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SARS-CoV-2 proteins

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    SARS-CoV-2 spike PROTEIN protein induces inflammation MESHD via TLR2 HGNC-dependent activation of the NF-κB pathway

    Authors: Shahanshah Khan; Mahnoush S. Shafiei; Christopher Longoria; John Schoggins; Rashmin C. Savani; Hasan Zaki

    doi:10.1101/2021.03.16.435700 Date: 2021-03-17 Source: bioRxiv

    Pathogenesis of COVID-19 MESHD is associated with a hyperinflammatory response; however, the precise mechanism of SARS-CoV-2-induced inflammation MESHD is poorly understood. Here we investigated direct inflammatory functions of major structural proteins of SARS-CoV-2. We observed that spike (S) protein PROTEIN potently induces inflammatory cytokines and chemokines including IL-6 HGNC, IL-1b HGNC, TNFa HGNC, CXCL1 HGNC, CXCL2 HGNC, and CCL2 HGNC, but not IFNs in human and mouse macrophages. No such inflammatory response was observed in response to membrane (M), envelope (E), and neucleocapsid ( N) proteins PROTEIN. When stimulated with extracellular S protein PROTEIN, human lung epithelial cells A549 also produce inflammatory cytokines and chemokines. Interestingly, epithelial cells expressing S protein PROTEIN intracellularly are non-inflammatory, but elicit an inflammatory response in macrophages when co-cultured. Biochemical studies revealed that S protein PROTEIN triggers inflammation MESHD via activation of the NF-kB pathway in a MyD88 HGNC-dependent manner. Further, such an activation of the NF-kB pathway is abrogated in Tlr2 HGNC-deficient macrophages. Consistently, administration of S protein PROTEIN induces IL-6, TNF-a, and IL-1b in wild-type, but not Tlr2-deficient mice. Together these data reveal a mechanism for the cytokine storm during SARS-CoV-2 infection MESHD and suggest that TLR2 could be a potential therapeutic target for COVID-19 MESHD.

    Currently available intravenous immunoglobulin (Gamunex(C)-C and Flebogamma(C) DIF) contains antibodies reacting against SARS-CoV-2 antigens

    Authors: José-María Díez; Carolina Romero; Rodrigo Gajardo

    doi:10.1101/2020.04.07.029017 Date: 2020-04-10 Source: bioRxiv

    BackgroundThere is a critical need for effective therapies that are immediately available to control the spread of COVID-19 MESHD disease. In this study, we assessed currently marketed intravenous immunoglobulin (IVIG) products for antibodies against human common coronaviruses that may cross-react with the SARS-CoV-2 virus. MethodsGamunex(R)-C and Flebogamma(R) DIF (Grifols) IVIG were tested against several betacoronaviruses antigens using ELISA techniques: HCoV (undetermined antigen), HCoV-HKU1 ( N protein PROTEIN), SARS-CoV (culture lysate), MERS-CoV ( N protein PROTEIN; S1 protein PROTEIN/RBD; S protein PROTEIN), and SARS-CoV-2 ( S1 protein PROTEIN). ResultsBoth IVIG products showed consistent reactivity to components of the tested viruses. Positive cross-reactivity was seen in SARS-CoV, MERS-CoV, and SARS-CoV-2. For SARS-CoV-2, positive reactivity was observed at IVIG concentrations ranging from 100 g/mL with Gamunex-C to 1 mg/mL with Flebogamma 5% DIF HGNC. ConclusionGamunex-C and Flebogamma DIF HGNC IVIG contain antibodies reacting against SARS-CoV-2 antigens. These preparations may be useful for immediate treatment of COVID-19 MESHD disease.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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