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

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dc.contributor.authorBitencourt, Natália Vitória [UNESP]
dc.contributor.authorRighetto, Gabriela Marinho
dc.contributor.authorCamargo, Ilana Lopes Baratella Cunha
dc.contributor.authorde Godoy, Mariana Ortiz
dc.contributor.authorGuido, Rafael Victorio Carvalho
dc.contributor.authorOliva, Glaucius
dc.contributor.authorSantos-Filho, Norival Alves [UNESP]
dc.contributor.authorCilli, Eduardo Maffud [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2023-07-29T13:44:08Z
dc.date.available2023-07-29T13:44:08Z
dc.date.issued2023-02-01
dc.description.abstractRecent studies have shown that the peptide [des-Cys11,Lys12,Lys13-(p-BthTX-I)2K] (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.en
dc.description.affiliationDepartment of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), SP
dc.description.affiliationSão Carlos Institute of Physics University of São Paulo, SP
dc.description.affiliationUnespDepartment of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), SP
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.identifierhttp://dx.doi.org/10.3390/pharmaceutics15020436
dc.identifier.citationPharmaceutics, v. 15, n. 2, 2023.
dc.identifier.doi10.3390/pharmaceutics15020436
dc.identifier.issn1999-4923
dc.identifier.scopus2-s2.0-85149136177
dc.identifier.urihttp://hdl.handle.net/11449/248440
dc.language.isoeng
dc.relation.ispartofPharmaceutics
dc.sourceScopus
dc.subjectantimicrobial peptide
dc.subjectCOVID-19
dc.subjectdendrimers
dc.subjectmultidrug-resistant bacteria
dc.subjectp-Bth
dc.subjectp-BthTX-I
dc.subjectPLpro
dc.subjectSARS-CoV-2
dc.titleEffects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PLpro Proteinen
dc.typeArtigo
unesp.author.orcid0000-0003-2918-2162[1]
unesp.author.orcid0000-0002-7187-0818[5]
unesp.author.orcid0000-0003-2719-0302[6]
unesp.author.orcid0000-0002-0344-6900[7]

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