Antiviral candidates against the hepatitis E virus (HEV) and their combinations inhibit HEV growth in in vitro.

摘要: Abstract Hepatitis E is a global public health problem. Ribavirin (RBV) and pegylated interferon alpha are currently administered to cure hepatitis E. Recently, in combination with RBV, sofosbuvir (SOF), an anti-hepatitis C virus nucleotide analog, also given patients chronic However, this combinatorial therapy sometimes fails achieve sustained virological response. In study, we used 27 antiviral compounds, including 15 nucleos(t)ide analogs, for vitro screening against genotype 3 HEV strain containing Gaussia luciferase reporter. SOF, 2′-C-methyladenosine, 2′-C-methylcytidine (2CMC), 2′-C-methylguanosine (2CMG), two 4′-azido nucleoside analogs (R-1479 RO-9187) suppressed replication of the reporter genome, while only 2CMC 2CMG inhibited growth cultured cells. Although RBV (2CMG/RBV) exhibited synergistic effect SOF/RBV 2CMC/RBV showed antagonistic effects on assay, these three acted additively inhibiting Furthermore, SOF 2CMG, four interferons (IFN-α2b, IFN-λ1, IFN-λ2 IFN-λ3), efficiently cleared These results suggest that, or interferons, would be promising bases developing anti-HEV analogs.