Nav: Home

A new treatment strategy against MERS

January 29, 2020

Joint press release by Charité and the DZIF

First identified in 2012, the MERS-coronavirus is capable of causing severe and often fatal pneumonia. There are no effective treatments for MERS. Researchers from the German Center for Infection Research (DZIF) at Charité - Universitätsmedizin Berlin recently identified a cellular recycling process known as autophagy as a potential target in the fight against MERS. Autophagy-inducing substances - including certain licensed drugs - were shown to be capable of drastically reducing the rate at which the virus replicates. Results from this research have been published in Nature Communications*.

The MERS pathogen is capable of causing a flu-like illness (Middle East Respiratory Syndrome) which is often associated with pneumonia. Since its appearance in 2012, approximately 2,500 cases have been reported to the WHO across a total of 27 countries. Approximately one third of infections have resulted in death. A team co-led by PD Dr. Marcel Müller of the Institute of Virology on Campus Charité Mitte recently discovered that the MERS virus can only replicate efficiently if it inhibits a cellular process known as autophagy. Based on this initial discovery, the researchers went on to identify substances which are capable of inducing autophagy and can thus be used to limit viral infection.

The term autophagy refers to a type of cellular recycling process which enables cells to dispose of damaged materials and waste products, while retaining intact components for incorporation into new cellular structures. This autophagic degradation, or 'auto-digestion', is also capable of identifying pathogen-derived components, such as the building blocks of viruses, which are treated as waste products and eliminated. A range of viruses are known to have developed strategies to dysregulate or inhibit autophagy. PD Dr. Müller and his colleagues therefore set out to determine whether the MERS virus is capable of modulating autophagic degradation. As a first step, and using stringent biosafety conditions, the researchers infected cells with the MERS virus. Subsequent observations revealed a disruption to the cellular recycling process in cells infected with the virus. "This result clearly indicated that the MERS pathogen benefits from an attenuation of the cellular recycling process," explains PD Dr. Müller.

The researchers also succeeded in identifying a previously unknown molecular switch which regulates the process of autophagic degradation: the SKP2 protein. The researchers discovered that the MERS virus activates this molecular switch in order to slow down the cell's recycling processes and avoid degradation. Using these new insights, the researchers treated MERS-infected cells with various SKP2 inhibitors in order to stimulate the degradation process. This strategy proved successful, the autophagy-inhibiting substances reducing viral replication by a factor of 28,000. Among the substances used to elicit this effect were licensed drugs such as niclosamide, a treatment for tapeworms which had previously been identified as an SKP2 inhibitor. Importantly, niclosamide was shown to be capable of drastically reducing the replication of the MERS virus in cell culture.

"Our results reveal SKP2 to be a promising starting point for the development of new substances capable of fighting the MERS virus, and potentially even other autophagy-dependent viruses," says PD Dr. Müller. SKP2 inhibitors do not target the virus directly. For this reason, the research group leader expects their use to be associated with a reduced risk of resistance. "However, SKP2 inhibitors will need to be tested in vivo before they can be used as drugs. Furthermore, one has to properly evaluate the risks and benefits for their in vivo use, since even drugs that have already been approved can have side effects," says the virologist. The researchers will also test whether SKP2 inhibitors could be effective against other coronaviruses such as SARS or the novel coronavirus (2019-nCoV) which is currently emerging in China.
-end-
*Gassen NC et al. SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection. Nat Commun 10, 5770 (2019).

MERS-coronavirus

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a zoonotic virus (a virus that is transmitted between animals and humans) whose main route of transmission is from dromedary camels to humans. The incidence of MERS infections is highest across the Arabian Peninsula. Human-to-human transmission, while possible, is far less common and usually associated with hospitals. In 2015, this route of transmission was responsible for a larger outbreak in South Korea. Germany has had four documented cases of MERS.

About this study

This study was jointly led by PD Dr. Müller, Dr. Nils Gassen of the University Hospital Bonn (UKB), and Dr. Theo Rein of the Max Planck Institute of Psychiatry.

Charité - Universitätsmedizin Berlin

Related Autophagy Articles:

Lipids, lysosomes, and autophagy: The keys to preventing kidney injury
Lysosomes are cellular waste disposal organelles containing potent enzymes that cause cellular damage if they leak out of ruptured lysosomes.
How zika virus degrades essential protein for neurological development via autophagy
Researchers at the University of Maryland (UMD) shed new light on how Zika virus hijacks our own cellular machinery to break down an essential protein for neurological development, getting it to ''eat itself''.
Autophagy: the beginning of the end
Autophagy, from the Greek for 'self-eating', is an essential process that isolates and recycles cellular components under conditions of stress or when resources are limited.
Cellular cleanup! Atg40 folds the endoplasmic reticulum to facilitate its autophagy
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Institute of Microbial Chemistry investigated 'ER-phagy,' the degradation mechanism of the endoplasmic reticulum (ER), an important organelle with multiple biologically necessary functions like the synthesis of proteins and lipids.
How cells decide the way they want to recycle their content
Researchers from Tokyo Medical and Dental University (TMDU) identified a new phosphorylation site of Ulk1 as a novel regulating mechanism of alternative autophagy.
Autophagy: Scientists discover novel role for self-recycling process in the brain
Proteins classically associated with autophagy regulate the speed of intracellular transport.
Insights into the diagnosis and treatment brain cancer in children
In a recent study published in Autophagy, researchers at Kanazawa University show how abnormalities in a gene called TPR can lead to pediatric brain cancer.
Autophagy degrades liquid droplets, but not aggregates, of proteins
Autophagy is a mechanism through which cellular protein is degraded.
Autophagy genes act as tumor suppressors in ovarian cancer
Researchers at the Medical University of South Carolina and University of California at San Diego report in PLOS Genetics that the loss of BECN1 promoted early ovarian cancer formation and genomic instability.
Mechanism of controlling autophagy by liquid-liquid phase separation revealed
Japanese scientists elucidated characteristics of PAS through observing the Atg protein using a fluorescence microscope and successfully reconstituted PAS in vitro.
More Autophagy News and Autophagy Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.