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Structure–activity relationship analysis of curcumin analogues on anti‐influenza virus activity
Author(s) -
Ou JunLin,
Mizushina Yoshiyuki,
Wang ShengYang,
Chuang DuenYau,
Nadar Muthukumar,
Hsu WeiLi
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12503
Subject(s) - curcumin , chemistry , docking (animal) , influenza a virus , structure–activity relationship , pharmacology , virus , stereochemistry , biochemistry , virology , biology , in vitro , medicine , nursing
Curcumin ( C ur) is a commonly used colouring agent and spice in food. Previously, we reported that C ur inhibits type A influenza virus ( IAV ) infection by interfering with viral haemagglutination ( HA ) activity. To search for a stable Cur analogue with potent anti‐ IAV activity and to investigate the structure contributing to its anti‐ IAV activity, a comparative analysis of structural and functional analogues of Cur, such as tetrahydrocurcumin ( THC ) and petasiphenol (Pet), was performed. The result of time‐of‐drug addition tests indicated that these curcuminoids were able to inhibit IAV production in cell cultures. Noticeably, Pet and THC inhibit IAV to a lesser extent than Cur, which is in line with their effect on reducing plaque formation when IAV was treated with Cur analogues before infection. Unexpectedly, both THC and Pet did not harbour any HA inhibitory effect. It should be noted that the structure of Pet and THC differs from Cur with respect to the number of double bonds present in the central seven‐carbon chain, and structure modelling of Cur analogues indicates that the conformations of THC and Pet are distinct from that of Cur. Moreover, simulation docking of Cur with the HA structure revealed that Cur binds to the region constituting sialic acid anchoring residues, supporting the results obtained by the inhibition of HA activity assay. Collectively, structure–activity relationship analyses indicate that the presence of the double bonds in the central seven‐carbon chain enhanced the Cur ‐dependent anti‐ IAV activity and also that Cur might interfere with IAV entry by its interaction with the receptor binding region of viral HA protein.