Antiviral Activity of the Combination of Interferon and Ribavirin Against Chikungunya Virus: Are the Results Conclusive?

The evaluation of the antiviral activity performed to support the development of an “investigational” product should include an assay directed against a broad range of clinical and laboratory viral isolates, including different clades, subtypes, or genotypes. To this regard, we found that the envelope surface glycoprotein E1 (A226V) adaptive mutation, which improved the fitness of CHIKV for a secondary vector, Aedes albopictus (facilitating its spread during the outbreaks in the Indian Ocean area, in India and in north-eastern Italy), can significantly affect the sensitivity of CHIKV to the antiviral action of different type I IFN preparations. In particular, CHIKV strain (East Central South African [ECSA]) with the A226V mutation was more sensitive to IFNs in the Vero cell line compared to the viral strain without A226V. Second, the assessment of antiviral activity to support the development of an “investigational” product requires to test at least the effect of an increasing multiplicity of infection (MOI) and, whenever possible, the antiviral activity in different cellular lines, giving priority to human cells (which are more likely to reflect in vivo condition). In this context, we found that the antiviral activity of IFNs against CHIKV strains significantly decreased by increasing the MOI. Furthermore, the authors estimated the antiviral activity of IFNα2a against CHIKV in Vero cells only. In relation to that, we found that the antiviral activity of IFNα, IFNβ, and IFNω against both strains of CHIKV is different in Hep-2, a human cell line, compared to that recorded in Vero cells.