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Blebbistatin as a novel antiviral agent targeting equid herpesvirus type 8.
Abstract: Equid herpesvirus type 8 (EqHV-8) poses a significant threat to equine health, leading to miscarriages and respiratory diseases in horses and donkeys, and results in substantial economic losses in the donkey industry. Currently, there are no effective drugs or vaccines available for EqHV-8 infection control. Unassigned: In this study, we investigated the and antiviral efficacy of Blebbistatin, a myosin II ATPase inhibitor, against EqHV-8. Unassigned: Our results demonstrated that Blebbistatin significantly inhibited EqHV-8 infection in Rabbit kidney (RK-13) and Madin-Darby Bovine Kidney (MDBK) cells in a concentration-dependent manner. Notably, Blebbistatin was found to disrupt EqHV-8 infection at the entry stage by modulating myosin II ATPase activity. Moreover, experiments revealed that Blebbistatin effectively reduced EqHV-8 replication and mitigated lung pathology in a mouse model. Unassigned: Collectively, these findings suggest that Blebbistatin holds considerable potential as an antiviral agent for the control of EqHV-8 infection, presenting a novel approach to addressing this veterinary challenge.
Copyright © 2024 Li, Cui, Yu, Sun, Li, Li, Li, Chen, Khan, Wang and Wang.
Publication Date: 2024-06-05 PubMed ID: 38898998PubMed Central: PMC11186319DOI: 10.3389/fvets.2024.1390304Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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Blebbistatin shows promise as a new antiviral treatment by inhibiting equid herpesvirus type 8 (EqHV-8), which affects horses and donkeys and currently lacks effective therapies. This study demonstrates that Blebbistatin disrupts virus entry and replication, reducing disease symptoms in laboratory cell cultures and animal models.
Background and Significance
- EqHV-8 is a virus causing significant health issues in equines, particularly horses and donkeys.
- Infection leads to miscarriages and respiratory diseases, severely impacting animal welfare and the donkey industry economically.
- There are currently no approved drugs or vaccines for preventing or treating EqHV-8 infections.
- A need exists for novel antiviral strategies to manage this veterinary threat.
Therapeutic Candidate: Blebbistatin
- Blebbistatin is a chemical compound known as a myosin II ATPase inhibitor.
- Myosin II ATPase is involved in cellular processes including cytoskeleton dynamics, which can influence virus entry and replication.
- This study hypothesized that inhibiting myosin II ATPase with Blebbistatin could block EqHV-8 infection.
Experimental Methods
- Cell culture assays were conducted using Rabbit Kidney (RK-13) and Madin-Darby Bovine Kidney (MDBK) cell lines to test antiviral activity in vitro.
- Various concentrations of Blebbistatin were applied to evaluate dose-dependent antiviral effects.
- Mechanistic studies focused on determining the stage of viral infection impacted by Blebbistatin, particularly viral entry.
- Animal experiments involved a mouse model to assess in vivo effectiveness, including monitoring viral replication and lung pathology.
Key Findings
- Blebbistatin significantly inhibited EqHV-8 infection in both RK-13 and MDBK cells in a concentration-dependent manner.
- The drug disrupted the viral infection primarily during the entry phase by modulating cellular myosin II ATPase activity, which is crucial for virus internalization.
- In mice, treatment with Blebbistatin reduced EqHV-8 replication levels in tissues.
- Mice treated with Blebbistatin showed reduced lung pathology compared to untreated controls, indicating therapeutic benefit.
Implications and Future Directions
- The study identifies Blebbistatin as a promising antiviral agent targeting EqHV-8 infection through host cell mechanisms.
- This approach offers a novel strategy distinct from traditional antiviral drugs that target viral proteins directly.
- Further research is needed to evaluate safety, dosing, and efficacy in larger equine populations before clinical application.
- Development of Blebbistatin derivatives with optimized pharmacological properties might improve usability in veterinary medicine.
- Ultimately, this research could lead to effective treatments that reduce economic losses and improve equid health worldwide.
Cite This Article
APA
Li L, Cui X, Yu Y, Sun Q, Li W, Li Y, Li S, Chen L, Khan MZ, Wang C, Wang T.
(2024).
Blebbistatin as a novel antiviral agent targeting equid herpesvirus type 8.
Front Vet Sci, 11, 1390304.
https://doi.org/10.3389/fvets.2024.1390304 Publication
Researcher Affiliations
- College of Agronomy, Liaocheng University, Liaocheng, China.
- College of Agronomy, Liaocheng University, Liaocheng, China.
- College of Agronomy, Liaocheng University, Liaocheng, China.
- College of Agronomy, Liaocheng University, Liaocheng, China.
- College of Agronomy, Liaocheng University, Liaocheng, China.
- College of Agronomy, Liaocheng University, Liaocheng, China.
- College of Agronomy, Liaocheng University, Liaocheng, China.
- College of Agronomy, Liaocheng University, Liaocheng, China.
- College of Agronomy, Liaocheng University, Liaocheng, China.
- College of Agronomy, Liaocheng University, Liaocheng, China.
- College of Agronomy, Liaocheng University, Liaocheng, China.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Citations
This article has been cited 5 times.- Yue W, Yang Y, Miao Y, Li J, Li S, Yang Y, Zhang Y, Qian B, Li Y, Gu H. Optimizing the Method for Differentiation of Functional Platelets from Human Induced Pluripotent Stem Cells. Stem Cell Rev Rep 2026 Apr;22(3):1325-1340.
- Ullah A, Khan MZ, Wang C. Overview of Donkey Welfare and Husbandry Practices in Asia. Animals (Basel) 2025 Dec 1;15(23).
- Khan MZ, Li Y, Zhu M, Li M, Wang T, Zhang Z, Liu W, Ma Q, Wang C. Advances in Donkey Disease Surveillance and Microbiome Characterization in China. Microorganisms 2025 Mar 26;13(4).
- Yu Y, Wang J, Ruan L, Chen L, Khan MZ, You A, Wang C, Li L, Ren H, Wang T, Liu W. Evaluation of Celastrol Antiviral Activity Against Equid Alphaherpesvirus Type 8 Infection. Viruses 2025 Feb 28;17(3).
- Ruan L, Li L, Yang R, You A, Khan MZ, Yu Y, Chen L, Li Y, Liu G, Wang C, Wang T. Equine Herpesvirus-1 Induced Respiratory Disease in Dezhou Donkey Foals: Case Study from China, 2024. Vet Sci 2025 Jan 14;12(1).
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