German study in 2022 found that Nitroxoline could be repurposed to treat Monkeypox (Mpox)

Medical News: In 2022, a team of German researchers embarked on a groundbreaking study exploring potential treatments for Monkeypox (Mpox), a viral infection causing global concern due to its resurgence and spread. The researchers, from institutions including Goethe University, Frankfurt am Main, and Charité-Universitätsmedizin, Berlin, focused their attention on nitroxoline, an antibiotic commonly used to treat urinary tract infections. This Medical News report will explore the study's findings, the mechanism behind nitroxoline’s antiviral properties, and its potential impact on the treatment of Mpox.


German study in 2022 found that Nitroxoline could be repurposed to treat Monkeypox (Mpox)

The Need for New Treatment Options
Mpox is a zoonotic virus, primarily transmitted through contact with infected animals, but in recent years, human-to-human transmission has increased, leading to widespread outbreaks. Current treatment options for Mpox include tecovirimat, brincidofovir, and cidofovir, three antiviral drugs that are considered effective. However, these treatments come with limitations. Brincidofovir and cidofovir have been associated with severe side effects, and tecovirimat, while effective, faces challenges such as limited availability and the risk of resistance development. As a result, researchers have been exploring other readily available drugs that could offer a safer and more effective solution for treating Mpox.
 
Why Nitroxoline?
Nitroxoline is an antibiotic used for over 50 years to treat uncomplicated urinary tract infections. It works by inhibiting bacterial enzymes required for their growth and replication. What intrigued the researchers about nitroxoline was its unique ability to inhibit specific signaling pathways that Mpox uses to replicate within human cells. This antibiotic inhibits the Phosphoinositide 3-kinase (PI3K) and RAF/MEK/ERK pathways, which are crucial for the replication of orthopoxviruses, including Mpox.
 
The German team hypothesized that nitroxoline, with its dual antiviral and antimicrobial properties, could serve as a repurposing candidate for Mpox treatment. Their study, which tested the drug against 12 Mpox virus isolates from the ongoing outbreak, provided compelling results.
 
Key Findings from the Study
The researchers observed that therapeutic concentrations of nitroxoline effectively inhibited Mpox replication in both human keratinocytes and fibroblasts. In particular, the drug prevented the virus from completing its replication cycle, which significantly reduced the viral load in the infected cells. This discovery is crucial because it shows that nitroxoline has the potential to act not only as an antibiotic but also as an antiviral agent that disrupts Mpox virus replication.
 
The team tested nitroxoline on a skin explant model, a technique that allows researchers to study the effects of the drug on human skin tissue. The results demonstrated that nitroxoline could reduce Mpox infection in skin tissue, providing further evidence of its potential efficacy in treating patients.

Interestingly, while tecovirimat, one of the existing treatments for Mpox, often led to the development of resistance in the virus, nitroxoline showed no signs of inducing resistance. Moreover, nitroxoline r emained effective against tecovirimat-resistant strains of the virus, suggesting it could be an essential tool in the fight against Mpox, particularly when used in combination with other antiviral drugs.
 
Dual Action: Antiviral and Antimicrobial Properties
Another critical finding of the study is nitroxoline's ability to target not only the Mpox virus but also bacterial pathogens often co-transmitted with the virus. Mpox infections are sometimes complicated by secondary bacterial infections, which can exacerbate the condition and lead to more severe outcomes. Nitroxoline's antibacterial properties offer a dual benefit, making it an even more attractive candidate for repurposing.
 
Researchers found that nitroxoline inhibited the growth of Escherichia coli (E. coli) and Neisseria gonorrhoeae, two bacterial pathogens that are commonly found in patients with Mpox. This dual-action property makes nitroxoline a unique and promising option for patients suffering from both viral and bacterial infections, potentially reducing the need for multiple drugs during treatment.
 
Synergistic Effects with Other Antivirals
One of the most promising aspects of nitroxoline is its ability to enhance the antiviral effects of existing Mpox treatments. The study showed that when nitroxoline was used in combination with tecovirimat and brincidofovir, the antiviral activity of these drugs increased. This finding suggests that nitroxoline could be used in combination therapies to improve treatment outcomes and potentially reduce the chances of resistance development.
 
In particular, the study found that nitroxoline and brincidofovir worked synergistically, meaning that their combined effects were greater than the sum of their individual actions. This discovery paves the way for further research into combination therapies that could be more effective than single-drug treatments.
 
What This Means for the Future of Mpox Treatment
The discovery that nitroxoline can inhibit Mpox replication and prevent resistance development is a significant step forward in the search for effective Mpox treatments. Its ability to act as both an antiviral and an antimicrobial agent makes it a versatile tool that could simplify treatment regimens for patients with Mpox.

Furthermore, the fact that nitroxoline is already an approved drug with a well-known safety profile means that it could be repurposed quickly for Mpox treatment, avoiding the lengthy process of developing and approving new antiviral drugs. This is particularly important given the current global Mpox outbreaks and the need for immediate, effective treatment options.

The findings of this study highlight the potential of drug repurposing as a strategy for addressing emerging viral threats. By identifying existing drugs that can be repurposed for new uses, researchers can expedite the development of treatments for diseases like Mpox, where time is of the essence.

Conclusions
The German study in 2022 demonstrated that nitroxoline is a promising candidate for the treatment of Mpox, with its ability to inhibit viral replication, prevent resistance, and target co-transmitted bacterial pathogens. Its synergy with existing antiviral drugs further enhances its potential as part of a combination therapy for Mpox patients.
 
In conclusion, nitroxoline's dual action as an antiviral and antimicrobial agent makes it a strong candidate for repurposing. With further clinical trials and research, this drug could become a critical component in the fight against Mpox, offering a safe, effective, and readily available treatment option.
 
The study findings were published in the peer-reviewed Journal of Medical Virology.
https://onlinelibrary.wiley.com/doi/10.1002/jmv.28652
 
The preprint version was published in December 2022.
https://www.biorxiv.org/content/10.1101/2022.12.29.522228v1.article-metrics
 
Thailand Medical news would like to add that while this study was done in 2022 and the peer reviewed version was published in January 2023, despite certain successful observational and small randomized clinical trials conducted in Germany, Spain and Brazil, the results of these clinical trials were never published and no major health agency bothered to incorporate nitroxoline into treatment protocols for Mpox despite it being a cheap and generic drug. We strongly feel that more studies should be conducted to utilize it as an adjuvant with existing treatment protocols.

For the latest Mpox News, keep on logging to Thailand Medical News.
 
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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
 
https://www.thailandmedical.news/news/chinese-researchers-warn-that-current-vaccines-are-inefficient-in-protecting-against-emerging-mpox-virus