Chikungunya virus (CHIKV) infection in human is associated with debilitating and persistent arthralgia and arthritis. Currently, there is no specific vaccine or effective antiviral available. Anti-CHIKV Phosphorodiamidate Morpholino Oligomer (CPMO) was evaluated for its antiviral efficacy and cytotoxcity in human cells and neonate murine model. Two CPMOs were designed to block translation initiation of a highly conserved sequence in CHIKV non-structural and structural polyprotein, respectively. Pre-treatment of HeLa cells with CPMO1 signficantly suppressed CHIKV titre, CHIKV E2 protein expression and 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 mu g/g CPMO1v conferred 100% survival against CHIKV disease. In parallel, these mice demonstrated significant reduction in viremia and viral load in various tissues. Immunohistological examination of skeletal muscles and 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.
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US Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USAUS Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA
Warren, Travis K.
Whitehouse, Chris A.
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US Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USAUS Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA
Whitehouse, Chris A.
Wells, Jay
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US Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USAUS Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA
Wells, Jay
Welch, Lisa
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US Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USAUS Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA
Welch, Lisa
Heald, Alison E.
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Sarepta Therapeut Inc, Cambridge, MA USA
Univ Washington, Seattle, WA 98195 USAUS Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA
Heald, Alison E.
Charleston, Jay S.
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Sarepta Therapeut Inc, Cambridge, MA USAUS Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA
Charleston, Jay S.
Sazani, Pete
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Sarepta Therapeut Inc, Cambridge, MA USAUS Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA
Sazani, Pete
Reid, St Patrick
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US Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USAUS Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA
Reid, St Patrick
Iversen, Patrick L.
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Sarepta Therapeut Inc, Cambridge, MA USA
Oregon State Univ, Corvallis, OR 97331 USAUS Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA
Iversen, Patrick L.
Bavari, Sina
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US Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USAUS Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA