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HGNC Genes

SARS-CoV-2 proteins

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    Pan- ErbB HGNC inhibition protects from SARS-CoV-2 replication, inflammation MESHD, and injury

    Authors: Sirle Saul; Marwah Karim; Pei Tzu Huang; Luca Ghita; Winston Chiu; Sathish Kumar; Nishank Bhalla; Pieter Leyssen; Courtney A. Cohen; Kathleen E. Huie; Courtney Tindle; Malaya Kumar Sahoo; Mamdouh Sibai; Benjamin A. Pinsky; Soumita Das; Pradipta Ghosh; John Dye; David E. Solow-Cordero; Jing Jin; Dirk Jochmans; Johan Neyts; Aarthi Narayanan; Steven De Jonghe; Shirit Einav

    doi:10.1101/2021.05.15.444128 Date: 2021-05-16 Source: bioRxiv

    Effective therapies are needed to combat emerging viruses. Seventeen candidates that rescue cells from SARS-CoV-2-induced lethality and target diverse functions emerged in a screen of 4,413 compounds. Among the hits was lapatinib, an approved inhibitor of the ErbB HGNC family of receptor tyrosine kinases. Lapatinib and other pan- ErbB HGNC inhibitors suppress replication of SARS-CoV-2 and unrelated viruses with a high barrier to resistance. ErbB4, but not lapatinib's cancer MESHD targets ErbB1 and ErbB2, is required for SARS-CoV-2 entry MESHD and Venezuelan equine encephalitis virus infection MESHD and is a molecular target mediating lapatinib's antiviral effect. In human lung organoids, lapatinib protects from SARS-CoV-2-induced activation of pathways implicated in acute and chronic lung injury MESHD downstream of ErbBs ( p38 HGNC-MAPK, MEK HGNC/ ERK HGNC, and AKT HGNC/ mTOR HGNC), pro-inflammatory cytokine production, and epithelial barrier injury MESHD. These findings reveal regulation of viral infection MESHD, inflammation MESHD, and tissue injury via ErbBs MESHD and propose approved candidates to counteract these effects with implications for coronaviruses and unrelated viruses.

    Exaggerated cytokine production in human peripheral blood mononuclear cells by recombinant SARS-CoV-2 spike PROTEIN glycoprotein S1 and its inhibition by dexamethasone

    Authors: Olumayokun A Olajide; Victoria U Iwuanyanwu; Izabela Lepiarz-Raba; Alaa A Al-Hindawi

    doi:10.1101/2021.02.03.429536 Date: 2021-02-03 Source: bioRxiv

    An understanding of the pathological inflammatory mechanisms involved in SARS CoV-2 virus infection MESHD is necessary in order to discover new molecular pharmacological targets for SARS-CoV-2 spike PROTEIN glycoprotein. In this study, the effects of a recombinant SARS CoV-2 spike PROTEIN glycoprotein S1 was investigated in human peripheral blood mononuclear cells (PBMCs). Stimulation with spike glycoprotein S1 PROTEIN (100 ng/mL) resulted in significant elevation in the production of TNF HGNC, IL-6 HGNC, IL-1{beta HGNC} and IL-8 HGNC. However, pre-treatment with dexamethasone (100 nM) caused a significant reduction in the release of these cytokines. Further experiments revealed that S1 stimulation of PBMCs increased phosphorylation of NF-{kappa}B HGNC p65 HGNC and I{kappa}B, while increasing I{kappa}B degradation. DNA binding of NF-{kappa}B HGNC p65 HGNC was also significantly increased following stimulation with S1. Treatment of PBMCs with dexamethasone (100 nM) or BAY11-7082 (1 M) resulted in inhibition of S1-induced NF-{kappa}B HGNC activation. Activation of p38 HGNC MAPK by S1 was blocked in the presence of dexamethasone and SKF 86002. CRID3, but not dexamethasone pre-treatment produced significant inhibition of S1-induced activation of NLRP3 HGNC/ caspase 1 HGNC. Further experiments revealed that S1-induced increase in the production of TNF HGNC, IL-6 HGNC, IL-1{beta HGNC} and IL-8 HGNC was reduced in the presence of BAY11-7082 and SKF 86002, while CRID3 pre-treatment resulted in the reduction of IL-1{beta HGNC} production. These results suggest that SARS-CoV-2 spike PROTEIN glycoprotein S1 stimulate PBMCs to release pro inflammatory cytokines through mechanisms involving activation of NF-{kappa}B HGNC, p38 MAPK and NLRP3 HGNC inflammasome. It is proposed that clinical benefits of dexamethasone in COVID-19 MESHD is possibly due to its anti-inflammatory activity in reducing SARS-CoV-2 cytokine storm.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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