Anti-dengue virus activity of natural podocarpane-type diterpenoid in vitro / 药学学报

ABSTRACT

Dengue virus (DENV) is the most rapidly transmitted mosquito-borne pathogen, which is the main cause of seasonal outbreaks of dengue fever and dengue hemorrhagic fever in tropical and subtropical regions, and may cause serious life-threatening diseases. There is an urgent need to develop effective vaccines or antiviral therapies. In this paper, we found that a podocarpane-type diterpenoid, (3α,5β,10α)-13-methoxypodocarpa-8,11,13-triene-3,12-diol (MPTD), isolated from the stems and leaves of Aleurites moluccana, showed good effect against DENV. The anti-DENV activity of MPTD against four different DENV serotypes was studied by plaque assay. The cytotoxicity of MPTD in Vero and Huh7 cells was tested by MTT assay. qRT-PCR and Western blot assays were used to investigate the anti-DENV activity of MPTD at RNA and protein levels, respectively. The results showed that MPTD greatly reduced the virus titer in DENV infected Vero cells, and its 50% effective concentration (EC50) for DENV (1–4) were 2.72 ± 0.39, 10.99 ± 5.18, 18.72 ± 0.21, and 0.48 ± 0.28 μmol·L-1, respectively. The results showed that MPTD inhibits DENV RNA level and the expression of E protein. In addition, MPTD may inhibit the early stage of DENV replication and exert antiviral activity. Further studies showed that the inhibitory effect of MPTD against DENV infection is not targeting the viral entry stage. Therefore, MPTD has a significant anti-dengue virus effect, and is an anti-DENV compound with potential application value.