I have found some info Regarding other proteins which interact with the viral E Protein and its potential as a target. What relevance it has to BIT i'm not sure. Will BIT drug BIT036 or when they announce they have one against COVID-19 take out E and other proteins attached because there are signalling pathways that keep viral replication alive. Plus there are other non structural Proteins that are for replication as well like Nsp3,4,6 as shown in table below., not sure how they get taken out. .
https://virologyj.biomedcentral.com/articles/10.1186/s12985-019-1182-0Coronavirus envelope protein: current knowledge
It is particularly noteworthy that SARS-CoV encodes two accessory proteins, 3a and 8a, that might exhibit relative compensatory functions in the absence of E [285, 286]. In terms of viral replication in vivo and in vitro, 3a could partially compensate for the loss of E. Moreover, 3a also contains a PBM and might be able to compensate for the loss of E to an extent but utilises different signalling pathways [285]. Although the study demonstrated that even the accessory proteins demonstrate some measure of dispensability, the virus still encodes these additional proteins with overlapping functions. The dynamics between these proteins, however, are not quite clear yet and warrants further investigation.https://towardsdatascience.com/covid-19-and-drug-development-b800d8917b50A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug Repurposinghttps://www.biorxiv.org/content/10.1101/2020.03.22.002386v3.full.pdfSARS-CoV-2 envelope interacts with bromodomain proteinsSurprisingly, we find that the transmembrane protein E binds to the bromodomain-containing proteins BRD2 and
BRD4 (Fig. 4d, Extended Data Fig. 9), potentially disrupting BRD-histone binding by mimicking histone structure.
BRD2 is a member of the bromodomain and extra-terminal (BET) domain family whose members bind acetylated
histones to regulate gene transcription 69. The N-terminus of histone 2A shares local sequence similarity over an
alpha-helix of approximately 15 residues, some of which are in a transmembrane segment, of Protein E (Fig.
4d). Moreover, this matching region of the histone is spanned by acetylated lysine residues shown to bind
BRD270. This analysis may suggest that Protein E mimics the histone to disrupt its interaction with BRD2, thus
inducing changes in host's protein expression that are beneficial to the virus.
For a more comprehensive overview of the virus-host interactions we detected, see Supplemental Discussion.
Identification of existing drugs targeting SARS-CoV-2 human host factors."Similarly, drugs exist to target several well-known epigenetic
regulators prominent among the human interactors, including HDAC2, BRD2 and BRD4, which interact with viral
proteins nsp5 and E, respectively (Figs. 3 and 5a). The approved drug Valproic acid (an anticonvulsant) and the
pre-clinical candidate Apicidin inhibit HDAC2 with affinities of 62 μM and 120 nM, respectively. Clinical
compounds ABBV-744 and CPI-0610 act on BRD2/4, with an affinity of 2 nM or 39 nM, respectively -- several
preclinical compounds also target bromodomain-containing proteins (Table 1a,b)."
https://www.caymanchem.com/news/uncovering-the-role-of-brd2-in-covid-19
BRD2, a member of the bromodomain extra terminal protein family, is known to regulate the expression of 1,450 genes. It is specifically localized at promoters of target genes, and early reports from the cell mapping initiative at Quantitative Biosciences Institute Coronavirus Research Group indicate that BRD2 interacts with SARS-CoV-2 envelope proteins. It is not yet known why the virus needs BRD2https://www.nytimes.com/2020/03/17/science/coronavirus-treatment.htmlProtein Targets
Scientists have mapped hundreds of the proteins in human cells that the coronavirus uses to grow. Their goal is to find an antiviral drug that can prevent the virus from replicating.
The flu like symptoms observed in infected people are the result of the coronavirus attacking cells in the respiratory tract. The new map shows that the virus’s proteins travel throughout the human cell, engaging even with proteins that do not seem to have anything to do with making new viruses.
One of the viral proteins, for example, latches onto BRD2, a human protein that tends to our DNA, switching genes on and off. Experts on proteins are now using the map to figure out why the coronavirus needs these molecules.
Dr. Shokat and his colleagues have found 50 promising candidates. The protein BRD2, for example, can be targeted by a drug called JQ1. Researchers originally discovered JQ1 as a potential treatment for several types of cancer.
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