Targeting Viral ORF3a Protein: A New Approach to Mitigate COVID-19 Induced Immune Cell Apoptosis and Associated Respiratory Complications.

Infection with SARS-CoV-2 is a growing concern to the global well-being of the public at present. Different amino acid mutations alter the biological and epidemiological characteristics, as well as immune resistance of SARS-CoV-2. The virus-induced pulmonary impairment and inflammatory cytokine storm are directly related to its clinical manifestations. But, the fundamental mechanisms of inflammatory responses are found to be the reason for the death of immune cells which render the host immune system failure. Apoptosis of immune cells is one of the most common forms of programmed cell death induced by the virus for its survival and virulence property. ORF3a, a SARS-CoV-2 accessory viral protein, induces apoptosis in host cells and suppress the defense mechanism. This suggests, inhibiting SARS-CoV-2 ORF3a protein is a good therapeutic strategy for the treatment in COVID-19 infection by promoting the host immune defense mechanism.

Apoptosis promoting activity of selected plant steroid in MRMT-1 breast cancer cell line by modulating mitochondrial permeation pathway.

Escape from apoptosis is one of the main demeanor characteristics of cancer cells. Mitochondria are key players in initiating and regulating the intrinsic apoptosis pathway. Hexokinase2 (HK2) is ubiquitously expressed in several cancer cells and is essential for cell survival and death. The binding of HK2 to mitochondria promotes cell proliferation, while AKT-1 mediated pathway is crucial in this process. Peimine, a steroidal alkaloid derived from plant steroids, is screened for docking properties, ADMET properties, and drug-likeness. Apoptosis targets are predicted by network pharmacology using 47 genes associated with apoptosis. According to in silico study, peimine has the potential for dual Targeting on HK2 and AKT1. For further confirmation, peimine was subjected to Cell culture studies using MRMT-1 rat breast cancer cells. The elevated levels of cytochrome c and Caspase 9 activity indicate that the intrinsic apoptosis pathway causes cell death. The decreased glucose uptake by the MRMT-1 cells indicates that pimine inhibits glucose transport by inhibiting the membrane HK2.