The Dimeric Peptide (KKYRYHLKPF)<sub>2</sub>K Shows Broad-Spectrum Antiviral Activity by Inhibiting Different Steps of Chikungunya and Zika Virus Infection
Gabriela Miranda Ayusso,
Maria Letícia Duarte Lima,
Paulo Ricardo da Silva Sanches,
Igor Andrade Santos,
Daniel Oliveira Silva Martins,
Pâmela Jóyce Previdelli da Conceição,
Tamara Carvalho,
Vivaldo Gomes da Costa,
Cíntia Bittar,
Andres Merits,
Norival Alves Santos-Filho,
Eduardo Maffud Cilli,
Ana Carolina Gomes Jardim,
Marilia de Freitas Calmon,
Paula Rahal
Affiliations
Gabriela Miranda Ayusso
Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil
Maria Letícia Duarte Lima
Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil
Paulo Ricardo da Silva Sanches
School of Pharmaceutical Sciences, São Paulo State University, Araraquara 14800-903, SP, Brazil
Igor Andrade Santos
Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia 38408-100, MG, Brazil
Daniel Oliveira Silva Martins
Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil
Pâmela Jóyce Previdelli da Conceição
Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil
Tamara Carvalho
Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil
Vivaldo Gomes da Costa
Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil
Cíntia Bittar
Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil
Andres Merits
Institute of Technology, University of Tartu, 50090 Tartu, Estonia
Norival Alves Santos-Filho
Institute of Chemistry, São Paulo State University, Araraquara 14800-060, SP, Brazil
Eduardo Maffud Cilli
Institute of Chemistry, São Paulo State University, Araraquara 14800-060, SP, Brazil
Ana Carolina Gomes Jardim
Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil
Marilia de Freitas Calmon
Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil
Paula Rahal
Institute of Biosciences, Letters and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil
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)2K [(KKYRYHLKPF)2K], 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)2K 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)2K 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)2K peptide to be a novel broad-spectrum antiviral candidate that targets different steps of the replication cycle of both CHIKV and ZIKV.
