Autor(es): Rothan Hussin A, Bahrani Hirbod, Abdulrahman Ammar Y, Mohamed Zulqarnain, Teoh Teow Chong, Othman Shatrah, Rashid Nurshamimi Nor, Rahman Noorsaadah A, Yusof Rohana

Resumo: Chikungunya virus (CHIKV) infection is a persistent problem worldwide due to efficient adaptation of the viral vectors, Aedes aegypti - Aedes albopictus mosquitoes. Therefore, the absence of effective anti-CHIKV drugs to combat chikungunya outbreaks often leads to a significant impact on public health care. In this study, we investigated the antiviral activity of drugs that are used to alleviate infection symptoms, namely, the non-steroidal anti-inflammatory drugs (NSAIDs), on the premise that active compounds with potential antiviral - anti-inflammatory activities could be directly subjected for human use to treat CHIKV infections. Amongst the various NSAID compounds, Mefenamic acid (MEFE) - Meclofenamic acid (MECLO) showed considerable antiviral activity against viral replication individually or in combination with the common antiviral drug, Ribavirin (RIBA). The 50% effective concentration (EC50) was estimated to be 13 ?M for MEFE, 18 ?M for MECLO - 10 ?M for RIBA, while MEFE + RIBA (1:1) exhibited an EC50 of 3 ?M, - MECLO + RIBA (1:1) was 5 ?M. Because MEFE is commercially available - its synthesis is easier compared with MECLO, MEFE was selected for further in vivo antiviral activity analysis. Treatment with MEFE + RIBA resulted in a significant reduction of hypertrophic effects by CHIKV on the mouse liver - spleen. Viral titre quantification in the blood of CHIKV-infected mice through the plaque formation assay revealed that treatment with MEFE + RIBA exhibited a 6.5-fold reduction compared with untreated controls. In conclusion, our study demonstrated that MEFE in combination with RIBA exhibited significant anti-CHIKV activity by impairing viral replication in vitro - in vivo. Indeed, this finding may lead to an even broader application of these combinatorial treatments against other viral infections.

Palavras-Chave: Chikungunya virus; Meclofenamic acid; Mefenamic acid; Non-steroidal anti-inflammatory drugs; Ribavirin

Imprenta: Antiviral Research, v. 127, p. 50-56, 2016

Identificador do Objeto Digital: 10.1016/j.antiviral.2016.01.006

Descritores: Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Public health

Data de Publicação: 2016