The Dimeric Peptide (KKYRYHLKPF)(2)K Shows Broad-Spectrum Antiviral Activity by Inhibiting Different Steps of Chikungunya and Zika Virus Infection

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Ayusso, Gabriela Miranda ; Lima, Maria Leticia Duarte ; Sanches, Paulo Ricardo da Silva ; Santos, Igor Andrade ; Martins, Daniel Oliveira Silva ; da Conceicao, Pamela Joyce Previdelli ; Carvalho, Tamara ; da Costa, Vivaldo Gomes ; Bittar, Cintia ; Merits, Andres ; Santos-Filho, Norival Alves ; Cilli, Eduardo Maffud ; Jardim, Ana Carolina Gomes ; Calmon, Marilia de Freitas ; Rahal, Paula

• Document type: Journal article
• Source: Viruses-Basel; v. 15, n. 5, p. 17-pg., 2023-05-14.

Abstract

Chikungunya virus (CHIKV) and Zika virus (ZIKV) are important disease-causing agents worldwide. Currently, there are no antiviral drugs or vaccines approved to treat these viruses. However, peptides have shown great potential for new drug development. A recent study described (p-BthTX-I)(2)K [(KKYRYHLKPF)(2)K], a peptide derived from the Bothropstoxin-I toxin in the venom of the Bothrops jararacussu snake, showed antiviral activity against SARS-CoV-2. In this study, we assessed the activity of this peptide against CHIKV and ZIKV and its antiviral action in the different stages of the viral replication cycle in vitro. We observed that (p-BthTX-I)(2)K impaired CHIKV infection by interfering with the early steps of the viral replication cycle, reducing CHIKV entry into BHK-21 cells specifically by reducing both the attachment and internalization steps. (p-BthTX-I)(2)K also inhibited the ZIKV replicative cycle in Vero cells. The peptide protected the cells against ZIKV infection and decreased the levels of the viral RNA and the NS3 protein of this virus at viral post-entry steps. In conclusion, this study highlights the potential of the (p-BthTX-I)(2)K peptide to be a novel broad-spectrum antiviral candidate that targets different steps of the replication cycle of both CHIKV and ZIKV. (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
• FAPESP's process: 19/07784-3 - In vitro study of the action of synthetic peptides as antivirals against CHIKV
• Grantee: Marilia de Freitas Calmon
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/00603-3 - Analysis of the virome from ticks collected from wild animals
• Grantee: Paula Rahal
• Support Opportunities: Regular Research Grants