Biological evaluation of anti-influenza viral activity of semi-synthetic catechin derivatives.
Catechin derivatives with different alkyl chain length and aromatic ring substitutions at the 3-hydroxyl group were synthesized from epigallocatechin (EGC) and (+)-catechin (C) and their anti-influenza viral activity were evaluated in vitro and in ovo. Pronounced antiviral activity was observed for derivatives carrying moderate chain length (7-9 carbons) as compared to those with aromatic rings, whereas the 5'-hydroxyl group of the trihydroxy benzyl moiety did not significantly contribute to antiviral activity. The derivatives exerted inhibitory effects for all six influenza subtypes tested including three major types of currently circulating human influenza viruses (A/H1N1, A/H3N2 and B type), H2N2 and H9N2 avian influenza virus. The compounds strongly inhibited adsorption of the viruses on red blood cell (RBC). They also restricted the growth of avian influenza virus in ovo with minimum inhibition concentration (MIC) of 5-10 microM far exceeding the neuraminidase (NA) inhibitor oseltamivir or M2 proton channel inhibitor amantadine. The antiviral activity appears to be mediated by interaction with hemagglutinin (HA)/viral membrane rendering HA less fusogenic at the initial stage of infection. The broad spectrum activity against various subtypes of influenza viruses may complement the limitations of current antivirals and contribute for managing potentially emerging influenza pandemic. The structure-activity data of catechin derivatives may usefully guideline future research endeavors for applying green tea catechins as alternative anti-viral agents.
Song
Jae Min
JM
Department of Biotechnology, College of Engineering, Yonsei University, Seoul, South Korea.
Park
Ki Duk
KD
Lee
Kwang Hee
KH
Byun
Young Ho
YH
Park
Ju Hee
JH
Kim
Sung Han
SH
Kim
Jae Hong
JH
Seong
Baik Lin
BL
D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002645:Chickens; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004531:Eggs / Q000821:virology; D006385:Hemagglutination Inhibition Tests; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D053121:Influenza A Virus, H2N2 Subtype / Q000187:drug effects*; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects*; D053127:Influenza A Virus, H9N2 Subtype / Q000187:drug effects*; D009981:Influenza B virus / Q000187:drug effects*; D015394:Molecular Structure; D053139:Oseltamivir / Q000494:pharmacology; D013329:Structure-Activity Relationship; D010948:Viral Plaque Assay; D053585:Virus Attachment / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D053139:Oseltamivir; D002392:Catechin; D000547:Amantadine