In recent decades, chikungunya virus (CHIKV) has re-emerged, leading to outbreaks of
chikungunya fever in Africa, Asia and Central and South America. The disease is characterized by a rapid onset febrile illness with (poly)
arthralgia,
myalgia, rashes,
headaches and
nausea. In 30 to 40% of the cases, CHIKV
infection causes persistent (poly)
arthralgia, lasting for months or even years after initial
infection. Despite the drastic re-emergence and clinical impact there is no
vaccine nor
antiviral compound available to prevent or control CHIKV
infection. Here, we evaluated the
antiviral potential of
tomatidine towards CHIKV
infection. We demonstrate that
tomatidine potently inhibits virus particle production of multiple CHIKV strains. Time-of -addition experiments in Huh7 cells revealed that
tomatidine acts at a post-entry step of the virus replication cycle. Furthermore, a marked decrease in the number of CHIKV-infected cells was seen, suggesting that
tomatidine predominantly acts early in
infection yet after virus attachment and cell entry.
Antiviral activity was still detected at 24 hours post-
infection, indicating that
tomatidine controls multiple rounds of CHIKV replication.
Solasodine and
sarsasapogenin, two structural derivatives of
tomatidine, also showed strong albeit less potent
antiviral activity towards CHIKV. In conclusion, this study identifies
tomatidine as a novel compound to combat CHIKV
infection in vitro.