Four new compounds, including three new benzenoids, antrocamphin A (1), antrocamphin B (2), and 2,3,4,5-tetramethoxybenzoyl chloride (3), and a new 1,3-dioxolan-2-one derivative, antrodioxolanone (4), together with 13 known compounds have been isolated from the fruiting body of Antrodia camphorata. The structures of these new compounds were determined through spectral analyses including extensive 2D-NMR data. Among the isolates, antrocamphin A (1), antcin A (10), and antcin B (11) exhibited potent inhibition against fMLP-induced superoxide production with IC50 values less than 10 microM.

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Hydroxychloroquine (HCQ) is an antimalarial drug also used in treating autoimmune diseases. Its antiviral activity was demonstrated in restricting HIV infection in vitro; however, the clinical implications remain controversial. Infection with dengue virus (DENV) is a global public health problem, and we lack an antiviral drug for DENV. Here, we evaluated the anti-DENV potential of treatment with HCQ. Immunofluorescence assays demonstrated that HCQ could inhibit DENV serotype 1-4 infection in vitro. RT-qPCR analysis of HCQtreated cells showed induced expression of interferon (IFN)-related antiviral proteins and certain inflammatory cytokines. Mechanistic study suggested that HCQ activated the innate immune signaling pathways of IFN-b, AP-1, and NFkB. Knocking down mitochondrial antiviral signaling protein (MAVS), inhibiting TANK binding kinase 1 (TBK1)/inhibitor-kB kinase e (IKKe), and blocking type I IFN receptor reduced the efficiency of HCQ against DENV-2 infection. Furthermore, HCQ significantly induced cellular production of reactive oxygen species (ROS), which was involved in the host defense system. Suppression of ROS production attenuated the innate immune activation and anti-DENV-2 effect of HCQ. In summary, HCQ triggers the host defense machinery by inducing ROS-and MAVS-mediated innate immune activation against DENV infection and may be a candidate drug for DENV infection.

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