title: Antiviral effect of theaflavins against caliciviruses.
abstract: Caliciviruses are contagious pathogens of humans and various animals. They are the most common cause of viral gastroenteritis in humans, and can cause lethal diseases in domestic animals such as cats, rabbits and immunocompromised mice. In this study, we conducted cytopathic effect-based screening of 2080 selected compounds from our in-house library to find antiviral compounds against three culturable caliciviruses: feline calicivirus, murine norovirus (MNV) and porcine sapovirus (PoSaV). We identified active six compounds, of which two compounds, both related to theaflavins, showed broad antiviral activities against all three caliciviruses; three compounds (abamectin, a mixture of avermectin B1a and B1b; avermectin B1a; and (-)-epigallocatechin gallate hydrate) were effective against PoSaV only; and a heterocyclic carboxamide derivative (BFTC) specifically inhibited MNV infectivity in cell cultures. Further studies of the antiviral mechanism and structure-activity relationship of theaflavins suggested the following: (1) theaflavins worked before the viral entry step; (2) the effect of theaflavins was time- and concentration-dependent; and (3) the hydroxyl groups of the benzocycloheptenone ring were probably important for the anti-calicivirus activity of theaflavins. Theaflavins could be used for the calicivirus research, and as potential disinfectants and antiviral reagents to prevent and control calicivirus infections in animals and humans.
authors.affiliation: Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.|Department of Pharmaceutical and Food Science, Shizuoka Institute of Environment and Hygiene, Shizuoka, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Ohba
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Oka
authors.affiliation: Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.|Department of Pharmaceutical and Food Science, Shizuoka Institute of Environment and Hygiene, Shizuoka, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ando
authors.affiliation: Department of Microbiology, Shizuoka Institute of Environment and Hygiene, Shizuoka, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Arahata
authors.affiliation: Department of Microbiology, Shizuoka Institute of Environment and Hygiene, Shizuoka, Japan.
authors.forename: Asaka
authors.initials: A
authors.lastname: Ikegaya
authors.affiliation: Division of Biosafety Control and Research, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Takagi
authors.affiliation: Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.|Department of Pharmaceutical and Food Science, Shizuoka Institute of Environment and Hygiene, Shizuoka, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Ogo
authors.affiliation: Department of Veterinary Preventive Medicine, Food Animal Health Research Program, Ohio Agricultural Research and Development Center, College of Veterinary Medicine, The Ohio State University, Wooster, OH, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutical and Food Science, Shizuoka Institute of Environment and Hygiene, Shizuoka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Owada
authors.affiliation: Department of Microbiology, Shizuoka Institute of Environment and Hygiene, Shizuoka, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kawamori
authors.affiliation: Department of Veterinary Preventive Medicine, Food Animal Health Research Program, Ohio Agricultural Research and Development Center, College of Veterinary Medicine, The Ohio State University, Wooster, OH, USA.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Veterinary Preventive Medicine, Food Animal Health Research Program, Ohio Agricultural Research and Development Center, College of Veterinary Medicine, The Ohio State University, Wooster, OH, USA.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Saif
authors.affiliation: Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Asai
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D044946:Biflavonoids / Q000494:pharmacology*; D002139:Caliciviridae / Q000187:drug effects*; D017250:Caliciviridae Infections; D017927:Calicivirus, Feline / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002415:Cats; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005415:Flavins / Q000494:pharmacology*; D006801:Humans; D007559:Ivermectin / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D029322:Norovirus / Q000187:drug effects; D020836:Protein Structure, Quaternary; D029341:Sapovirus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D044946:Biflavonoids; D005415:Flavins; C056068:theaflavin; C048324:abamectin; D007559:Ivermectin; C019264:avermectin; D002392:Catechin; C045651:epigallocatechin gallate