New mechanistic insights into the antiviral candidate CA-P: Activation of plant redox-mediated defense and suppression of virus biosynthesis

Abstract

Viral diseases seriously threaten global agriculture, driving the need for new antiviral agents. Currently, viricide development is hindered by limited antiviral agent diversity and unclear mechanisms. Here, we reported that a novel cinnamic acid derivative, CA-P, exhibited strong antiviral activity against Tobacco Mosaic Virus (TMV), with EC₅₀ values of 160.35 mg·L⁻¹ (protective efficacy) and 324.21 mg·L⁻¹ (curative efficacy). It also showed low toxicity to non-target organisms (zebrafish, earthworms, bees, and silkworms). To support the rational design of cinnamic acid-based antiviral molecules and to clarify the relationship between plant defense responses and reactive oxygen species (ROS) regulation, we systematically investigated the mechanism of action of CA-P. Integrated RNA sequencing and biochemical analyses revealed that CA-P modulates redox homeostasis by enhancing the activity of key ROS-scavenging enzymes, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). Simultaneously, CA-P activated a set of ROS-mediated defense responses, such as the mitogen-activated protein kinase (MAPK) signaling cascade, calcium ion flux, hypersensitive response (HR), and systemic acquired resistance via salicylic acid-dependent pathways. These synergistic mechanisms collectively enhance plant resistance against viral infection and environmental stressors. Overall, this study provides innovative insights into the antiviral applications of cinnamic acid derivatives and offers a new perspective on the interplay between defense responses and ROS regulation, thereby facilitating the development of novel plant resistance inducers.