Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinE (1)

ProteinS (1)


Filter

Genes
Diseases
SARS-CoV-2 Proteins
    displaying 1 - 2 records in total 2
    records per page




    Blockade of SARS-CoV-2 infection MESHD in-vitro by highly potent PI3K-α/ mTOR HGNC/ BRD4 HGNC inhibitor

    Authors: Arpan Acharya; Kabita Pandey; Michellie Thurman; Kishore B Challagundla; Kendra R Vann; Tatiana G Kutateladze; Guillermo A Morales; Donald L Durden; Siddappa N Byrareddy

    doi:10.1101/2021.03.02.433604 Date: 2021-03-03 Source: bioRxiv

    Pathogenic viruses like SARS-CoV-2 and HIV hijack the host MESHD molecular machinery to establish infection and survival in infected cells. This has led the scientific community to explore the molecular mechanisms by which SARS-CoV-2 infects MESHD host cells, establishes productive infection, and causes life-threatening pathophysiology. Very few targeted therapeutics for COVID-19 MESHD currently exist, such as remdesivir. Recently, a proteomic approach explored the interactions of 26 of 29 SARS-CoV-2 proteins with cellular targets in human cells and identified 67 interactions as potential targets for drug development. Two of the critical targets, the bromodomain and extra-terminal domain proteins (BETs): BRD2 HGNC/ BRD4 HGNC and mTOR HGNC, are inhibited by the dual inhibitory small molecule SF2523 at nanomolar potency. SF2523 is the only known mTOR HGNC PI3K-/( BRD2 HGNC/ BRD4 HGNC) inhibitor with potential to block two orthogonal pathways necessary for SARS-CoV-2 pathogenesis in human cells. Our results demonstrate that SF2523 effectively blocks SARS-CoV-2 replication in lung bronchial epithelial cells in vitro, showing an IC50 value of 1.5 {micro}M, comparable to IC50 value of remdesivir (1.1 {micro}M). Further, we demonstrated that the combination of doses of SF2523 and remdesivir is highly synergistic: it allows for the reduction of doses of SF2523 and remdesivir by 25-fold and 4-fold, respectively, to achieve the same potency observed for a single inhibitor. Because SF2523 inhibits two SARS-CoV-2 driven pathogenesis mechanisms involving BRD2 HGNC/ BRD4 HGNC and mTOR HGNC signaling, our data suggest that SF2523 alone or in combination with remdesivir could be a novel and efficient therapeutic strategy to block SARS-CoV-2 infection MESHD and hence be beneficial in preventing severe COVID-19 MESHD disease evolution. One Sentence SummaryEvidence of in silico designed chemotype (SF2523) targeting PI3K-/ mTOR HGNC/ BRD4 HGNC inhibits SARS-CoV-2 infection MESHD and is highly synergistic with remdesivir.

    A proteomic model of SARS-COV2 infection by comparing the interactomes of BRD4 HGNC with BET HGNC-inhibition and SARS-COV2 viral proteins – implications for re-purposing approved drugs or ubiquitin-mediated degradation of select candidates

    Authors: GIRISH NALLUR

    doi:10.21203/rs.3.rs-24573/v1 Date: 2020-04-22 Source: ResearchSquare

    The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 MESHD respiratory disease MESHD, has infected 2,029,930 people worldwide and caused 136,320 deaths. Consequently, the hunt for drugs showing efficacy against this deadly disease, or vaccines for prevention, are being intensely investigated. Unfortunately, there is a scarcity of research data on the molecular mechanisms of SARS-CoV-2 infection MESHD for quickly finding effective therapies, or repurposing existing drugs approved by the US FDA. This report models existing knowledge of SARS-COV2 viral proteins and the cellular proteins they interact with by comparisons with BRD4 HGNC interacting proteins identified from B cells, with or without BET HGNC inhibition. The E protein PROTEIN of SARS-COV2 interacts with BRD4 HGNC, and the Spike (S) protein PROTEIN with CANX HGNC. Extensive similarities were observed with published cellular interactants of 13 SARS-COV2 proteins resulting in 47 BRD4 HGNC-interacting protein candidates, with or without BET HGNC inhibition. 61 cellular protein targets and 132 FDA approved drugs which use these proteins as targets are proposed, which can be investigated for efficacy against SARS-COV2 infections MESHD. The implications to SARS-COV2 disease MESHD diagnosis, therapy and vaccine creation are discussed.

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).
The web page can also be accessed via API.

Sources


Annotations

All
None
MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


Export subcorpus as...

This service is developed in the project nfdi4health task force covid-19 which is a part of nfdi4health.

nfdi4health is one of the funded consortia of the National Research Data Infrastructure programme of the DFG.