Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes severe and often persistent
arthritis. In recent years, millions of people have been infected with this virus for which registered
antivirals are still lacking. Using our recently established in vitro assay, we discovered that the approved anti-parasitic
drug suramin inhibits CHIKV
RNA synthesis (IC50 of ∼5μM). The compound inhibited replication of various CHIKV isolates in cell culture with an EC50 of ∼80μM (CC50>5mM) and was also active against Sindbis virus and Semliki Forest virus. In vitro studies hinted that
suramin interferes with (re)initiation of
RNA synthesis, whereas time-of-addition studies suggested it to also interfere with a post-attachment early step in
infection, possibly entry. CHIKV (nsP4) mutants resistant against
favipiravir or
ribavirin, which target the
viral RNA polymerase, did not exhibit cross-resistance to
suramin, suggesting a different mode of action. The assessment of the activity of a variety of
suramin-related compounds in cell culture and the in vitro assay for
RNA synthesis provided more insight into the moieties required for
antiviral activity. The
antiviral effect of
suramin-containing
liposomes was also analyzed. Its approved status makes it worthwhile to explore the use of
suramin to prevent and/or treat CHIKV
infections.