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Protein Found to Disable RNA Transport in Human Herpes viruses

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Researchers have identified a protein that if inhibited can stops herpes viruses from replicating.  This has implications for various types of herpes viruses.  Researchers eventually would like to turn this into an antiviral drug.  More research needs to be done to confirm its viability. 

Article: http://phys.org/news/2016-11-protein-herpesvirus-rna.html

Paper: http://www.nature.com/articles/nmicrobiol2016201

Quote

A new approach has been developed to combat diseases caused by herpesvirus infections, including everything from cold sores to cancer.

Researchers at the University of Leeds have discovered a way to prevent herpesviruses hijacking important pathways in cells which are required for the virus to replicate and cause disease.

Professor Adrian Whitehouse from the School of Molecular Biology and Astbury Centre for Structural Molecular Biology at the University led the five year study, the results of which are published today in the journal Nature Microbiology.

Professor Whitehouse said: "We've spent several years demonstrating that a protein found in all herpesviruses, recruits a protein complex in the host cell, called human TREX, to help stabilise and transport herpesvirus RNAs out of a cell's nucleus so they are turned into viral proteins.

"Now we have identified a compound which can disrupt this essential virus-host cell interaction which in turn prevents herpesviruses replicating and producing infectious particles."

The approach the researchers used was unique as it targeted the enzyme activity of a key component of the cellular human TREX complex, known as UAP56.  Inhibiting t his activity prevented the remodelling of the human TREX complex which stopped the interaction with the viral protein.

The project is a collaboration between virologists led by Professor Whitehouse and a team of chemists led by Dr Richard Foster also from the University of Leeds. Dr Foster's team performed a virtual screen of thousands of compounds to identify potential inhibitors. These were then tested for their ability to stop herpesvirus replication without damaging the host cell. 

Dr Sophie Schumann, lead author on the Nature Microbiology paper and a member of the research team added: "We initially targeted the human tumour virus known as Kaposi's sarcoma-associated herpesvirus. However, further testing showed that the compound was also effective against a range of other herpesviruses which all use the same mechanism to replicate in their host cell, which is very encouraging."

Examples include Herpes simplex virus which causes cold sores and genital lesions as well as human cytomegalovirus which is associated with glandular fever and a range of conditions in immunocompromised patients and congenitally infected newborns.

Dr Foster said: "We still have a lot of work to do, but bringing together a target point and a compound is a significant finding. Now our job is to improve the quality and potency of the compound before it can operate as a future antiviral drug."

The research so far has been supported in parts by Worldwide Cancer Research, Wellcome Trust, and Biotechnology and Biosciences Research Council.

The next stage of Professor Whitehouse and Dr Foster's work, which is funded by a Cancer Research UK drug discovery award, will work towards improving the effectiveness and safety of the compound.

 

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Second_chance

So as an antiviral will it be like the currents products that are on the shelf, just a little better or will it work to completely stop viral shedding, symptoms, etc? 

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Evaluate

It's too early to say.  They've shown proof of concept and will have to continue researching to figure that out.  Safety and effectiveness will be top of mind and there's no guarantee this research will lead to a marketable antiviral.

That being said, every bit of research is valuable.  While it may or may not lead to an antiviral, it may assist other researchers who are trying to manipulate a herpes virus that leads to a breakthrough.

Edited by Evaluate

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Second_chance

Ugh I just feel like everything is in research and if something does make it to clinical trials...it's not too promising. Everyday I wake up just praying a "breakthrough" occurred, but I just get my hopes up. There's so many of us affected by it but it's like no one seriously cares! Not to single anyone out but there's multiple variations of viagra on the market but we can't find anyone to take HSV serious enough, it's just so frustrating. 

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Evaluate

A cure for herpes is the holy grail of virology, next to HIV.  That is to say it's one of the most difficult nuts to crack in today's line up of viruses.  While I think there are many people who are frustrated, saying that no one is taking it seriously is not accurate.  There are various vaccines, new antivirals and various gene editing techniques that are currently being looked into.  Can more be done?  Absolutely, it would be great to see more government grants given, more sponsorship by pharmacology companies and volunteers jumping in on clinical trials in huge numbers.

It's not a problem that be solved overnight, although all of us would love that.  Hepatitus C did not used to have a cure and now does.  It's a matter of time when the same thing will happen for HSV.

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OFMDH
On 11/13/2016 at 4:30 PM, Evaluate said:

 Safety and effectiveness will be top of mind and there's no guarantee this research will lead to a marketable antiviral.

What they used was a known HSP90 inhibitor (CCT018159) which is already being tried as a cancer treatment. CCT018159 causes diarrhea, fatigue, and the main problem is doubly that its quickly cleared from the body and has very low oral bioavailability. Meaning you'd need to take 40-100 pills of it a day to reach any decent HSV inhibition of replication in humans - such dosing would cause liver damage. I didn't check the analogues tested so unless they find one or I missed something in the research Pritelivir is far superior to this, safer and much closer to market...

 

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