Curcumin loaded poly lactic-co-glycolic acid nanoparticles as an antiviral formulation against Zika virus

DIAZ SIERRA, JOHANNA BRIYITH; DAMONTE, ELSA B.; SEPÚLVEDA, CLAUDIA S.; D´ACCORSO NORMA B.; PUGNI, EUGENIO ; PACHO, NATALIA; GARCÍA, CYBELE C.

Mar del Plata

Congreso; Reunión Conjunta SAIC-SAI-SAFIS 2018; 2018

SAIC-SAI-SAFIS

Antiviral drugs in current use target only viral proteins; are, generally, specific for each type of virus and frequently induce the rapid emergence of resistant mutants, a particularly serious problem for RNA virus therapy due to its high mutation rate. The development of drugs that affect host factors necessary for viral multiplication that involve cellular pathways has proven to be attractive for chemotherapeutic intervention against viruses of the same genus, family and even unrelated, since it is not expected that the individual viral mutations compensate for the loss of a required factor of the host. One mechanism to control rapidly replicating viruses is to manipulate the levels of cellular 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 activities against Chikungunya, Junín, Lassa, several flavivirus members and Ebola viruses. Other authors found that several polyphenols showed inhibitory effect on IMPDH, in particular, curcumin was the more active and exerted a competitive and uncompetitive action to suppress the IMPDH activity. In the present work, the in vitro antiviral effect of curcumin against Zika virus was studied. Firstly, the toxicity was determined for 48 h in monkey Vero cells by de MTT assay. In order to minimize cytotoxicity and maximize the curcumin cell delivery, curcumin loaded poly lactic-co-glycolic acid (PLGA) nanoparticles were synthetized. No cytotoxic effects were observed until 150 µM. Through a viral yield inhibition assay, a dose-dependent viral replication inhibition was observed in a 0-100 µM curcumin concentration range. Our previous reports with other inhibitors and RNA virus, plus these results show that IMPDH is a promissory antiviral target to control pathogenic viral infections and curcumin loaded PLGA nanoparticles may be a good candidate drug formulation.