Antiviral Activity of Benzavir-2 against Emerging Flaviviruses

Gwon, Yong-Dae; Strand, Mårten; Lindqvist, Richard; Nilsson, Emma; Saleeb, Michael; Elofsson, Mikael; Överby, Anna K.; Evander, Magnus

Members of the flavivirus genus cause severe morbidity and mortality to mankind worldwide. Since benzavir-2 displayed potent activity against the rZIKV-ZsGreen vector and two wt ZIKV lineages, we assessed if other flaviviruses of medical importance were inhibited. Vero B4 cells were infected with six members of the flavivirus genus (ZIKV, TBEV, WNV, JEV, YFV, or DENV2) in the presence of benzavir-2 (2.5 µM) or ribavirin (50 µM). The supernatant was harvested 24 h or 48 h post-infection and titers were determined by focus-forming assay. Ribavirin showed an approximately ten-fold significant reduction for four of the flaviviruses, ZIKV, TBEV, YFV, and DENV2 (viral titer reduction: ZIKV = 1.0 × 10 1 ; TBEV = 1.2 × 10 1 ; YFV = 0.9 × 10 1 ; and DENV2 = 1.1 × 10 1 ), while no significant activity was detected against JEV and WNV ( Figure 6 ). Strikingly, 2.5 µM of benzavir-2 treatment showed a ≈ 10 3 -10 5 -fold significant reduction of infection in all six flaviviruses analyzed (viral titer reduction in: ZIKV = 1.0 × 10 3 ; TBEV = 7.5 × 10 3 ; WNV = 2.2 × 10 4 ; JEV = 7.5 × 10 3 ; YFV = 1.5 × 10 3 ; and DENV2 = 5.6 × 10 4 ). These results confirmed the potent broad-spectrum activity of benzavir-2.