A class of compounds extracted from plants has shown amazing effects against certain RNA viruses both in a plant and an animal. According to a recent issue of The Proceedings of the National Academy of Sciences, a seco-pregnane steroid is identified by CAS researchers as an effective and selective inhibitor to alpha-virus-like positive-strand RNA viruses, and exert no harm to host cells.
As plants have evolved alternative mechanisms to combat various pathogens with the help of secondary metabolites, it is safe to select the related compounds directly from the plants for new drug agents that are both potentially antiviral and non-toxic to hosts. Although great progresses have been achieved over the past decades on antiviral research and treatment, some of these compounds have been proved to induce the resistance of viruses. The continuing emergency of highly pathogenic syndromes such as the SARS and avian influenza calls for more effective antiviral agents.
Teaming up with researchers from the Chinese Center for Disease Control and Prevention and the Yunnan Academy of Agricultural Sciences, research teams led separately by HAO Xiaojiang from the CAS Kunming Institute of Biology and FANG Rongxiang from the CAS Institute of Microbiology have been successful in screening Strobilanthes cusia and Cynanchum paniculatum, herbs that have long been used in traditional Chinese medicine to treat human infections, to find the active constituents responsible for antiviral activities. They discover that seco-pregnane steroid glaucogenin C and its monosugar-glycoside cynatratoside A extracted from S. cusia, together with three new pantasugar-glycosides of glaucogenin C from C. paniculatum, are able to suppress alpha-virus-like positive-strand RNA viruses, such as the plant-infecting tobacco mosaic virus (TMV), the animal infecting Sindbis virus (SINV), the eastern equine encephalitis virus and the Getah virus. In the process, no toxicity is caused to host cells. Meanwhile, no similar impact has been observed on other RNA or DNA viruses. Additional in vivo experiment shows that the compounds can protect mice from lethal SINV infections without adverse effects on the mice.
Using TMV and SINV as model, the researchers then approached the action mechanism of these antiviral ingredients. It is revealed that they dominantly suppress the expression of viral subgenomic RNA(s) without affecting the accumulation of viral genomic RNA.
The work suggests that the viral subgenomic RNA could be a new target for future antiviral drugs. Also, the seco-pregnane steroid glaucogenin C and its four glycosides extracted from the two medicinal herbs are potential antiviral agents against alpha-virus-like positive-strand RNA viruses.
Effect of paniculatumoside C (3) on TMV spread in N. benthamiana plants. The plants were photographed under long-wave UV light at 5 dpi. Arrows indicate the inoculation sites. [Page]