Antiviral activity of ribavirin and favipiravir against human astroviruses

Background: Recent recognition of invasive astrovirus infections, including encephalitis and viremia in humans, have highlighted the need for effective anti-astrovirus therapeutics. However, there is a paucity of data regarding the in vitro activity of broad-spectrum RNA antivirals against astroviruses, including ribavirin and favipiravir. Objectives: We quantified the EC50 values for ribavirin and favipiravir against two human astrovirus strains, astrovirus VA1 (VA1) and human astrovirus 4 (HAstV4). Study Design: Caco-2 cells were infected with VA1 or HAstV4 in the presence of ribavirin or favipiravir (dose range 0.1-1000 mu M), and the cells were maintained in media containing the drugs for 72 h. Viral RNA was extracted and quantified by qRT-PCR. As a surrogate for cytotoxicity, cellular adenosine triphosphate (ATP) from each drug treatment was also measured. Results: VA1 replication was inhibited 10-100-fold by both ribavirin (EC50 = 154 mu M) and favipiravir (EC50 = 246 mu M). In contrast, ribavirin inhibited HAstV4 replication (EC50 = 268 mu M) but favipiravir only reduced replication by 44% at the highest dose. Mild reductions in ATP (17-31%) was only observed at the highest concentration of ribavirin (1000 mu M) and no significant decrease in ATP was detected for any concentration of favipiravir. Conclusions: Ribavirin inhibited both human astrovirus species and favipiravir was only active against VA1. In the future, the in vivo efficacy of these drugs could be tested with development of an animal model of human astrovirus infection.