Mefenamic acid in combination with ribavirin shows significant effects in reducing chikungunya virus infection in vitro and in vivo.

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 and 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 and anti-inflammatory activities could be directly subjected for human use to treat CHIKV infections. Amongst the various NSAID compounds, Mefenamic acid (MEFE) and 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 and 10 ?M for RIBA, while MEFE + RIBA (1:1) exhibited an EC50 of 3 ?M, and MECLO + RIBA (1:1) was 5 ?M. Because MEFE is commercially available and 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 and 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 and in vivo. Indeed, this finding may lead to an even broader application of these combinatorial treatments against other viral infections.

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

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

Identificador do objeto digital: 10.1016/j.antiviral.2016.01.006

Descritores: Aedes aegypti - Viral infections ; Aedes aegypti - Public health ; Aedes aegypti - Virus

Data de publicação: 2016