Ningnanmycin inhibits tobacco mosaic virus virulence by binding directly to its coat protein discs

Xiangyang Li,Deyu Hu,Baoan Song,Zhuo Chen,Lu Yu,Qingmin Wang,Gefei Hao,Yan Ding

doi:10.18632/oncotarget.19401

Abstract

Tobacco mosaic virus (TMV) causes severe plant diseases worldwide; however, effective antiviral agents for controlling TMV infections are not available. This lack of effective antiviral agents is mainly due to the poor understanding of potential targets associated with TMV infections. During infection, the coat protein (CP), which is delivered by viral particles into susceptible host cells, provides protection for viral RNA. Here, we found that Ningnanmycin (NNM), a commercially used plant antibacterial agent, inhibits the assembly of the CP by directly binding several residues. These interactions cause the disassembly of the CP from discs into monomers, leading to an almost complete loss of pathogenicity. Substitutions in the involved binding residues resulted in mutants that were significantly less sensitive to NNM. Thus, targeting the binding of viral CPs through small molecular agents offers an effective strategy to study the mechanism of NNM.

Highlights

Plant viral diseases cause significant losses in agriculture and low-cost agents capable of effectively controlling such diseases are in great need
We studied the interactions between NNM and Tobacco mosaic virus (TMV) particles, NNM and coat protein (CP) discs, and TMV RNA and CP discs using microscale thermophoresis (MST) (Figure 1A)
The NNM bound to TMV particles with a dissociation constant (Kd) of 25.8–52.3 μM (Figure 1B and Supplementary Table 1), the NNM bound to CP discs with a Kd of 1.10–3.96 μM (Figure 1C and Supplemental Table 1), and the TMV RNA bound to CP discs with a Kd of 144.8–207.3 μM from 20°C to 30°C (Figure 1D and Supplemental Table 1)

Summary

Introduction

Plant viral diseases cause significant losses in agriculture and low-cost agents capable of effectively controlling such diseases are in great need. Antiviral compounds that target RNA and chemicals that aim at stimulating plant disease resistance have received intensive attention in recent years [1, 2]. Few studies have focused on the use of viral coat proteins (CPs) and their assembly as potential targets for infection control [3]. Tobacco mosaic virus (TMV) causes diseases in a wide variety of economically important plants, yet few effective anti-TMV agents are available [4, 5]. There is a great need to identify novel targets for the development of effective anti-TMV drugs [1,2,3,6]

Methods

Results

Conclusion