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Scientists search for a cure for HBV
Two grants from the National Institutes of Health will allow Saint Louis University researchers to build on breakthroughs in understanding the hepatitis B virus and begin the search for a drug to cure – not just halt – the illness.
Last year, John Tavis, PhD, professor of molecular microbiology and immunology at SLU published research demonstrating a way to measure and then block a previously unstudied enzyme, RNAseH, to stop the virus from replicating.
Armed with that knowledge, Tavis now has the early data and funding to begin the search for a drug that may help to cure patients with hepatitis B.
Current hepatitis B drugs can treat but not cure the infection for most people. Because the majority of liver cancer cases worldwide are caused by hepatitis B virus, a cure would dramatically cut liver cancer rates.
The assay Tavis found in last year’s research is the measuring tool that allows researchers to gage the RNAseH enzyme’s activity. It is how they will be able to tell if a drug will block the enzyme’s function, and therefore stop the virus. However, until they perfect this measuring tool, they cannot efficiently look for drug candidates to eliminate the hepatitis B virus.
Tavis describes the next stage of the research process as an engineering problem.
“We must re-engineer the assay to be faster and of a better quality,” Tavis says.
There are two problems researchers must resolve in order to move forward.
“First, the current assay is too slow,” Tavis said. “It runs on a gel, which is good for studying how things work, but it isn’t fast enough to look for new drugs. So, we’ll convert it from a gel-based radioactive assay to a faster and easier florescent format. Next, the enzyme is currently at low concentration and not pure enough. So, we’ll make the protein better, in terms of quantity and purity.”
Once researchers have completed meticulous optimizing of both the enzyme and the assay, they will be ready for a small pilot test to screen drug candidates from known drug libraries.
At this point, they will hand the work over to robots, which will screen tens of thousands of potential drug candidates.
“To get the assay ready for the robots, we have to know how we’re going to interpret what we find, to know how to detect what is a hit. That’s what this process is about.”
Additional work funded from a second grant will involve screening for active enzyme from as many hepatitis B virus genotypes as possible. There are eight known genotypes of the hepatitis B virus, each further apart genetically than a person is from a mouse.
Researchers will aim to find drug candidates that work for as many of the virus’s genotypes as possible.
Tavis will partner with Marvin Meyers, PhD, director of medicinal chemistry at SLU’s Center for World Health and Medicine (CWHM) and David Griggs, PhD, director of biology at the CWHM.
The CWHM is dedicated to the development of medicines to treat diseases that affect the world’s poor and underserved populations. The center consists of a multidisciplinary team of former pharmaceutical company scientists with extensive translational research experience. They have the skills to discover and develop small molecule drugs, and they are experienced in advancing such agents into clinical trials.
Initial research funding for Tavis’s work included grants from SLU’s President’s Research Fund, the SLU Cancer Center, and the Friends of the Saint Louis University Liver Center which allowed him to gather enough data to publish initial findings and attract NIH funding.
Source: Saint Louis University Medical Center
Last year, John Tavis, PhD, professor of molecular microbiology and immunology at SLU published research demonstrating a way to measure and then block a previously unstudied enzyme, RNAseH, to stop the virus from replicating.
Armed with that knowledge, Tavis now has the early data and funding to begin the search for a drug that may help to cure patients with hepatitis B.
Current hepatitis B drugs can treat but not cure the infection for most people. Because the majority of liver cancer cases worldwide are caused by hepatitis B virus, a cure would dramatically cut liver cancer rates.
The assay Tavis found in last year’s research is the measuring tool that allows researchers to gage the RNAseH enzyme’s activity. It is how they will be able to tell if a drug will block the enzyme’s function, and therefore stop the virus. However, until they perfect this measuring tool, they cannot efficiently look for drug candidates to eliminate the hepatitis B virus.
Tavis describes the next stage of the research process as an engineering problem.
“We must re-engineer the assay to be faster and of a better quality,” Tavis says.
There are two problems researchers must resolve in order to move forward.
“First, the current assay is too slow,” Tavis said. “It runs on a gel, which is good for studying how things work, but it isn’t fast enough to look for new drugs. So, we’ll convert it from a gel-based radioactive assay to a faster and easier florescent format. Next, the enzyme is currently at low concentration and not pure enough. So, we’ll make the protein better, in terms of quantity and purity.”
Once researchers have completed meticulous optimizing of both the enzyme and the assay, they will be ready for a small pilot test to screen drug candidates from known drug libraries.
At this point, they will hand the work over to robots, which will screen tens of thousands of potential drug candidates.
“To get the assay ready for the robots, we have to know how we’re going to interpret what we find, to know how to detect what is a hit. That’s what this process is about.”
Additional work funded from a second grant will involve screening for active enzyme from as many hepatitis B virus genotypes as possible. There are eight known genotypes of the hepatitis B virus, each further apart genetically than a person is from a mouse.
Researchers will aim to find drug candidates that work for as many of the virus’s genotypes as possible.
Tavis will partner with Marvin Meyers, PhD, director of medicinal chemistry at SLU’s Center for World Health and Medicine (CWHM) and David Griggs, PhD, director of biology at the CWHM.
The CWHM is dedicated to the development of medicines to treat diseases that affect the world’s poor and underserved populations. The center consists of a multidisciplinary team of former pharmaceutical company scientists with extensive translational research experience. They have the skills to discover and develop small molecule drugs, and they are experienced in advancing such agents into clinical trials.
Initial research funding for Tavis’s work included grants from SLU’s President’s Research Fund, the SLU Cancer Center, and the Friends of the Saint Louis University Liver Center which allowed him to gather enough data to publish initial findings and attract NIH funding.
Source: Saint Louis University Medical Center
It's sad to know how they consider HBV as the most virulent diseases yet funding is short. So many people are relying on finding a cure. God help us all to find this soon.
Yes, asian market is very promising. Btw, do asian companies also have to follow fda rules ?
I suppose a cure may also come from other direction, amounts of money pumped into hiv drugs if huge in compare to hbv and probably some of them, which fail for hiv, may work on hbv.
I suppose a cure may also come from other direction, amounts of money pumped into hiv drugs if huge in compare to hbv and probably some of them, which fail for hiv, may work on hbv.
I must agree with your statement. I read about rep9ac as well. I wonder how quick they will have an actual cure for this virus.
i think there are many news from US just because that market is scared of asian/russian market which is coming out with new drugs like mercludex, rep9ac and so on...be sure that they ll move in a bit if an asian drug maker says that got the cure....i think it is just a matter of money and competition...just like any other market
ARC 520 phase II finishes soon, so results probably in a few months
https://clinicaltrials.gov/ct2/show/study/NCT02065336
https://clinicaltrials.gov/ct2/show/study/NCT02065336
I just hope they come out with a cure quick.
I'm 29 with an active hep b which has ruined my life.
The last drug that we had was in 2008 and we are in 2015 judging from this site http://www.hepb.org/professionals/hbf_drug_watch.htm
the next drug which is close to being out are Tenofovir alafenamide and
ABX 203. I'm not sure how effective these drugs are.
I'm 29 with an active hep b which has ruined my life.
The last drug that we had was in 2008 and we are in 2015 judging from this site http://www.hepb.org/professionals/hbf_drug_watch.htm
the next drug which is close to being out are Tenofovir alafenamide and
ABX 203. I'm not sure how effective these drugs are.
Does anyone know about ithe progress of ARC520? How long do u think it'll hit the market for the general public. I hope they find a cure soon.
We may like it or not, but everything is about the money. hcv market in the last year showed that you can earn huge money on the cure so I hope they'll continue with hbv. Drugs are made in accountants offices not in labs ;)
What i can see is lot of news lately on HBV so that is good but wherher i will make it before a cure come out then not sure
this is a very very slow process ...i could have sleep better if i knew something was near ....but we don't have anything but nucs for some years
Each news like this is good :) I hope more funds will be shifted from hcv, which is curable now, to hbv market. There's a huge difference in the money invested at the moment.
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