Inhibitory effects of a peptide-fusion protein (Latarcin-PAP1-Thanatin) against Chikungunya virus

Autor(es): Rothan Hussin A, Bahrani Hirbod, Shankar Esaki M, Rahman Noorsaadah Abd, Yusof Rohana


Resumo: Chikungunya virus (CHIKV) outbreaks have led to a serious economic burden, as the available treatment strategies can only alleviate disease symptoms, - no effective therapeutics or vaccines are currently available for human use. Here, we report the use of a new cost-effective approach involving production of a recombinant antiviral peptide-fusion protein that is scalable for the treatment of CHIKV infection. A peptide-fusion recombinant protein LATA-PAP1-THAN that was generated by joining Latarcin (LATA) peptide with the N-terminus of the PAP1 antiviral protein, - the Thanatin (THAN) peptide to the C-terminus, was produced in Escherichia coli as inclusion bodies. The antiviral LATA-PAP1-THAN protein showed 89.0% reduction of viral plaque formation compared with PAP1 (46.0%), LATA (67.0%) or THAN (79.3%) peptides alone. The LATA-PAP1-THAN protein reduced the viral RNA load that was 0.89-fold compared with the untreated control cells. We also showed that PAP1 resulted in 0.44-fold reduction, - THAN - LATA resulting in 0.78-fold - 0.73-fold reductions, respectively. The LATA-PAP1-THAN protein inhibited CHIKV replication in the Vero cells at an EC50 of 11.2?g/ml, which is approximately half of the EC50 of PAP1 (23.7?g/ml) - protected the CHIKV-infected mice at the dose of 0.75mg/ml. We concluded that production of antiviral peptide-fusion protein in E. coli as inclusion bodies could accentuate antiviral activities, enhance cellular internalisation, - could reduce product toxicity to host cells - is scalable to epidemic response quantities.


Palavras-Chave: Antiviral activity; Chikungunya virus; Fusion protein; Latarcin; Tachyplesin1; Thanatin


Imprenta: Antiviral Research, v. 108, p. 173-180, 2014


Identificador do objeto digital: 10.1016/j.antiviral.2014.05.019


Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic


Data de publicação: 2014