ntrol influenza virus infection; however, annual vaccination has some disadvantages and limitations, including high cost, inadequate protection, and the considerable length of time required to design and produce the vaccine. Therefore, efficient control of influenza outbreaks requires the discovery and development of novel antiviral drugs. There are two categories of anti-influenza drugs: the neuraminidase inhibitors such as oseltamivir and zanamivir that have been approved in many countries worldwide, while peramivir and laninamivir are approved in Japan and peramivir is approved in China and the Republic of Korea. In MK886 chemical information addition, the M2 proton channel inhibitors amantadine and its derivative rimantadine that stop the infection immediately after their administration. Unfortunately, the dramatic increase in the resistance of influenza A/H1N1 against Tamiflu, amantadine, and rimantadine has incited the worldwide concern. Recently, there is an increase in the Tamiflu resistance in the clinical isolates; probably due to increase in the fitness of H275Y resistant mutant that leads to NA and HA mutations as a consequence. Therefore, novel and safe anti-influenza drugs are a focus of drug development programs, and natural antiviral nutrients are of special interest, because they are widely available and may be used as dietary supplements to combat diseases, including influenza infection. Polyphenolic flavonoid compounds are ingested daily in the diet due to their widespread availability in fruits, vegetables, grains, tea, and wine. Dietary flavonoids have several well-established therapeutic effects and produce beneficial impacts on human health such as, immunomodulation, antibacterial, anti-fungal, anti-inflammatory, anti-oxidant, and anti-cancer activities. Of note, there is various flavonoids showed strong anti-influenza virus property in vitro. Interestingly, the flavonoids showed strong synergetic effect when with ribavirin in mice.The chemical structure of the flavonoids is based on the presence of a 15-carbon skeleton consisting of two benzene rings connected by a heterocyclic pyran ring. Flavonoids can be classified into various classes, such as flavanones, flavonols, flavones, and others, based on the molecular substitution patterns of their carbon skeletons. It is worth PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19761586 title=View Abstract(s)”>PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19761601 noting that the biological activities and health benefits of the flavonoids are attributed to their potent antioxidant effects in vitro and in vivo. Indeed, we have reported that hydroxylation patterns play a critical role in determining the cellular functions of flavonoids. Recently, we confirmed the anti-influenza virus potency of 3,40 dihydroxyflavone against the influenza A virus in vitro and in vivo. In addition, we recently showed that the transplantation of induced pluripotent stem cells pretreated with 3,20 -dihydroxyflavone into rats with peripheral nerve injury improved axonal regeneration and functional injury recovery in comparison with the control group. Flavonols are a major flavonoid subclass that is characterized by a planar structure with a 3-hydroxyflavone backbone. In recent years, flavonols have been a focus of research due to their important biological activities, such as antioxidant activity and anti-cancer activity. In this study, we compared the antiviral activities of several flavonols and other flavonoids with similar, but distinct, hydroxyl or methyl substitution patterns at the 3, 3′, and 4′ positions of the 15-carbon flavonoid skeleton and f