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Published on: April 24, 2021
Celastrol Suppresses Porcine Deltacoronavirus Replication by Modulating Endoplasmic Reticulum Stress-Associated Ca2+
Jialu Zhang1, Yuqian Liu1, Letao Gao1
1Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China, swu.edu.cn.
Transboundary and Emerging Diseases
|June 29, 2026
Summary
Celastrol (CE) effectively inhibits Porcine deltacoronavirus (PDCoV) replication by regulating endoplasmic reticulum stress and calcium homeostasis. This compound shows promise as a potential therapeutic for PDCoV infections.
Area of Science:
- Virology
- Molecular Biology
- Pharmacology
Background:
- Porcine deltacoronavirus (PDCoV) causes significant economic losses in swine and poses a potential zoonotic risk.
- Current therapeutic options for PDCoV are limited, necessitating the exploration of novel antiviral agents.
Purpose of the Study:
- To investigate the antiviral activity of celastrol (CE), a compound from Tripterygium wilfordii, against PDCoV.
- To elucidate the underlying molecular mechanisms of CE's anti-PDCoV effects, focusing on endoplasmic reticulum (ER) stress and calcium homeostasis.
Main Methods:
- PDCoV replication assays in LLC-PK1 cells treated with varying concentrations of CE.
- Network pharmacology analysis to predict potential pathways involved in CE's mechanism.
- Cellular calcium level measurements and modulation experiments.
- ER stress marker analysis.
- Molecular docking studies to assess CE's interaction with viral proteins.
Main Results:
- CE significantly inhibited PDCoV replication in a dose-dependent manner, affecting multiple viral lifecycle stages.
- CE treatment restored PDCoV-induced calcium accumulation to baseline levels.
- PDCoV infection induced ER stress and altered ER-associated calcium levels, both of which were attenuated by CE.
- Molecular docking suggested CE interacts with multiple PDCoV proteins, indicating a multitarget mechanism.
Conclusions:
- Celastrol demonstrates potent anti-PDCoV activity by modulating ER stress-associated calcium homeostasis.
- CE's multitarget profile suggests its potential as a novel therapeutic agent for PDCoV infections.
- These findings provide crucial insights into host-virus interactions during PDCoV infection and potential therapeutic strategies.
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