Complement System Inhibitory Drugs in a Zebrafish (Danio rerio) Model: Computational Modeling

Autor(es)

Fernandes, Dayanne Carla ; Tambourgi, Denise V.

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 18, p. 20-pg., 2023-09-01.

Resumo

The dysregulation of complement system activation usually results in acute or chronic inflammation and can contribute to the development of various diseases. Although the activation of complement pathways is essential for innate defense, exacerbated activity of this system may be harmful to the host. Thus, drugs with the potential to inhibit the activation of the complement system may be important tools in therapy for diseases associated with complement system activation. The synthetic peptides Cp40 and PMX205 can be highlighted in this regard, given that they selectively inhibit the C3 and block the C5a receptor (C5aR1), respectively. The zebrafish (Danio rerio) is a robust model for studying the complement system. The aim of the present study was to use in silico computational modeling to investigate the hypothesis that these complement system inhibitor peptides interact with their target molecules in zebrafish, for subsequent in vivo validation. For this, we analyzed molecular docking interactions between peptides and target molecules. Our study demonstrated that Cp40 and the cyclic peptide PMX205 have positive interactions with their respective zebrafish targets, thus suggesting that zebrafish can be used as an animal model for therapeutic studies on these inhibitors. (AU)

• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 19/27348-3 - Inibição do sistema complemento como meio para controlar a inflamação associada a envenenamentos
• Beneficiário: Dayanne Carla Fernandes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado