Literature review on virus and host response proteins in COVID-19: pathobiology, management, diagnosis and treatment.

Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by a novel strain of coronavirus (SARS-CoV-2) which was declared by WHO as a cause of global pandemic. By human-to-human transmission it caused severe damage to mankind with increased mortality rate worldwide. Coronavirus is a spherical enveloped virus with single stranded positive-sense RNA with a size of ~30 kilobases encoding various structural, non-structural and accessory proteins. The entry of coronavirus into the host cells is mediated by spike proteins. SARS-CoV-2 efficiently replicates in host cell and by evading immune surveillance, like innate and adaptive immune responses, in the host cells ultimately leads to increased virulence and disease outcome. In the current review, we highlighted the molecular insights of SARS-CoV-2 and its infection mechanism in the host cell via host-viral protein interactions based on currently available data up to 16thMay 2020 using various research literature databases. The diagnostics of SARS-CoV-2 is mainly done by RT-qPCR and serological tests. There is no effective treatment for COVID-19, however, few methods like plasma therapy and remdesivir treatment are reported to show promising results in improving patient's health and decreasing mortality rate. Keywords: SARS-CoV; spike protein; nucleocapsid; COVID-19; interferon.

Radiation-induced H3K9 tri-methylation in E-cadherin promoter during lung EMT: in vitro and in vivo approaches using vanillin.

Radiotherapy is an important treatment regime for lung cancer, worldwide. However, radiation-induced pneumonitis and fibrosis are the treatment-limiting toxicities among patients who have undergone radiotherapy. The epithelial cells via epithelial to mesenchymal transition [EMT] acquires mesenchymal phenotype, which ultimately leads to fibrosis. Many investigations are focussed on understanding the signalling pathways mediating in EMT, however, the role of histone methylation is less understood in radiation-induced lung EMT. In the present study, we analysed the effect of vanillin, an antioxidant, on histone methylation during radiation-induced EMT. The thoracic region of Wistar rats was irradiated with a fractionated dose of X-ray (3 Gy/day) for two weeks (total of 30 Gy). The irradiated animals were sacrificed at the 8th and 16th weeks and tissues were used for analyses. Our data showed that radiation decreased the level of antioxidant enzymes such as SOD, catalase and reduced glutathione that would ultimately enhance oxidative stress in the tissues. Histopathological analysis revealed that radiation increased the infiltration of inflammatory cells to the tissue injury site. Total global histone methylation was increased upon irradiation, which was effectively prevented by vanillin administration. Vanillin enhanced E-cadherin expression and decreased the mesenchymal markers N-cadherin and vimentin in the irradiated lung tissue. The ChIP-qPCR analysis suggested that snail expression in the nucleus might involve in the enrichment of suppressive marker H3K9me3 on the E-cadherin promoter. Finally, we suggested that vanillin administration decreased radiation-induced oxidative stress and EMT expression. Additionally, irradiation increased the H3K9 methylation status with nuclear translocation of snail during lung EMT.

The epigenetics of brain tumors and its modulation during radiation: A review.

The brain tumor is the abnormal growth of heterogeneous cells around the central nervous system and spinal cord. Most clinically prominent brain tumors affecting both adult and pediatric are glioblastoma, medulloblastoma, and ependymoma and they are classified according to their origin of tissue. Chemotherapy, radiotherapy, and surgery are important treatments available to date. However, these treatments fail due to multiple reasons, including chemoresistance and radiation resistance of cancer cells. Thus, there is a need of new therapeutic designs to target cell signaling and molecular events which are responsible for this resistance. Recently epigenetic changes received increased attention because it helps in understanding chromatin-mediated disease mechanism. The epigenetic modification alters chromatin structure that affects the docking site of many drugs which cause chemo-resistance of cancer therapy. This review centers the mechanism of how epigenetic changes affect the transcription repression and activation of various genes including Polycomb gene, V-Myc avian myelocytomatosis viral oncogene (MYCN). This review also put forth the pathway of radiation-induced reactive oxygen species generation and its role in epigenetic changes in the cellular level and its impact on tissue physiology. Additionally, there is a strong relationship between the behavior of an individual and environment-induced epigenetic regulation of gene expression. The review also discusses Transcriptome heterogeneity and role of tumor microenvironment in glioblastoma. Overall, this review emphasis important and novel epigenetic targets that could be of therapeutic benefit, which helps in overcoming the unsolved chromatin alteration in brain cancer.