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

Abstract

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 <b>9k</b>, <b>12b</b>, and <b>12d</b> displayed about similar inhibitory effects as ningnanmycin (inhibitory rates of 55, 57, and 59% at 500 μg/mL for inactivation, curative, and protection activities <i>in vivo</i>, respectively), the best antiviral agent at present, and emerged as novel antiviral leads for further research. We selected <b>9k</b> for further antiviral mechanism research <i>via</i> transmission electron microscopy and molecular docking, which revealed that compound <b>9k</b> 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 <b>14</b> with a 100% antifungal effect against <i>Botrytis cinereal</i> emerged as a lead for further research. This work provides a reference for the development of agricultural active ingredients based on Chinese medicine plants.