Ginkgolic acid inhibits the replication of pseudorabies virus in vitro and in vivo by suppressing the transcription of viral late genes

by Selleckchem | Nov 22 2023

Pseudorabies virus (PRV) belongs to the species of alphaherpesvirus that can cause substantial economic losses to the world swine industry. Therefore, research on anti-PRV compounds is of great value. In this study, it was found that ginkgolic acid could efficiently inhibit the replication of PRV, and the IC50 and CC50 were 3.407 μM and 102.3 μM, respectively. Moreover, it was discovered that ginkgolic acid had no effect on the adsorption, entry, and release stages of the PRV replication cycle. Importantly, it was found that ginkgolic acid could significantly suppress the transcription of PRV late genes, while the transcription of viral immediate early and early genes was not affected. Finally, in vivo experiments showed that ginkgolic acid could significantly reduce the viral load of PRV in multiple tissues and increase 30% survival rate of mice upon the challenge of PRV. Taken together, a novel PRV replication inhibitor, ginkgolic acid, which worked through suppressing the transcription of the late genes, was found in this study. This study provides a potential therapy method for the infection of PRV.

Comments:

The research findings you've described demonstrate the potential of ginkgolic acid as a promising anti-pseudorabies virus (PRV) compound. The study reveals several important aspects of ginkgolic acid's inhibitory effects on PRV replication:

1. **Inhibition of Replication:** Ginkgolic acid efficiently inhibits PRV replication with an IC50 (half-maximal inhibitory concentration) of 3.407 μM, indicating its potency in inhibiting the virus.

2. **Specific Targeting:** Ginkgolic acid appears to specifically target the transcription of PRV late genes. This specificity is valuable, as it suggests that the compound disrupts a specific stage of the virus replication cycle, making it a targeted and potentially effective treatment.

3. **In Vivo Efficacy:** In vivo experiments demonstrate the effectiveness of ginkgolic acid in reducing the viral load of PRV in multiple tissues. Additionally, the compound increases the survival rate of mice by 30% when they are challenged with PRV. This indicates not only the potential therapeutic application but also the practical viability of ginkgolic acid in combating PRV infections.

4. **Mechanism of Action:** The study provides insights into the mechanism through which ginkgolic acid operates. By suppressing the transcription of PRV late genes, it interferes with the virus's ability to replicate and spread, thereby reducing its impact on the host.

5. **Potential Therapeutic Implications:** The findings offer a new approach for developing therapies against PRV infections. Understanding the specific stage of the virus life cycle that ginkgolic acid targets (transcription of late genes) could aid in the development of more targeted antiviral drugs in the future.

In summary, this study highlights ginkgolic acid as a novel inhibitor of PRV replication, shedding light on its specific mode of action and its potential as a therapeutic agent. Further research and development based on these findings could lead to the creation of effective treatments for PRV infections, benefiting the swine industry and potentially other fields dealing with related alphaherpesviruses.