image: Molecular mechanism diagram of RG7388 inhibiting SFTSV
Credit: ©Science China Press
Researchers from Professor Wang Tao's team at the School of Life Sciences, Tianjin University, have recently offered fresh insights into how Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV), an emerging tick-borne pathogen, opposes host apoptosis signaling. Based on these findings, they have identified the anticancer drug RG7388 (Idasanutlin) as exhibiting promising antiviral activity against SFTSV.
SFTSV, which lacks any clinically approved specific treatment or vaccine, poses a significant public health threat due to its high mortality rate. The virus is spreading rapidly across broader regions in China, particularly through tick vectors and migratory bird populations, thereby posing a risk not only in Asia but also beyond.
As the corresponding author of the study published in Science Bulletin and Vice Dean of the School of Life Sciences at Tianjin University, Professor Wang Tao has been a dedicated researcher exploring the interaction mechanism between SFTSV and its hosts. His work has contributed to the ongoing advancement of antiviral treatment strategies.
Acknowledging the pressing need for an anti-SFTSV drug, Professor Wang Tao noted that the mortality rate among elderly patients and those with underlying medical conditions remains high. He emphasized the need for continued efforts in the development and clinical application of an effective antiviral agent.
The study focused on the unresolved issue of how mitochondrial damage induced by SFTSV infection relates to the antagonism of apoptosis. Previous research has indicated that SFTSV infection triggers the release of apoptotic factors from mitochondria, yet apoptosis itself has never been observed. Leveraging a wealth of omics data accumulated by the research group, Professor Wang Tao's team found that SFTSV downregulates p53 in an MDM2-dependent manner, leading to the transcriptional inhibition of the p53 target gene Apaf-1. This significantly impedes the assembly of apoptotic complexes.
With this understanding of the molecular mechanism, the research team utilized the MDM2 inhibitor RG7388 to enhance cells' sensitivity to apoptotic stimulation signals. The result was that cells died in the early stages of infection, effectively inhibiting virus replication.
Professor Wang Tao pointed out that RG7388, an anticancer drug currently in Phase III clinical trials, has demonstrated a favorable safety profile. While further development is needed before it can be clinically approved for antiviral use, the research findings have opened up new possibilities for the therapeutic potential of this compound in antiviral therapy.
This new understanding marks a step towards addressing the challenge posed by SFTSV and other tick-borne viruses, offering potential hope for patients and public health officials.