In vitro antiviral activity of nordihydroguayretic acid and its tetramethylated derivative on Arbovirus with medical-veterinary importance

FLORENCIA MARTINEZ; JAVIER AGUILAR; MARTA SILVIA CONTIGIANI; SUSANA NUÑEZ MONTOYA; BRENDA KONIGHEIM

Mar del Plata

Congreso; Reunión Anual SAIC, SAFE ,SAB y SAP 2019; 2020

Sociedades Argentinas varias

In the search for new antiviral agents from native plant species, we began studying Larrea divaricata CAV. (Zigophyllaceae) and its main metabolite: nordihydroguaiaretic acid (NDGA). The antiviral effect of NDGA and its derivatives has been reported in numerous studies, the range of viruses evaluated is wide. However, there are few reports on arboviruses. We aimed to evaluate the in vitro effect of NDGA and its tetra methylated derivative, NDGA-4-M, on arbovirus: Chikungunya (CHIKV), St. Louis encephalitis (SLEV), Bunyamwera (BUNV) and Dengue types 1 and 4 (DENV-1, DENV-4), trying to establish the stages of the viral replication cycle affected. Cytotoxicity was assessed as a measure of the host cell viability in vitro by the neutral red uptake method. The virucidal and antiviral effects were evaluated by the plaque forming units (PFU) method. To those compounds showing active, we studied their action in several stages of the viral replication cycle, by using the UFP reduction method at different treatment times. Concentration of NDGA and NDGA-4-M causing 50 % of cytotoxicity (CC50) in LLC-MK2 cells were 115.7 µM and 7.8 µM respectively. NDGA-4-M was not able to inhibit any of the viruses tested. Although NDGA was not active also on CHIKV, SLEV and DENV-4, it was active on DENV-1 and BUNV with a selectivity index of 8.4 and 5.2 respectively. NDGA also produced an inhibition greater than 3 logarithms on DENV-1 when assessing virucidal activity. When evaluating the NDGA effect at different times of the viral replication cycle, it was determined that NDGA acts during the first two hours post-internalization (p.i.) on DENV-1 infection. By contrast, it was active all the time p.i. viral of the BUNV and, to a lesser extent, when cells were pre-treated before infection. Since there is currently no specific antiviral therapy available for the effective clinical treatment of infections produced by arboviruses, these results make NDGA a promising drug to treat these infections.