Autor(es): Lam Shirley, Chen Huixin, Chen Caiyun Karen, Min Nyo, Chu Justin Jang Hann

Resumo: Chikungunya virus (CHIKV) infection in human is associated with debilitating - persistent arthralgia - arthritis. Currently, there is no specific vaccine or effective antiviral available. Anti-CHIKV Phosphorodiamidate Morpholino Oligomer (CPMO) was evaluated for its antiviral efficacy - cytotoxcity in human cells - neonate murine model. Two CPMOs were designed to block translation initiation of a highly conserved sequence in CHIKV non-structural - structural polyprotein, respectively. Pre-treatment of HeLa cells with CPMO1 significantly suppressed CHIKV titre, CHIKV E2 protein expression - prevented CHIKV-induced CPE. CPMO1 activity was also CHIKV-specific as shown by the lack of cross-reactivity against SINV or DENV replication. When administered prophylactically in neonate mice, 15 ?g/g CPMO1v conferred 100% survival against CHIKV disease. In parallel, these mice demonstrated significant reduction in viremia - viral load in various tissues. Immunohistological examination of skeletal muscles - liver of CPMO1v-treated mice also showed healthy tissue morphology, in contrast to evident manifestation of CHIKV pathogenesis in PBS- or scrambled sCPMO1v-treated groups. Taken together, our findings highlight for the first time that CPMO1v has strong protective effect against CHIKV infection. This warrants future development of morpholino as an alternative antiviral agent to address CHIKV infection in clinical applications.

Palavras-Chave: Alphaviruses; Antivirals

Imprenta: Scientific Reports, v. 5, p. 12727, 2015

Identificador do objeto digital: 10.1038/srep12727

Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - RNA ; Chikungunya virus - Clinical examination ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine

Data de publicação: 2015

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