Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PLpro Protein

Autor(es)

Bitencourt, Natalia Vitoria ; Righetto, Gabriela Marinho ; Camargo, Ilana Lopes Baratella Cunha ; de Godoy, Mariana Ortiz ; Guido, Rafael Victorio Carvalho ; Oliva, Glaucius ; Santos-Filho, Norival Alves ; Cilli, Eduardo Maffud

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICS; v. 15, n. 2, p. 17-pg., 2023-02-01.

Resumo

Recent studies have shown that the peptide [des-Cys(11),Lys(12),Lys(13)-(p-BthTX-I)(2)K] (p-Bth) is a p-BthTX-I analog that shows enhanced antimicrobial activity, stability and hemolytic activity, and is easy to obtain compared to the wild-type sequence. This molecule also inhibits SARS-CoV-2 viral infection in Vero cells, acting on SARS-CoV-2 PLpro enzymatic activity. Thus, the present study aimed to assess the effects of structural modifications to p-Bth, such as dimerization, dendrimerization and chirality, on the antibacterial activity and inhibitory properties of PLpro. The results showed that the dimerization or dendrimerization of p-Bth was essential for antibacterial activity, as the monomeric structure led to a total loss of, or significant reduction in, bacterial activities. The dimers and tetramers obtained using branched lysine proved to be prominent compounds with antibacterial activity against Gram-positive and Gram-negative bacteria. In addition, hemolysis rates were below 10% at the corresponding concentrations. Conversely, the inhibitory activity of the PLpro of SARS-CoV-2 was similar in the monomeric, dimeric and tetrameric forms of p-Bth. Our findings indicate the importance of the dimerization and dendrimerization of this important class of antimicrobial peptides, which shows great potential for antimicrobial and antiviral drug-discovery campaigns. (AU)

• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 14/50926-0 - INCT 2014: biodiversidade e produtos naturais
• Beneficiário: Vanderlan da Silva Bolzani
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 20/12904-5 - Descoberta de inibidores de Plasmodium falciparum a partir de plantas do Cerrado como candidatos a compostos líderes para a malária: estudos integrados de cromatografia de ultra eficiência, espectroscopia e ensaios biológicos
• Beneficiário: Rafael Victorio Carvalho Guido
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular