Abstract
Rhubarb (Rheum tanguticum; da-huang in Chinese medicine) is a herbal medicine that has been used widely for managing fever and removing toxicity. In this study, we investigated how rhubarb inhibits influenza virus during the early stage of the infectious cycle using different functional assays. A non-toxic ethanolic extract of rhubarb (Rex) inhibited several H1N1 subtypes of influenza A viruses in Madin–Darby canine kidney cells, including strains that are clinically resistant to oseltamivir. Time course analysis of Rex addition showed that viral entry was one of the steps that was inhibited by Rex. We also confirmed that Rex effectively inhibited viral attachment and penetration into the host cells. The inhibition of red blood cell haemolysis and cell–cell fusion by Rex suggests that Rex may block haemagglutinin-mediated fusion (virus–endosome fusion) during the fusion/uncoating step. Rex has the capacity to inhibit influenza viruses by blocking viral endocytosis. Thus, rhubarb might provide an alternative therapeutic approach when resistant viruses become more prevalent.
Highlights
Influenza viruses belong to the Orthomyxoviridae family and they possess negative-sense, single-stranded, and segmented RNA genomes
The spectrum of inhibition in Madin–Darby canine kidney (MDCK) cells suggested that Rex inhibited all of the H1N1 subtypes among influenza A virus strains, including H1N1pdm strains and strains that are clinically resistant to oseltamivir (Table 1)
Rex had more specific effects against the H1N1 subtypes of influenza A virus. We confirmed this Rex-mediated inhibition based on the virus-induced cytopathic effect (CPE) observed by microscopy (Fig. 1)
Summary
Influenza viruses belong to the Orthomyxoviridae family and they possess negative-sense, single-stranded, and segmented RNA genomes. Current anti-influenza virus drug development is focused on interfering with the viral life cycle. Drugs that target the proton channel formed by the viral M2 protein of influenza A virus are used clinically, such as adamantanes (amantadine and rimantadine)[9]. NA inhibitors (NAIs) can prevent virus particle budding and release, and orally bioavailable oseltamivir and inhaled zanamivir belong to the NAI class of drugs. These two drugs are currently recommended for the treatment of both influenza A and influenza B viruses. In the present study, we used various functional assays to determine the stage of the viral life cycle inhibited by rhubarb and we investigated the underlying antiviral mechanism
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