Luotonin A and Its Derivatives as Novel Antiviral and Antiphytopathogenic Fungus Agents

Plant diseases caused by viruses and fungi have posed a serious threat to global agricultural production. The discovery of new leads based on Natural Products is an important way to innovate pesticides. In this work, natural product luotonin A was found to have good Antiviral activity against tobacco mosaic virus (TMV) for the first time. A series of luotonin A derivatives were designed, synthesized, and evaluated for their Antiviral activities and fungicidal activities systematically. Most compounds displayed better Antiviral activities against TMV than commercial ribavirin. Compounds 9k, 12b, and 12d displayed about similar inhibitory effects as ningnanmycin (inhibitory rates of 55, 57, and 59% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively), the best Antiviral agent at present, and emerged as novel Antiviral leads for further research. We selected 9k for further Antiviral mechanism research via transmission electron microscopy and molecular docking, which revealed that compound 9k can interact with TMV coat protein through the hydrogen bond, leading to its polymerization, thus preventing virus assembly. Further fungicidal activity tests showed that these compounds also showed broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi. Especially, compound 14 with a 100% Antifungal effect against Botrytis cinereal emerged as a lead for further research. This work provides a reference for the development of agricultural active ingredients based on Chinese medicine Plants.

antiviral activity; fungicidal activity; lead discovery; luotonin A; mode of action; structure optimization.