S-033447/S-033188, a Novel Small Molecule Inhibitor of Cap-Dependent Endonuclease of Influenza A and B Virus: In Vitro Antiviral Activity Against Clinical Strains

In this study, we tested clinically isolated influenza virus A and B strains that were collected from hospitals in Japan between 2006 and 2014. The geographical and temporal distribution of the viral strains are shown in Figure 2 and Table 1. EC50 values of S-033447 in plaque reduction assay ranged from 0.20 to 0.99 nM for type A and from 4.01 to 11.26 nM for type B, which were typically at least three orders of magnitude lower than those of favipiravir (Figure 3). EC90 values of S-033447 in yield reduction assay ranged from 0.63 to 0.95 nM for type A and from 6.10 to 6.48 nM for type B, which were typically at least three orders of magnitude lower than that of favipiravir (Table 2). No potency shift was observed for S-033447 against virus with NA/H274Y substitution in both assays. These results indicated that S-033447 achieved potent inhibition of influenza viral replication at low nanomolar concentrations. Table 2: EC90 (nM) values of S-033447 and favipiravir against clinically isolated influenza A and B viruses in yield reduction assay