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:6 publications
Grant number: 2020/04964-8
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Key facts
Disease
COVID-19Start & end year
20202022Known Financial Commitments (USD)
$65,976.93Funder
Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP)Principal Investigator
PendingResearch Location
BrazilLead Research Institution
Universidade de São PauloResearch Priority Alignment
N/A
Research Category
Pathogen: natural history, transmission and diagnostics
Research Subcategory
Immunity
Special Interest Tags
N/A
Study Type
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.
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