Structure–activity relationship analysis of curcumin analogues on anti‐influenza virus activity

Abstract

Curcumin (Cur) is a commonly used colouring agent and spice in food. Previously, we reported that Cur 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.

Utilising polyphenols for the clinical management of Candida albicans biofilms

“…Compared with PYG (containing only one phenol group in its structure), CUR has two phenol groups connected by two ,-unsaturated carbonyl groups. In addition, the presence of two unsaturated double bonds in the central connecting chain may further potentiate its activity [13], although further studies are required to elucidate the precise mechanism. Notably, downregulation of key biofilm genes, such as the adhesin als3 and the hyphal protein hwp1, explains the impeded biofilm phenotype.…”

Curcumin Differs from Tetrahydrocurcumin for Molecular Targets, Signaling Pathways and Cellular Responses

“…•Curcumin inhibited type A influenza virus infection to a greater extent than THC by interfering with viral hemagglutination activity [45].…”

“…Curcumin has been reported to inhibit type A influenza virus (IAV) infection by interfering with viral hemagglutination (HA) activity [54,55], whereas THC has been less effective for suppression of IAV infection [45]. Further studies indicated that curcumin, but not THC, harbors the HA inhibitory effect.…”

3D-quantitative structure–activity relationship and antiviral effects of curcumin derivatives as potent inhibitors of influenza H1N1 neuraminidase

“…In particular, curcumin is reported to have anti-influenza virus activity by interfering with the cellular signaling pathways (such as Toll-like receptor2/4, p38/c-Jun N-terminal kinase, mitogen-activated protein kinase, and nuclear factor-κB pathways) or with proteins required for influenza virus replication (Dai et al 2018;Richart et al 2018). Ou et al (2013) reported that the presence of the double bonds in the central seven-carbon chain enhances the curcumin-dependent anti-IAV activity and curcumin might interfere with IAV entry by its interaction with the receptor binding region of hemagglutinin. Chen et al (2013) also reported that curcumin can inhibit influenza virus by disrupting integrity of the viral envelope and liposomal membranes.…”