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The Dual Role of cGAS-STING Signaling in COVID-19: Implications for Therapy

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Autor(es):
di Flora, Daniele Castro ; Lara, Joao Paulo Zanardini ; Dionizio, Aline ; Buzalaf, Marilia Afonso Rabelo
Número total de Autores: 4
Tipo de documento: Artigo Científico
Fonte: CELLS; v. 14, n. 5, p. 11-pg., 2025-03-01.
Resumo

The progression of COVID-19 involves a sophisticated and intricate interplay between the SARS-CoV-2 virus and the host's immune response. The immune system employs both innate and adaptive mechanisms to combat infection. Innate immunity initiates the release of interferons (IFNs) and pro-inflammatory cytokines, while the adaptive immune response involves CD4+ Th lymphocytes, B lymphocytes, and CD8+ Tc cells. Pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPS) and damage-associated molecular patterns (DAMPs), activating the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, a crucial component of the innate immune response to SARS-CoV-2. This pathway fulfills a dual function during infection. In the early phase of infection, the virus can suppress cGAS-STING signaling to avoid immune detection. However, in the late stages, the activation of this pathway may trigger excessive inflammation and tissue damage, exacerbating disease severity. Modulating the cGAS-STING pathway, whether through agonists like dimeric amidobenzimidazole (diABZI) or inhibitors targeting viral proteins, such as 3CLpro, for example, offers a promising approach for personalized therapy to control the immune response and mitigate severe inflammation, ultimately improving clinical outcomes in patients with severe COVID-19. (AU)

Processo FAPESP: 19/26070-1 - Modulação da película adquirida do esmalte e do biofilme para o controle da perda mineral dentária: desvendando mecanismos e possibilitando terapias
Beneficiário:Marília Afonso Rabelo Buzalaf
Modalidade de apoio: Auxílio à Pesquisa - Temático