Biological evaluation of anti-influenza viral activity of semi-synthetic catechin derivatives

• Published in: Antiviral research 2007-11, Vol.76 (2), p.178-185
• Main Authors: Song, Jae Min, Park, Ki Duk, Lee, Kwang Hee, Byun, Young Ho, Park, Ju Hee, Kim, Sung Han, Kim, Jae Hong, Seong, Baik Lin
• Format: Article
• Language: English
• Subjects: Alkyl chain; Amantadine - pharmacology; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Avian influenza virus; Biological and medical sciences; Catechin - analogs & derivatives; Catechin - chemical synthesis; Catechin - chemistry; Catechin - pharmacology; Catechin derivatives; Cell Line; Chickens; Dogs; Drug Evaluation, Preclinical; Eggs - virology; Hemagglutination Inhibition Tests; Hemagglutinin; Human viral diseases; Infectious diseases; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H2N2 Subtype - drug effects; Influenza A Virus, H3N2 Subtype - drug effects; Influenza A Virus, H9N2 Subtype - drug effects; Influenza B virus - drug effects; Influenza virus; Medical sciences; Molecular Structure; Oseltamivir - pharmacology; Pharmacology. Drug treatments; Structure-Activity Relationship; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Viral Plaque Assay; Virus Attachment - drug effects; Virus Internalization - drug effects; Virus Replication - drug effects
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2007.07.001

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 μM 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.