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  1. Rufaidah Othman, Saiful Anuar Karsani, Rozana Othman, Aida Baharuddin, Ramakrishnan NR, Noorsaadah Abd. Rahman, et al.
    Sains Malaysiana, 2017;46:1865-1875.
    Dengue is a potentially deadly disease with no effective drug. An in silico molecular docking was performed using Autodock
    4.2.6 to investigate the molecular interactions between protease inhibitors, comprising antibiotic derivatives namely
    doxycycline (3), rolitetracycline (5) and a non-steroidal anti-inflammatory drug (NSAID), meclofenamic acid (4), against
    the NS2B-NS3 protease from dengue virus-2 (DENV-2). The non-competitive inhibitor (3) showed lower binding energy
    (-5.15 kcal/mol) than the predicted competitive inhibitors 4 and 5 (-3.64 and -3.21 kcal/mol, respectively). Structural
    analyses showed compound 3 that bound to a specific allosteric site, interacted with Lys74, a significant amino acid
    residue bonded to one of the catalytic triad, Asp75. Compounds 4 and 5 showed direct binding with two of the catalytic
    triad, His51 and Ser135, hence, predicted to be competitive inhibitors.
    Matched MeSH terms: Meclofenamic Acid
  2. Rothan HA, Bahrani H, Abdulrahman AY, Mohamed Z, Teoh TC, Othman S, et al.
    Antiviral Res, 2016 Mar;127:50-6.
    PMID: 26794398 DOI: 10.1016/j.antiviral.2016.01.006
    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 μM for MEFE, 18 μM for MECLO and 10 μM for RIBA, while MEFE + RIBA (1:1) exhibited an EC50 of 3 μM, and MECLO + RIBA (1:1) was 5 μM. 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.
    Matched MeSH terms: Meclofenamic Acid
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