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p38 Inhibitor SB203580 Inhibits HEV Infection and Prevents HEV-Related Adverse Pregnancy Outcomes in a Pregnant
Manyu Li1, Wenjun Wan1, Zeyu Song1
1Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, China.
Summary
A novel p38-MAPK inhibitor, SB203580, effectively treats Hepatitis E virus (HEV) infection in pregnant rabbits. This treatment prevents adverse pregnancy outcomes and vertical transmission, offering a safe therapeutic option for HEV during pregnancy.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Hepatitis E virus (HEV) infection in pregnancy causes severe adverse outcomes like stillbirth and maternal death.
- Current treatments (ribavirin, pegylated interferon-α) are contraindicated in pregnant women.
- A safe and effective treatment for HEV infection during pregnancy is critically needed.
Purpose of the Study:
- To investigate the role of the p38-MAPK signaling pathway in HEV replication.
- To evaluate the efficacy and safety of the p38-MAPK inhibitor SB203580 for treating HEV infection during pregnancy.
Main Methods:
- Utilized JEG-3 choriocarcinoma cells to study HEV replication and the p38-MAPK pathway.
- Treated cells with varying concentrations of SB203580 in vitro.
- Validated findings in HEV-infected pregnant rabbits, monitoring viral load, cytokine secretion, apoptosis, and pregnancy outcomes.
Main Results:
- HEV infection altered p38-MAPK pathway expression in JEG-3 cells.
- SB203580 inhibited HEV replication, reduced pro-inflammatory cytokines, and decreased apoptosis in vitro.
- In vivo, SB203580 treatment in pregnant rabbits lowered viral load, reduced placental apoptosis, and prevented adverse pregnancy outcomes and vertical HEV transmission.
Conclusions:
- The p38-MAPK inhibitor SB203580 demonstrates significant efficacy against HEV infection.
- SB203580 is a safe and effective therapeutic candidate for managing HEV infection during pregnancy.
- This study highlights a promising new treatment strategy to improve maternal and fetal health outcomes in HEV-infected pregnancies.
