Minimizing Hand Foot And Mouth Disease Effects With Flavonoid Compounds

Hand Foot And Mouth Disease (HFMD) typically affects children and is caused by human enteroviruses. Common symptoms of HFMD include mild fever along with mouth ulcers, rashes on the hand and feet of infected children. Distinctly, in a modest number of cases, human enterovirus A71 (HEVA71) infection can disseminate to the brain and may lead to encephalitis, particularly in neonates.

Due to an unusually high prevalence rate in day-care and childcare facilities, HFMD imposes a rather great social and economic burden in endemic countries in the Asia-Pacific region. Currently, there is no approved therapeutic treatment against the former contagion. In clinics, symptomatic treatment options are routinely used to alleviate the fever and inflammation. Due to the pressing need for a specific antiviral, our group screened a compound library comprising highly purified and naturally derived flavonoids to identify the potential antiviral for HEVA71.

Flavonoids are considered to be safe for human consumption without many adverse effects, and it has been estimated that humans ingest up to 1g of flavonoids daily from their diet. With such ease of availability and over 8,000 identified flavonoids so far, it is our ultimate aim to find a prevention or cure for childhood diseases such as HEVA71-associated HFMD in flavonoids that are commonly found and ingested through food sources.

We identified two lead flavonoid compounds, ST077124 (Quercetagetin) and ST024734 as effective antivirals that inhibited replication of HEVA71 by reducing infectious viral titers by 3.5 log10 PFU/ml and 2.5 log10 PFU/ml respectively with 50 μM post-treatment in the cell-based assay. Our study reveals ST077124 to be a limited spectrum antiviral compound that is inhibitory against human enteroviruses while ST024734 exhibited antiviral activity against human enteroviruses as well as mosquito-borne dengue virus. Given their plant metabolite origins, the lack of toxicity by the flavonoids was hardly surprising, and we observed that even at relatively high concentration treatments, the flavonoids were still well tolerated by human cell lines.

ST077124 (Quercetagetin) is a major flavonoid found abundantly in peels of citrus fruits such as tangerine. Functional foods are gaining traction recently as preventative and supportive medicines for various diseases. Here, our findings strongly suggest that ST077124 and ST024734 are effective antiviral compounds with minimal cytotoxicity against enterovirus infections. Although we typically do not consume peels of tangerine, flavonoids ingested through those unconventional functional food sources such as citrus peel powder may serve as promising therapeutic or preventive agents against the notorious hand foot and mouth disease.

These findings are described in the article entitled A flavonoid compound library screen revealed potent antiviral activity of plant-derived flavonoids on human enterovirus A71 replication, recently published in the journal Antiviral Research. This work was conducted by Nyo Min, Pok Thim Leong, Regina Ching Hua Lee, and Justin Jang Hann Chu from the National University of Singapore, and Jeffery Seng Eng Khuan from the Nanyang Polytechnic.

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