Binding interactions between enantiomeric α-aminophosphonate derivatives and tobacco mosaic virus coat protein

- The binding force of enantiomeric α-aminophosphonate derivatives with TMV CP is R isomer >S isomer.
- Compound Q-Rinteracts with Arg90 of TMV CP through strong hydrogen bonding.
- Substituting arginine with glycine affects the binding affinity of the Q-Rand TMV CP.
- The reassembly TMV R90G virus particle resulted in a loss of its ability to infect tobacco.

Tobacco mosaic virus (TMV) is an important plant virus that can cause considerable crop loss. Our group synthesized a series of enantiomeric α-aminophosphonate derivatives with high anti-TMV activities. The activity of (R)-diphenyl-1-(4-methylbenzothiazole-2-amino)-1-(thiphene-2-yl)-methylphosphonate (Q-R) was found to be superior to that of (S)-diphenyl-1-(4-methyl benzothiazole-2-amino)-1-(thiphene-2-yl)-methylphosphonate (Q-S). However, the mechanism for inhibition of the R-isomer (Q-R) of infection activity is not clear. Thus, we studied the interactions between Q-R and Q-S and TMV by using TMV coat proteins (CP) as a potential target for fluorescence spectroscopy, isothermal titration calorimetry, microscale thermophoresis, and molecular docking. Arg90 was found to play a major role in the interaction of Q-R with TMV CP, as demonstrated by the interaction experiments and the results of molecular modeling. The substitution of arginine with glycine resulted in a mutant that was significantly less sensitive to Q-R. These results indicate that Q-R undermines the structural stability of the TMV R90G virus particle by binding with Arg90, eventually leading to the loss of the virus' ability for infection.