Plant Source Derived Compound Exhibited In Silico Inhibition of Membrane Glycoprotein In SARS-CoV-2: Paving the Way to Discover a New Class of Compound For Treatment of COVID-19.

SARS-CoV-2 is the virus responsible for causing COVID-19 disease in humans, creating the recent pandemic across the world, where lower production of Type I Interferon (IFN-I) is associated with the deadly form of the disease. Membrane protein or SARS-CoV-2 M proteins are known to be the major reason behind the lower production of human IFN-I by suppressing the expression of IFNß and Interferon Stimulated Genes. In this study, 7,832 compounds from 32 medicinal plants of India possessing traditional knowledge linkage with pneumonia-like disease treatment, were screened against the Homology-Modelled structure of SARS-CoV-2 M protein with the objective of identifying some active phytochemicals as inhibitors. The entire study was carried out using different modules of Schrodinger Suite 2020-3. During the docking of the phytochemicals against the SARS-CoV-2 M protein, a compound, ZIN1722 from Zingiber officinale showed the best binding affinity with the receptor with a Glide Docking Score of -5.752 and Glide gscore of -5.789. In order to study the binding stability, the complex between the SARS-CoV-2 M protein and ZIN1722 was subjected to 50 ns Molecular Dynamics simulation using Desmond module of Schrodinger suite 2020-3, during which the receptor-ligand complex showed substantial stability after 32 ns of MD Simulation. The molecule ZIN1722 also showed promising results during ADME-Tox analysis performed using Swiss ADME and pkCSM. With all the findings of this extensive computational study, the compound ZIN1722 is proposed as a potential inhibitor to the SARS-CoV-2 M protein, which may subsequently prevent the immunosuppression mechanism in the human body during the SARS-CoV-2 virus infection. Further studies based on this work would pave the way towards the identification of an effective therapeutic regime for the treatment and management of SARS-CoV-2 infection in a precise and sustainable manner.

The Interplay of the Unfolded Protein Response in Neurodegenerative Diseases: A Therapeutic Role of Curcumin.

Abnormal accumulation of misfolded proteins in the endoplasmic reticulum and their aggregation causes inflammation and endoplasmic reticulum stress. This promotes accumulation of toxic proteins in the body tissues especially brain leading to manifestation of neurodegenerative diseases. The studies suggest that deregulation of proteostasis, particularly aberrant unfolded protein response (UPR) signaling, may be a common morbific process in the development of neurodegeneration. Curcumin, the mixture of low molecular weight polyphenolic compounds from turmeric, Curcuma longa has shown promising response to prevents many diseases including current global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurodegenerative disorders. The UPR which correlates positively with neurodegenerative disorders were found affected by curcumin. In this review, we examine the evidence from many model systems illustrating how curcumin interacts with UPR and slows down the development of various neurodegenerative disorders (ND), e.g., Alzheimer's and Parkinson's diseases. The recent global increase in ND patients indicates that researchers and practitioners will need to develop a new pharmacological drug or treatment to manage and cure these neurodegenerative diseases.