Monkeypox: Combating a Dangerous Pathogen

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Monkeypox

Monkeypox is a zoonotic pox virus infection that can occur in both humans and some other animals. Monkeypox in humans and animals is caused by infection with the monkeypox virus - a double-stranded DNA virus in the genus Orthopoxvirus, family Poxviridae. Two recognized distinct types are described as the Congo Basin clade and the milder West African clade.

Main Digest

The coronavirus pandemic is far from over. Already another virus is causing a stir: "International outbreak of monkeypox" was the cry in the media a few weeks ago, followed by daily headlines along the lines of "first case of monkeypox in Baden-Württemberg, Bavaria, Berlin and so on". Subsequent reports, like that of Bavaria's public broadcasting service Bayerischer Rundfunk - "Study: monkeypox pathogen mutates faster than expected" - or that of the German weekly news magazine Der Spiegel - "Doctor says of monkeypox: 'We have gone past the point in time where the virus could still have been stopped completely'", did nothing to calm the situation.

And at the latest, since the World Health Organisation (WHO) declared the monkeypox outbreak in more than 50 countries an "emergency of international concern" on 23 July, it should be clear to everyone: Viruses can cross species barriers at any time and cause novel diseases, known as zoonoses, in humans. In extreme cases, they can even trigger another pandemic.

Innovative Approaches to Drug Development

Given this context, it seems more than fitting that the University of Würzburg (JMU) is launching a new research project dealing with this topic. "A structure-based approach to combat zoonotic poxviruses" is its title.

This project, with around EUR 700,000 from the Volkswagen Foundation, is headed by Professor Utz Fischer, Chair of Biochemistry at JMU, and his colleague Dr. Clemens Grimm. Also on board is Intana Bioscience GmbH, a biotech company based near Munich with a special interest in developing new agents. Poxviruses are the focus of this project.

Poxviruses Carry a High Risk Potential

"We know that animals carry many types of viruses in their organism that can pose a threat to humans," says Utz Fischer.

Unfortunately, it is impossible to predict which of them will be the next to make the jump across species barriers. However, it is clear that some viruses have a higher potential than others and are therefore more threatening to humanity, with poxviruses right at the top of this list. Therefore, the project aims to conceive new approaches to developing novel drugs against pox pathogens. To this end, scientists are looking for substances that interfere with the viral transcription process and thus prevent the viruses from multiplying.

Fischer and his team can draw on findings they presented to the public last autumn.

"We succeeded in visualizing the poxviral gene expression machinery at the atomic level," explains the biochemist.

These studies, therefore, allow observing how the molecular machinery acts when the virus multiplies. The images show how the players involved operate during the early phase of transcription.

Approach Can Also be Applied to Swine Fever

With the search for agents that can inhibit these molecular machines, the team can exploit a special circumstance: While many viruses draw extensively on the biochemical resources of the host cell for their multiplication, poxviruses encode their molecular machinery in their genome for this purpose. Important components of this machinery are two enzymes: DNA polymerase, which multiplies the viral genes, and RNA polymerase, which transcribes the viral genes into mRNA.

This unique replication strategy offers the opportunity to search for inhibitors of key viral complexes and enzymes that attack at this exact point and thus spare the host cells, ideally making them free from side effects. Should the team succeed in identifying and designing such molecules, they might even kill two birds with one stone:

"Because the transcription machinery of Poxviridae and Asfarviridae are highly similar, our research is also likely to be of relevance for the economically highly threatening Asfarvirus-linked swine fever disease," says Fischer.

Technical Progress Helps the Research

Technical advances are most helpful to scientists in their work. One of these is a significant increase in the resolution of cryo-electron microscopic images. This technology makes samples "flash-frozen" to temperatures of up to minus 180 degrees Celsius. This makes it possible to examine biological molecules and complexes in solution and reconstruct their three-dimensional structure on the scale of atoms.

The JMU has had a suitable electron microscope for many years.

"Many medically relevant target molecules are becoming the focus of drug design. We will use this technology and established methods to identify molecules that target the special structures of poxviruses and disrupt their multiplication," Clemens Grimm explains.

He carries out structural biology analyses at the department.

Indeed, the scientists involved are optimistic that they will succeed over the coming years in defining several chemical compounds that can serve as a guiding structure for the subsequent development of a pharmaceutical product.

Poxviruses are a Threat for Several Reasons

It is, of course, a coincidence that the research team is starting its work at the same time as this outbreak of monkeypox - the application was written months ago. But what is not a coincidence that scientists focus on poxviruses? After all, these pose a potential threat to humanity for various reasons. For one thing, very few antiviral drugs are currently available, and these often display minimal potency.

In addition, while there is an effective protection against pox infection in the form of vaccination after the World Health Organization (WHO) declared smallpox eradicated in 1980, the corresponding vaccination campaigns were terminated in the ensuing years. Since then, herd immunity to poxviruses has been noticeably dwindling in humans. It is no wonder that a recent study ranks the monkeypox virus as one of the most threatening viruses because of the risk of infecting humans, adapting to its new host through mutations, and then spreading exponentially.

Attribution/Source(s):

This quality-reviewed article relating to our Monkeypox Virus section was selected for publishing by the editors of Disabled World due to its likely interest to our disability community readers. Though the content may have been edited for style, clarity, or length, the article "Monkeypox: Combating a Dangerous Pathogen" was originally written by University of Würzburg, and published by Disabled-World.com on 2022/08/01 (Updated: 2023/10/09). Should you require further information or clarification, University of Würzburg can be contacted at uni-wuerzburg.de/en/home/. Disabled World makes no warranties or representations in connection therewith.

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