A Novel Sphingosine Kinase Inhibitor Suppresses Chikungunya Virus Infection

Opeoluwa O. Oyewole, Kyle Dunnavant, Shaurav Bhattarai, Yugesh Kharel, Kevin R. Lynch, Webster L. Santos, St Patrick Reid

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Chikungunya virus (CHIKV) is a re-emerging arbovirus in the alphavirus genus. Upon infection, it can cause severe joint pain that can last years in some patients, significantly affecting their quality of life. Currently, there are no vaccines or anti-viral therapies available against CHIKV. Its spread to the Americas from the eastern continents has substantially increased the count of the infected by millions. Thus, there is an urgent need to identify therapeutic targets for CHIKV treatment. A potential point of intervention is the sphingosine-1-phosphate (S1P) pathway. Conversion of sphingosine to S1P is catalyzed by Sphingosine kinases (SKs), which we previously showed to be crucial pro-viral host factor during CHIKV infection. In this study, we screened inhibitors of SKs and identified a novel potent inhibitor of CHIKV infection—SLL3071511. We showed that the pre-treatment of cells with SLL3071511 in vitro effectively inhibited CHIKV infection with an EC50 value of 2.91 µM under both prophylactic and therapeutic modes, significantly decreasing the viral gene expression and release of viral particles. Our studies suggest that targeting SKs is a viable approach for controlling CHIKV replication.

Original languageEnglish (US)
Article number1123
JournalViruses
Volume14
Issue number6
DOIs
StatePublished - Jun 2022

Keywords

  • Chikungunya virus
  • SLL3071511 inhibitor
  • Sphingosine kinase 2
  • antiviral
  • drug discovery

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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