Differential antiviral activity of some IMPDH inhibitors

Chemical procedures, one of the experimental approaches for restoring to health parts of infected plants, have been evaluated for their ability to interfere with virus replication in host tissue. Few chemicals have been found to eliminate or reduce replication of phytoviruses as compared to the broad selections of therapeutic chemicals available against human viruses. With regard to inhibitors of the inosine monophosphate dehydrogenase (IMPDH) group, two types of compounds endowed with antiviral activity have been discovered: synthetic nucleoside inhibitors, as Tiazofurin (2-β-D-ribofuranosylthiazole-4-carboxamide), Benzamide-Riboside [3-(1-deoxy-β-D-ribofuranosyl)benzamide] and non-nucleoside inhibitors, as Mycophenolic-acid (6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methyl-hex-4-enoic acid). One of our projects carried out to investigate the antiviral activity of several IMPDH inhibitors was designed to verify their action on an in vitro system (explants of Nicotiana tabacum cv Xanthi infected by Cucumber Mosaic Virus) developed as a rapid technique to identify suitable compounds against plant viruses. The appropriate drug concentration was evaluated by preliminary screening on healthy explants. ELISA and biological assays were used to identify the sanitary conditions of treated explants after each therapeutic cycle. After healing treatments, ELISA-negative explants were follewed by biological assays on in vivo N. benthamiana plants. At the end, ELISA readings and biological assays showed 66.6%, 60.0 % and 27.2 % non-infected explants following Mycophenolic-acid, Benzamide-Riboside and Tiazofurin treatment respectively. We also tested drugs against Tobacco Mosaic Virus infection, but no eradication was achieved by any drugs . Our results thus represent a starting point for an in-depth analysis of the potential action of IMPDH inhibitors against phytoviruses as well.