Antiviral activity of curcumin, a natural polyphenolic compound, for Junin and Zika viruses

PUGNI, EUGENIO; DIAZ SIERRA, JB; SCOLARO LA; WAGNER, MS; SEPÚLVEDA CS; GARCÍA CC; WAINSTEIN, DC; DAMONTE EB

Buenos Aires

Congreso; Drug Discovery for Neglected Diseases International Congress 2018 4th Scientific Meeting of ResNet NPND; 2018

ResNet NPND

The development of drugs that affect host factors necessary for viral multiplication has proven to be attractive for chemotherapeutic intervention. In this line, a mechanism to control rapidly replicating viruses is to manipulate the levels of nucleoside triphosphate pools. Inosine-5′-monophosphate dehydrogenase (IMPDH) is an enzyme involved in the de novo synthesis of guanine nucleotides. Inhibitors of IMPDH such as ribavirin, mycophenolic acid and merimepodib have shown antiviral activities against several viruses. Other authors found that polyphenols showed inhibitory effect on IMPDH, being curcumin, a natural compound obtained from Curcuma longa plant, the more active to suppress IMPDH activity. In the present work, the in vitro antiviral effect of curcumin against Junin arenavirus and Zika flavivirus was studied. The former being the causative agent of the argentine hemorrhagic fever, a severe zoonotic disease of the central area of Argentina, and the latter being en emerging pathogen of worldwide distribution. Materials and methods:Cytotoxic concentration (CC50) of the drug was determined in Vero cells by MTT method or by staining with crystal violet of cell monolayers subjected to different concentrations of the drug for 48 h. Inhibitory effect of curcumin was determined by a yield assay of infectivity in supernatants of infected cells. Synthesis of JUNV nucleoprotein (N) was analysedby WB at 4 days p.i. in cultures untreated or treated under different conditions. Virucidal activity assay for JUNV was carried out by quantifying survival infectivity after subjecting a viral stock dilution that contains 10000 PFU to different concentrations of the drug for 1 hour at 37ºC.Results:A CC50% of 80 μM and >150 µM, for crystal violet and MTT, respectively, was determined after a 48-hour treatment. A reduction of approx. 30% of virus yield was detected in JUNV infected cells treated with curcumin (40 µM) which correlated with a decrement in intensity of the cytopathic effect caused by the virus and a decrease in the expression of the viral nucleoprotein. The virucidal activity assay for JUNV showed that survival infectivity was 26 and 20% for concentrations of 160 and 320μM curcumin, respectively. No effect was detected when concentrations ranged between 5 and 80 μM.In the case of ZIKV, a dose-dependent viral replication inhibition was observed in a 0-100 µM curcumin concentration range. Conclusions:These results show that curcumin inhibits JUNV and ZIKV in vitro multiplication and that IMPDH would be a promissory antiviral target to control pathogenic viral infections.[1] Mounce BC et al. Antiviral Res. 2017 Jun; 142:148-157Financial support: This research was supported by Agencia Nacional dePromociónCientífica y Tecnológica (ANPCyT), Universidad de Buenos Aires (UBA) and CONICET.