Medicinal plants in Yunnan Province of China were collected and screened for antiviral activity. Plants that were used to treat diseases that are now known to have viral causes were selected through a systematic survey of information on traditional Chinese medicine and the traditional medicines of ethnic minority groups in the region. Extracts from 31 species in 22 plant families were assayed for inhibition of Sindbis and murine cytomegalovirus infections in mammalian cell cultures. Sixteen of the species showed antiviral activity. Elsholtzia ciliata (Thunb.) Hyland of the mint family (Lamiaceae) showed the highest activity. It has more than one active component and one of them was purified using bioactivity-guided phytochemical fractionation. The compound was identified as the polycyclic aromatic hydrocarbon fluoranthene and its activity was enhanced with exposure to long wavelength ultraviolet radiation. It has not been previously reported to have antiviral activity.;Investigations of the mechanism of action were carried out with the known photosensitive antiviral compound hypercin found in medicinal plants of the genus Hypericum (Hypericaceae). Three hypericin derivatives and five related quinones were tested in structure-activity relationship studies. The new derivative 2,5,9,12-tetra(carboxyethylthiomethyl) hypericin showed potent photosensitive virucidal activity against membrane-enveloped viruses. The photoaction was demonstrated to be of the singlet oxygen type that could be reduced by the presence of a singlet oxygen scavenger. In comparisons of mechanisms of action with that of hypericin in the presence and absence of light, the two compounds showed similar potencies in light but hypericin was more potent in the dark. Examination of the effect of these compounds on Sindbis virus structural proteins showed that treatment with the derivative in light caused an alteration of the capsid protein, an effect that was not shown in treatments with hypericin.
展开▼
