Evaluation of synthetic peptides on the Chikungunya virus inhibition

Author(s)

Gabriela Miranda Ayusso

• Document type: Doctoral Thesis
• Press: São José do Rio Preto. 2023-05-30.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto
• Defense date: 2023-05-04
• Advisor: Paula Rahal; Marilia de Freitas Calmon

Abstract

Chikungunya virus (CHIKV) has a worldwide distribution and is considered a serious public health problem. The debilitating and chronic nature associated with CHIKV infection and the absence of approved antiviral therapy demonstrate the need for specific drugs that act on the virus's replicative cycle. The discovery of the therapeutic potential of several peptides aroused the interest of the scientific community in this class of substances that has broad biological activity, highlighting the antiviral. The aim of the present work was to evaluate the antiviral potential of the synthetic peptide (p-BthTX-I)2K and the synthetic prototype peptide GA-Hecate and its analogs PSSct1905 and PSSct1910 against CHIKV infection. The cytotoxicity of the peptides was determined in baby hamster kidney fibroblast cells (BHK-21) and/or human hepatocarcinoma epithelial cells (Huh-7) by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The antiviral effect was investigated by measuring the activity of the NanoLuciferase protein, encoded by CHIKV-NLuc. All peptides exhibited inhibitory activity on the CHIKV replication cycle. AG-Hecate and its analog PSSct1905 were the most active, showing an antiviral action greater than 91%. The peptide GA-Hecate and its analogs acted at different stages of the CHIKV replicative cycle in BHK-21 and Huh-7 cells. The analog PSSct1905 demonstrated protective effect on cells against viral infection. CHIKV entry into both cell lines was also affected by peptides PSSct1905 and PSSct1910, triggering inhibition of viral attachment and internalization. Finally, the prototype GA-Hecate and its two analogs showed antiviral activity on the post-entry stages of the viral replication cycle in the two evaluated cells. The peptide (p-BthTX-I)2K, in turn, exhibited anti-CHIKV action by interfering with the early stages of the viral infection cycle. It prevented the entry of CHIKV into BHK-21 cells by inhibiting the viral attachment and internalization steps. Furthermore, it was observed that the inhibitory effect of the peptide (p BthTX-I)2K on viral entry was more significant on attachment than on internalization of CHIKV in BHK-21 cells. Therefore, this study highlighted the peptide (p-BthTX-I)2K and the prototype peptide GA-Hecate and its analogs PSSct1905 and PSSct1910 as promising drug candidates against CHIKV infection. Besides, considering the antiviral properties of these peptides, it is suggested to use their structures as basis for the design of new broad-spectrum antivirals. (AU)

• FAPESP's process: 19/10150-6 - Evaluation of synthetic peptides on Chikungunya Virus inhibition
• Grantee: Gabriela Miranda Ayusso
• Support Opportunities: Scholarships in Brazil - Doctorate