COVID-19 is announced as a global pandemic in 2020. Its mortality and morbidity rate are rapidly increasing, with limited medications. The emergent outbreak of COVID-19 prompted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps spreading. In this infection, a patient's immune response plays pivotal role in the pathogenesis. This inflammatory factor was shown by its mediators that, in severe cases, reach the cytokine at peaks. Hyperinflammatory state may sparks significant imbalances in transporters and drug metabolic machinery, and subsequent alteration of drug pharmacokinetics may result in unexpected therapeutic response. The present scenario has accounted for the requirement for therapeutic opportunities to relive and overcome this pandemic. Despite the diminishing developments of COVID-19, there is no drug still approved to have significant effects with no side effect on the treatment for COVID-19 patients. Based on the evidence, many antiviral and anti-inflammatory drugs have been authorized by the Food and Drug Administration (FDA) to treat the COVID-19 patients even though not knowing the possible drug-drug interactions (DDI). Remdesivir, favipiravir, and molnupiravir are deemed the most hopeful antiviral agents by improving infected patient’s health. Dexamethasone is the first known steroid medicine that saved the lives of seriously ill patients. Some oligopeptides and proteins have also been using. The current review summarizes medication updates to treat COVID-19 patients in an inflammatory state and their interaction with drug transporters and drug-metabolizing enzymes. It gives an opinion on the potential DDI that may permit the individualization of these drugs, thereby enhancing the safety and efficacy.

MYC amplification or overexpression is most common in Group 3 medulloblastomas and is positively associated with poor clinical outcomes. Recently, protein arginine methyltransferase 5 (PRMT5) overexpression has been shown to be associated with tumorigenic MYC functions in cancers, particularly in brain cancers such as glioblastoma and medulloblastoma. PRMT5 regulates oncogenes, including MYC, that are often deregulated in medulloblastomas. However, the role of PRMT5-mediated post-translational modification in the stabilization of these oncoproteins remains poorly understood. The potential impact of PRMT5 inhibition on MYC makes it an attractive target in various cancers. PRMT5 inhibitors are a promising class of anti-cancer drugs demonstrating preclinical and preliminary clinical efficacies. Here, we review the publicly available preclinical and clinical studies on PRMT5 targeting using small molecule inhibitors and discuss the prospects of using them in medulloblastoma therapy.

This study was evaluated synergistic effect of a polyherbal formulation (PHF) of Allium sativum L., Eugenia jambolana Lam., Momordica charantia L., Ocimum sanctum Linn., and Psidium guajava L. on p-glycoprotein (Pgp) of intestine. These five herbs were traditionally used for diabetes. These herbs are commonly present in Ayurvedic product as antidiabetics in India. PHF was prepared by five indigenous herbs. Different doses (50, 100 and 200 mg/kg/day) of were orally administered to Sprague-Dawley rats of different groups for multiple weeks except control groups. Alteration in Pgp expression was evaluated by real-time-polymerase chain reaction and western blotting while modulation in activity of Pgp was evaluated using rhodamine 123 (Rh123) as transport substrate by in-situ absorption and everted gut sac method. In PHF, pretreated group received 50, 100 and 200 mg/kg/day for 7 days, mRNA level decreased by 1.75, 2.45 and 2.37-fold, respectively, as compared to control. Similarly, when PHF at dose of 100 mg/kg/day was given consequently for 4 weeks, maximum decrease in Pgp expression level was observed only after 1 week and further increase in the treatment duration did not produce significant decrease compared to the 1^st week treatment. Pgp mediated transport of Rh123 was significantly decreased with everted gut sac prepared from PHF pretreated rats (1 week) compared to those prepared from vehicle treated rats. We report that PHF pretreatment downregulated the expression of intestinal Pgp and this downregulated intestinal Pgp would result in decreased functional activity. In addition, this downregulated Pgp expression might affect the bioavailability of antidiabetic Pgp substrate drugs.