Antiviral activity and mechanism of gossypols: effects of the O2˙− production rate and the chirality

Abstract

(−)-Gossypol displayed an obviously higher antiviral activity against the tobacco mosaic virus (TMV) than (+)-gossypol, whereas the anti-TMV activity of (−)-gossypol Schiff bases is not significantly higher than (+)-gossypol Schiff bases. A mechanism study indicated that these gossypol compounds could neither inhibit the multiplication of TMV nor induce the systemic acquired resistance of tobacco plants. However, gossypol compounds with high anti-TMV activities could induce the accumulation of reactive oxygen species (ROS) in tobacco leaves, and this result is in accordance with the characteristics of extreme resistance featuring a necessary early and rapid ROS (O₂˙⁻ or H₂O₂) accumulation in plants. Further study showed that, the anti-TMV activities of the test compounds decreased synchronously when the O₂˙⁻ accumulation was reduced by superoxide dismutase (SOD). However, when the H₂O₂ accumulation was suppressed by hydrogen peroxidase (CAT), the anti-TMV activities did not change. Therefore, compared with the H₂O₂ accumulation in gossypol compounds-treated tobacco leaves, the O₂˙⁻ accumulation is a key factor for the development of the anti-TMV activities of those compounds, and their anti-TMV mechanism belonged to their extreme resistance. Further study showed that the O₂˙⁻ accumulation in the (−)-gossypol-treated tobacco leaves was mainly from the tobacco itself, whereas the same O₂˙⁻ accumulation in the gossypol Schiff base-treated tobacco leaves was at least partially related to the O₂˙⁻ produced by the compound. Accordingly, gossypol compounds achieved their anti-TMV activities by stimulating O₂˙⁻ accumulation in the tobacco, which was induced either by the O₂˙⁻ production or by the chirality of the gossypol compounds, and this result could also explain why (−)-gossypol or gossypol Schiff bases displayed higher anti-TMV activities than (+)-gossypol.