Chikungunya virus infection - Emerging treatments

Chloroquine

Chloroquine is theoretically effective against chikungunya virus by means of inhibition of viral enzymes, prevention of virus entry, impairment of viral maturation, or by enhancement of the immunological response to the infection. An old open pilot study in 10 patients receiving chloroquine for 20 weeks suggested subjective and objective improvement in the majority of patients, including decrease in morning stiffness and lower numbers in the Ritchie Articular Index (a numerical assessment of articular pain in patients with rheumatoid arthritis).[84] However, a 2008 community-based intervention trial among more than 500 patients failed to show an advantage of chloroquine over meloxicam (a non-steroidal anti-inflammatory drug) to treat early musculoskeletal pain and arthritis following acute infection.[85] A placebo-controlled trial in 54 patients showed that patients receiving chloroquine had more arthralgia than patients receiving placebo 200 days after the infection occurred.[86]

Ribavirin

Ribavirin has antiviral activity in vitro against chikungunya virus and synergistic effects in combination with interferon. However, its use in clinical practice is quite sparse. In 7 out of 10 patients with crippling pain, ribavirin seemed to be effective, alleviating the pain and allowing patients to recover their ability to walk after a 7-day course of therapy.[87]

Interferon

Adenovirus-vectored interferon injected in mice has a preventive effect against arthralgia when used within 24 hours after a challenge with chikungunya virus. In vitro studies also suggest inhibition of viral replication in Vero cells, an action that is synergistically enhanced by the concomitant use of ribavirin.[88][89]

Other therapies

There are many other therapies that are currently under development, including umifenovir, 6-azauridine, decanoyl-RVKR-CMK, 5,7 dihydroxyflavones, harringtonine, mycophenolic acid, chlorpromazine, polyinosinic:polycytidylic acid, small interfering RNA, and trigocherrierin A.[89][90][91][92][93][94][95][96][97][98][99] However, these drugs are only in the very early stages of clinical studies. Drug discovery studies are focusing on viral replicase inhibitors and inhibition of heat shock protein HSP90, kinases, and other cellular signalling pathways.[10] Existing immunotherapies such as fingolimod, abatacept, and tofacitinib are also being studied.[100][101]