Synthesis of Four Optical Isomers of Antiviral Agent NK0209 and Determination of Their Configurations and Activities against a Plant Virus

Abstract

Previously, we reported for the first time that harmala alkaloids harmine and tetrahydroharmine exhibit activity against plant viruses, and we developed an analogue, designated NK0209, that efficiently prevents and controls plant virus diseases. Here, to investigate the influence of the spatial configuration of NK0209 on its antiviral activities, we synthesized its four optical isomers, determined their configurations, and evaluated their activities against tobacco mosaic virus. All four isomers were significantly more active than ningnanmycin, which is one of the most successful commercial antiviral agents, with in vivo inactivation, cure, and protection rates of 57.3 ± 1.9, 54.2 ± 3.3, and 55.0 ± 4.1% at 500 μg/mL. Furthermore, analysis of structure–activity relationships demonstrated for the first time that the spatial conformation of NK0209 is an important determinant of its antiviral activity, and our results provide information about the possible optimum configuration for interaction of this molecule with its target protein.

Recent Achievements in Antiviral Agent Development for Plant Protection

“…In 2020, Song and co-workers 111 reported that all the four isomers of the antiplant virus drug NK0209 are effective in the prevention and control of the diseases caused by plant viruses. All the four isomers of the NK0209 were independently synthesized and the effects of them on antiviral activities against TMV were studied.…”

Recent Research Progress: Discovery of Anti-Plant Virus Agents Based on Natural Scaffold

“…The anti-TMV inactivating, curative, and protective activities of compound 48 were 59, 63 and 60% at 500 mg/L, respectively ( Huang et al, 2018 ). Compound 49 showed excellent inactivating, curative, and protective activities against TMV with EC 50 values of 127, 156, and 108 mg/L, respectively ( Wang and Song, 2020c ). Compound 50 not only retarded TMV proliferation, but also had a concentration-dependent effect on tobacco growth and biomass accumulation ( Zhang X. et al, 2021 ).…”

Characterization, Chemistry, Structural Activity Relationship and Antimicrobial Activities of Tetrahydro-β-carboline

“…Additionally, (19) shown fungicidal effects against Cercospora arachidicola Hori, Alternaria solani, Bipolaris maydis, and Rhizoctonia solani [28] . On the basis of compound (11), further compounds (12) For the total prevention and control of TMV viral disease in the field, NK0209 was the first drug to be successful [27] .…”