruses can cause mutations in critical genes and/or alter several pathways that regulate the hallmarks of cancers like genomic stability, suppression of apoptosis, and modulation of immune system. The traditional therapeutic modalities for oncogenic viral infections include vaccination, radiotherapy, targeted therapy, and immune-oncotherapy. Newer emerging virus variants have been under study for their potential to promote cancers in the infected host cells. The interplay between viral infections and host immune responses highlights the need for immunotherapeutic approaches in managing virus-associated cancers. Several new vaccines, targeted drugs against viral proteins, and polyphenols against viral proteins are being currently investigated as potential answers against oncogenic viral infections. <!----> <!----> <!----> <!---->

Inhibition of enzymes has been a major drug target for curing diseases. Xanthine oxidase is involved in the production of uric acid. The enzyme has elevated levels of activity in various diseases like gout, cardiovascular diseases etc. Tyrosinase is a melanin producing enzyme. Increased levels of tyrosinase activity has been observed in a number of diseases like skin pigmentation disorders, melanoma tumors etc. Several investigations have not yielded inhibitors of these enzymes that have minimal side effects. Cuminaldehyde is a natural aldehyde which has been reported to be bioactive. The in-vitro enzyme activity assays for the enzymes xanthine oxidase and tyrosinase were done in absence and presence of cuminaldehyde. We docked cuminaldehyde against xanthine oxidase and tyrosinase proteins using Autodock 4.0 followed by molecular dynamics simulation. In-vitro enzyme activity assays showed that cuminaldehyde caused a better reduction of tyrosinase activity as compared to xanthine oxidase activity. Autodock analysis showed that cuminaldehyde bound favourably with both xanthine oxidase and tyrosinase. The simulation studies revealed that the tyrosinase protein took up an extended conformation when bound to cuminaldehyde and stable binding occurred between them. Cuminaldehyde cleared multiple drug filters and showed favourable ADMET properties. As such, cuminaldehyde can be further researched upon to validate its potential as an inhibitor of the tyrosinase protein. Graphical abstract