Chinese Scientists Explore New Monkeypox Therapeutic Targets and Drug Repurposing Strategies
Nikhil Prasad Fact checked by:Thailand Medical News Team Dec 09, 2024 2 days, 21 hours, 33 minutes ago
Medical News: Monkeypox (Mpox), a viral disease that resurfaced in global prominence in 2022, has sparked significant concern worldwide. Originally identified in 1958 and endemic to parts of Central and West Africa, monkeypox spread rapidly to over 110 countries during its recent outbreak, leading to over 85,860 infections and 93 deaths. Researchers from the State Key Laboratory of Biotherapy at Sichuan University and the School of Pharmacy at Chengdu University in China are spearheading efforts to combat this viral threat. This
Medical News report explores their groundbreaking work, shedding light on the key therapeutic targets and potential drugs to treat monkeypox effectively.
Chinese Scientists Explore New Monkeypox Therapeutic Targets and Drug Repurposing Strategies
Identifying the Challenge
Monkeypox is caused by the Monkeypox Virus (MPV), a double-stranded DNA virus that primarily affects the skin and lymph nodes, manifesting as fever, headache, and characteristic rash. While vaccines have historically offered protection, including smallpox vaccines like ACAM2000, there is a dire need for targeted drugs, especially for severe cases. The lack of standardized treatment options globally poses an urgent threat to public health. Researchers have emphasized that understanding the mechanisms of monkeypox's interaction with human cells is essential to develop effective therapeutic strategies.
A Multifaceted Approach to Drug Discovery
In a bid to address the need for specific treatments, the research team adopted a three-pronged strategy. Their approach involved:
-Updating Monkeypox Data: They comprehensively revised the open reading frame (ORF) database for MPV, detailing the virus's protein-coding genes.
-Constructing Drug Libraries: A robust library of potential inhibitors was compiled, focusing on drugs with previously known antiviral properties.
-Developing a Docking Platform: Using advanced molecular docking techniques, a dedicated Monkeypox Virus Docking Server was launched, allowing researchers to predict interactions between the virus and various drugs.
Key Findings on Viral Targets
The researchers identified 12 critical viral proteins as potential drug targets, each playing a vital role in the virus's replication and survival mechanisms. For instance:
-A49R: A thymidine kinase unique to the virus, making it a promising target for antiviral drugs without affecting human cells.
-C19L: Involved in viral envelope formation, this protein can be effectively inhibited by tecovirimat, an FDA-approved drug.
-I7L: A cysteine protease essential for viral protein maturation, offering another avenue for drug development.
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Through computational techniques like homology modeling and artificial intelligence-based algorithms, the team created 3D structures of these proteins, providing a foundation for designing specific inhibitors.
Drug Repurposing and Screening
To accelerate the discovery process, the team explored repurposing existing drugs. They screened compounds from databases like ChEMBL, DrugBank, and PubChem, identifying 189 candidates with potential activity against MPV. This approach significantly reduces the time and cost associated with developing new drugs from scratch. Some promising candidates included:
-Tecovirimat: Already approved for smallpox, it demonstrated strong inhibitory effects on MPV by blocking viral release from infected cells.
(Thailand
Medical News would however like to add that latest data shows that Tecovirimat might not have efficiency in treating Mpox infections.)
https://www.thailandmedical.news/news/siga-technologies-faces-major-legal-issues-as-its-mpox-drug-tpoxx-tecovirimat-fails-and-its-cmo-is-terminated
https://www.thailandmedical.news/news/u-s-nih-finds-that-tecovirimat-the-mpox-drug-many-countries-were-stockpiling-is-not-effective-against-the-new-clade-1-strain
-Mycophenolate Mofetil (MMF) and Tranilast: Initially used for other conditions, these drugs showed potential against orthopox viruses in early trials.
The Monkeypox Virus Docking Server
The innovative docking server developed by the researchers allows for high-throughput screening of drug-protein interactions. This tool enables scientists to predict the binding affinity of small molecules to viral proteins, facilitating the identification of effective inhibitors. For example, when applied to A49R, the docking tool successfully pinpointed compounds that interacted with its active site, providing a basis for further experimental validation.
Conclusions and Future Directions
The study represents a significant step forward in the fight against monkeypox, combining cutting-edge computational tools with a deep understanding of viral biology. By identifying key viral targets and leveraging existing drug libraries, the researchers have paved the way for rapid therapeutic development.
However, challenges remain. The current drug libraries are limited, and experimental validation of computational predictions is essential. Moving forward, the team aims to expand their database, refine docking methodologies, and collaborate with international laboratories for experimental testing.
The findings underscore the importance of global cooperation in addressing emerging viral threats. As the researchers conclude, the proactive identification of therapeutic targets and the repurposing of drugs can significantly mitigate the impact of outbreaks like monkeypox.
The study findings were published in the preprint journal: PLOS ONE.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0303501
For the latest Mpox News, keep on logging to Thailand
Medical News.
Read Also:
https://www.thailandmedical.news/news/mpox-drug-repurposing-study-yields-promising-insights
https://www.thailandmedical.news/news/plantagoside-and-narcissoside-from-plantago-lanceolata-can-inhibit-monkeypox-mpox-virus-s-profilin-like-protein-a42r
https://www.thailandmedical.news/articles/monkeypox
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