In silico and biological characterization of peptides present in the venom of the scorpion Tityus serrulatus

Author(s)

Lais Gomes da Silva

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2023-05-02

Examining board members

Fernanda Calheta Vieira Portaro; Daniela Cajado de Oliveira Souza Carvalho; Kelly Ishida; Carlos Alberto da Silva

• Advisor: Fernanda Calheta Vieira Portaro; Giselle Pidde Marques Porto

Abstract

Scorpionism is considered a public health problem in tropical and subtropical countries. In Brazil, the species Tityus serrulatus is the mainly responsible for accidents due to the toxicity of its venom. Recent studies have shown that T. serrulatus venom is mostly composed of peptides, most of which have unknown biological functions. In this scenario, our group has been working on the selection of low molecular weight peptides for a better understanding of the venom and for the biotechnological development of new drugs. The main objective was to perform in silico analyses of 700 peptide sequences found in T. serrulatus venom, previously identified by our group, and to evaluate the biological function of the synthesized peptides. The in silico analyses were performed on bioinformatics platforms focusing on antimicrobial, antihypertensive, immunomodulatory, hemolytic and toxic activities. The in silico analyses indicated that 21 sequences may present biotechnological potential of interest and, after refinement the analysis, 12 sequences were selected for synthesis. The activities of the synthetic peptides were evaluated in in vitro and cellular tests. The verification of antihypertensive activity was verified using angiotensin I converting enzyme (ACE I), and our results showed that five peptides are competitive inhibitors of ACE I, among which, three stood out as having Ki between 0.34 μM and 0.81 μM. We also found that two of the peptides showed higher specificity for inhibiting of the ACE I C site, indicating a biotechnological potential for these molecules. In the antimicrobial assays performed, some peptides showed higher inhibition for Staphylococcus aureus and Candida albicans, with inhibition above 40% of the growth of these microorganisms, without showing hemolytic effects on human erythrocytes. In our immunomodulation assays, three peptides mildly induced some proinflammatory cytokines, and these also reduced the growth of C. albicans, thus pointing to possible biotechnological applications of these molecules. Further characterization of these molecules may help to understand the mechanism of action of the venom during envenomation, as well as serve as a prototype for the development of new drugs. (AU)

• FAPESP's process: 20/01213-1 - In silico and biological characterization of peptides present in scorpion venom Tityus serrulatus
• Grantee: Lais Gomes da Silva
• Support Opportunities: Scholarships in Brazil - Master