Executive Summary : | Chikungunya disease is a mosquito-borne viral infection caused by the chikungunya virus (CHIKV). It is characterized by acute febrile illness, rashes, and severe arthralgia that resolves within 1-2 weeks. However, in 30-40% of infected individuals, this phase is followed by chronic disease, affecting mobility and quality of life. There is no vaccine or therapeutic for chikungunya disease, and the search for a safe and immunogenic vaccine continues worldwide. There is an urgent need to develop small-molecule antivirals against chikungunya as a first line of treatment in case of widespread outbreaks. In vitro antiviral drug screening assays are vital in the drug discovery pipeline. This study proposes developing in vitro high throughput antiviral drug screening assays and chikungunya disease mouse models. The conventional plaque assay is a reliable method for chikungunya virus titration, but adapting it to a high throughput platform is challenging. The proposed high throughput platform will use an infectivity assay for drug screening against CHIKV, which will determine the virus infection level using cell-ELISA using E2-specific antibodies. An infectivity reduction assay will be developed as a cheaper alternative to cell ELISA. Variations of the infectivity assay will be developed to test the activity of compounds to inhibit virus-cell attachment, entry, replication, and release. In vitro drug screening assays followed by in vivo evaluation remain a foundation in the drug discovery pipeline against infectious diseases. CSIR-CDRI's team of medicinal and process chemists can spearhead the effort to develop drugs against chikungunya infection. |