Evaluation of in vitro inhibitory potential of type-I interferons and different antiviral compounds on rabies virus replication.

Five different compounds were tested for their in vitro inhibitory effect against RABV multiplication in mouse neuroblastoma (N2A) cell line. N2A cells were infected with the fixed RABV strain CVS-11 one hour prior to adding antivirals or their respective combinations. The infectious titre of RABV as well as the quantity of viral RNA was determined in the cell culturing medium after 48 h. All five tested compounds (mouse interferon (IFN)-α and -β, ribavirin, favipiravir (T-705) and sorafenib) reduced viral replication in a concentration-dependent manner: IFN-β and sorafenib both provided 73.71% relative inhibition of viral replication in the highest non-cytotoxic concentration, while ribavirin caused 48.07%, IFN-α caused 44.87% and favipiravir caused 35.25% relative inhibition, respectively. When applied in combination, their antiviral activity was not synergistic, but a pronounced inhibition was detected when IFN-β was combined with sorafenib, ribavirin, or favipiravir. The highest antiviral effect was caused by the combination of IFN-β and sorafenib (77.19% relative inhibition). In other combinations there was an antagonistic effect detected in the reduction of viral replication. The results demonstrate that these compounds can be promising candidates for a potential combination treatment of rabies, noting that some combinations are not favourable in vitro, which makes thorough in vivo studies necessary.