title: Antiviral effect of methylated flavonol isorhamnetin against influenza.
abstract: Influenza is an infectious respiratory disease with frequent seasonal epidemics that causes a high rate of mortality and morbidity in humans, poultry, and animals. Influenza is a serious economic concern due to the costly countermeasures it necessitates. 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 found that the strongest antiviral effect was induced by isorhamnetin. Similar to quercetin and kaempferol, isorhamnetin possesses a hydroxyl group on the C ring, but it has a 3'-methyl group on the B ring that is absent in quercetin and kaempferol. Co-treatment and pre-treatment with isorhamnetin produced a strong antiviral effect against the influenza virus A/PR/08/34(H1N1). However, isorhamnetin showed the most potent antiviral potency when administered after viral exposure (post-treatment method) in vitro. Isorhamnetin treatment reduced virus-induced ROS generation and blocked cytoplasmic lysosome acidification and the lipidation of microtubule associated protein1 light chain 3-B (LC3B). Oral administration of isorhamnetin in mice infected with the influenza A virus significantly decreased lung virus titer by 2 folds, increased the survival rate which ranged from 70-80%, and decreased body weight loss by 25%. In addition, isorhamnetin decreased the virus titer in ovo using embryonated chicken eggs. The structure-activity relationship (SAR) of isorhamnetin could explain its strong anti-influenza virus potency; the methyl group located on the B ring of isorhamnetin may contribute to its strong antiviral potency against influenza virus in comparison with other flavonoids.
authors: Department of Animal Biotechnology, Animal Resources Research Center, and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Gwangjin-Gu, Seoul, Republic of Korea.
authors: Ahmed
authors: A
authors: Abdal Dayem
authors: Department of Animal Biotechnology, Animal Resources Research Center, and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Gwangjin-Gu, Seoul, Republic of Korea.
authors: Hye Yeon
authors: HY
authors: Choi
authors: Department of Bio-Industrial Technologies, Konkuk University, Gwangjin-Gu, Seoul, Republic of Korea.
authors: Young Bong
authors: YB
authors: Kim
authors: Department of Animal Biotechnology, Animal Resources Research Center, and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Gwangjin-Gu, Seoul, Republic of Korea.
authors: Ssang-Goo
authors: SG
authors: Cho
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002645:Chickens / Q000821:virology; D004285:Dogs; D004531:Eggs / Q000821:virology; D005260:Female; D044948:Flavonols / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D015996:Survival Rate; D019562:Viral Load / Q000379:methods
chemical_list: D000998:Antiviral Agents; D044948:Flavonols; C047368:3-methylquercetin; D011794:Quercetin