Activation of inflammasome by SARS-CoV-2 and the role of this platform in the pathogenesis of COVID-19: a prospective study aimed at inhibiting NLRP3 for the treatment of COVID-19

  • Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP)
  • Total publications:5 publications

Grant number: 2020/04964-8

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2022
  • Known Financial Commitments (USD)

    $65,976.93
  • Funder

    Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP)
  • Principle Investigator

    Pending
  • Research Location

    Brazil, Americas
  • Lead Research Institution

    Universidade de São Paulo
  • Research Category

    Pathogen: natural history, transmission and diagnostics

  • Research Subcategory

    Immunity

  • Special Interest Tags

    Gender

  • Study Subject

    Clinical

  • Clinical Trial Details

    Not applicable

  • Broad Policy Alignment

    Pending

  • Age Group

    Unspecified

  • Vulnerable Population

    Unspecified

  • Occupations of Interest

    Unspecified

Abstract

COVID-19, caused by the new coronavirus (SARS-CoV-2) has become a worldwide health problem, with more than one million confirmed cases and 50,000 deaths by the beginning of April 2020. In its most severe forms, COVID-19 manifests itself in the form of fever, cough, fatigue, dyspnoea, headache and may progress to respiratory distress syndrome and death. The most severe cases are characterized by an intense inflammatory process, with important recruitment of classically activated neutrophils and macrophages. There are also high concentrations of inflammatory cytokines, such as IL-6 and IL-1², which is produced in a manner dependent on the inflammasome, a complex of intracellular proteins that promotes inflammatory processes. The presence of high concentrations of IL-1² in patients suggests an important participation of the inflammasome in the pathogenesis of COVID-19. Thus, we intend to evaluate the inflammasome activation in response to SARS-CoV-2 infection in cell cultures and in clinical material obtained from patients with COVID-19. We also intend to monitor inflammasoma activation in a prospective study with 60 patients hospitalized for SARS-CoV-2 at HC-FMRP who will be treated with chloroquine in combination (or not) with colchicine, a drug widely used for the treatment of mediated diseases by NLRP3 inflammasome, as a gout. Colchicine prevents the formation of tubulin dimers, inhibiting several cellular processes, including the activation of the inflammasoma. Thus, the development of this research project should directly contribute to the understanding of the pathophysiology of COVID-19, in addition to providing a mechanistic basis for the use of colchicine as a possible treatment for patients with COVID-19.

Publicationslinked via Europe PMC

Last Updated:37 minutes ago

View all publications at Europe PMC

Inflammasome activation by SARS-CoV-2 and its participation in COVID-19 exacerbation.

CASP4/11 Contributes to NLRP3 Activation and COVID-19 Exacerbation.

Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients.

Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial.