Antivirals against the Chikungunya Virus

Abstract

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has re-emerged in recent decades, causing large-scale epidemics in many parts of the world. CHIKV infection leads to a febrile disease known as chikungunya fever (CHIKF), which is characterised by severe joint pain and myalgia. As many patients develop a painful chronic stage and neither antiviral drugs nor vaccines are available, the development of a potent CHIKV inhibiting drug is crucial for CHIKF treatment. A comprehensive summary of current antiviral research and development of small-molecule inhibitor against CHIKV is presented in this review. We highlight different approaches used for the identification of such compounds and further discuss the identification and application of promising viral and host targets.

The Antifungal Itraconazole Is a Potent Inhibitor of Chikungunya Virus Replication

“…Another antiviral identified was GSK-983, a tetrahydrocarbazole inhibitor of the dihydroorotate dehydrogenase (DHODH) [ 37 ]. DHODH and other enzymes of the pyrimidine biosynthesis pathway are investigated as targets of broad-spectrum antivirals, including the ones with anti-CHIKV activities such as atovaquone, RYL-634, and DD363, but targeting host factors may interfere with cell viability (reviewed in [ 38 ]). This could explain the lower CC 50 observed in replicon-based assays, in which cells are incubated with the compound for a longer period of time than that for the viral infection assays.…”

MBZM-N-IBT, a Novel Small Molecule, Restricts Chikungunya Virus Infection by Targeting nsP2 Protease Activity In Vitro , In Vivo , and Ex Vivo

“…The increase in disease incidences and persistent CHIKV-induced arthritis-like symptoms have been a huge burden on public health across the globe. In the absence of any specific antiviral for CHIKV, it is essential to continue efforts to develop an effective antiviral strategy against this virus ( 30 , 31 ). The earlier findings that showed the potential of MBZM-N-IBT to inhibit CHIKV in vitro encouraged us to further validate its efficacy ( 21 ).…”

“…Interestingly, in normal host cells, MBZM-N-IBT did not affect the immunomodulatory host factors (IFN-β, TNF-α, MCP-1, and OAS1). However, several reports suggested that the pretreatment with type I interferon (IFN) signaling inducers (viperin, 50pppRNA, and its analogue M8) can control and prevent CHIKV infections ( 30 ). Agonists of the STING pathway were also known to limit alphavirus infection ( 44 ).…”

A Review on Chikungunya Virus Epidemiology, Pathogenesis and Current Vaccine Development

“…Different approaches were employed by several research groups to identify novel potential CHIKV antiviral drugs and drug candidates that have been repurposed to inhibit CHIKV replication; however, none of them are currently under clinical evaluation. An up-to-date and complete review of these findings is presented by Hucke and Burget (2020) [ 102 ] and Battisti et al (2021) [ 103 ].…”