Bioprospecting of Meliaceae family phytomolecules for the treatment of monkeypox virus infection: a QSAR modeling and MD simulation approach.

Recent monkeypox virus (MPXV) infections show the risk of MPXV transmission that persists today and the significance of surveillance and quick response methods to stop the virus's spread. Currently, the monkeypox virus infection is not specifically treated. In this study, QSAR models were designed using known inhibitors of cysteine proteinase from the vaccinia virus, where the Random Forest model and Ridge model had showed the best correlation between predicted and observed EC50. These models were used to screen Maliaceae family phytochemicals against MPXV cysteine proteinase. The compound, IMPHY010637 was detected in top 5 from both the QSAR screening models and showed best docked score (-8.6 kcal/mol) and thus selected for further investigation. Further, the IMPHY010637 showed interaction with the catalytic residue His241 of the protein as reported in earlier studies. The ADMET analysis of the compound showed the acceptable drug-like properties of IMPHY010637. However, these properties could be improved after experimental validation of protein-ligand binding. Both docked complex and poses created in 100 ns MD simulation of the protein-ligand complex showed the presence of multiple hydrogen bonds. RMSD and conformation analysis showed stable binding of IMPHY010637 with the cysteine proteinase of MPXV at its active site. Compared to the known inhibitor, IMPHY010637 showed better binding with the protein as observed by the PCA and MM/GBSA analysis. This study concluded IMPHY010637 as a potential inhibitor for the cysteine proteinase of MPXV using computational methods that could be tested in in-vitro experiments.Communicated by Ramaswamy H. Sarma.

Early Development of Cancer Treatments.

The treatment of cancer has evolved as our understanding of the underlying biological processes has improved. Yet, the efficient delivery of cancer therapeutics remains a major challenge in the filed necessitating a multidisciplinary approach that integrates knowledge obtained from diverse fields, such as chemistry, biology, engineering, and medicine. Cancer treatment aims to remove all or most of the tumor as possible and to prevent the recurrence or spread of the primary tumor. Cancer treatment involves a careful examination of the available options, which may include a combination of the major treatment methods, such as surgery with chemotherapy and/or radiation therapy. The type of therapy chosen depends on several factors, such as the location, grade, and stage of the tumor, as well as the patient's performance status. As new knowledge about cancer biology becomes available, treatments will be developed and modified in the pursuit of cancer cures to improve efficacy, precision, survivability, and quality of life. The main objective of this review is to expand our understanding of the early development of commonly applied cancer treatment strategies: surgery, chemotherapy, and radiotherapy. Keywords: Chemotherapy; Radiotherapy; Surgery; Therapy; Tumor.

Phenolic-Compound-Rich Opuntia littoralis Ethyl Acetate Extract Relaxes Arthritic Symptoms in Collagen-Induced Mice Model via Bone Morphogenic Markers.

Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation and progressive joint dysfunction. Opuntia littoralis (OL) has a high nutritional content and is thought to offer a number of health advantages. We aimed to evaluate the anti-arthritic potential of OL extracts against collagen-induced arthritis (CIA). We designed three OL cladode fractions from the concentrated aqueous extract: hexane, ethyl acetate (EAE), and hydro alcohol (HAE). We investigated the nitric oxide and MDA levels of EAE against lipopolysaccharide-induced RAW264.7 cells; then, we administered EAE to the mice with CIA to confirm the anti-inflammatory effects against RA. HPLC analysis of the OL extracts showed a high concentration of phenolic compounds in EAE. Treatment with EAE (10 and 20 mg/100 g body weight of mice) after 10 days of immunization with collagen showed a significant inhibition of joint inflammation, paw swelling, and edemas. MDA and cytokine levels (IL-1ß, IL-6R, IL-6, IL-17, and IL-23) were significantly reduced. EAE effectively ameliorated COX-2, NF-kB, STAT-3, PTEN, and RANKL expression. OL-EAE therapy significantly upregulated the expression of miR-28 and miR-199a. In conclusion, the anti-inflammatory actions of OL-EAE altered the cellular localization of the inflammatory mediators, therefore preventing joint inflammation via partial epigenetic and metabolic regulations in experimental mice.