Question:
Week of April 13, 2002; Vol. 161, No. 15

Vanquishing a Virus: New drugs attack herpes infections
John Travis

Best known for intermittently producing embarrassing sores on the mouth and genitals, herpes simplex virus (HSV) is more dangerous than most people realize. The virus can blind and even kill people with weak immune systems, such as newborns, elderly people, and AIDS patients.

By targeting one of the virus' enzymes, two pharmaceutical companies have now independently identified a new class of drugs that stop HSV from replicating. Scientists rate the compounds as the most promising antiherpes agents developed in 3 decades. Surprisingly, however, there are no current plans to test the experimental drugs in people.

First developed in the 1970s, the compound acyclovir remains the standard drug for treating various forms of HSV. When acyclovir gets into an infected cell, an HSV enzyme activates the drug, leading to the inhibition of a protein the virus uses to copy its own DNA. However, a treated infection may recur, and some strains of the virus are resistant to acyclovir.

Seeking new drug opportunities, researchers have looked at other proteins that the virus relies on to replicate its DNA. More than a decade ago, while at Stanford University, James J. Crute discovered a complex of three HSV proteins that combine into an enzyme called helicase-primase. The virus uses this enzyme to unravel DNA's double helix structure and perform other duties required for replication.

"It was immediately recognized as a really great target for drug discovery," recalls Crute, now at Aurora Biosciences in San Diego.

While working at Boehringer Ingelheim Pharmaceutical in Ridgefield, Conn., Crute and his colleagues developed an assay for screening thousands of compounds for ones that inhibit the helicase activity of the viral enzyme. They identified several compounds that hamper the enzyme's ability to creep along the DNA strand and perform its duties.

Crute's team reports in the April Nature Medicine that these inhibitors block HSV replication in infected cells and also help rodents survive HSV infections. In mice whose genitals had been infected with HSV, one inhibitor slashed the death rate from 60 percent to 10 percent.

Moreover, the new compounds are effective even when given to the mice up to 65 hours after an initial infection. In contrast, for acyclovir to work, it must be taken within hours after the first symptoms appear.

Gerald Kleymann and his colleagues at Bayer AG in Wuppertal, Germany, also have identified inhibitors of HSV replication. After screening more than 400,000 compounds, they realized that the most effective ones were interfering with helicase-primase.

"It appears that we hit the Achilles' heel of the virus," says Kleymann.

Like the Boehringer Ingelheim team, the Bayer group found the compounds to be effective in rodents infected with HSV. In the April Nature Medicine, the Bayer group even reports that its compounds reduce the number of sequelae?the subsequent outbreaks of sores after an initial infection.

"The unsolved problem of herpes infections, namely the sequelae, may become curable," says Kleymann.

Both research groups conclude that helicase-primase inhibitors are more potent than acyclovir and its derivatives.

"People have been looking for years, and nobody had come up with anything that matches acyclovir," notes virologist Priscilla A. Schaffer of Harvard Medical School in Boston. "These compounds are tremendously exciting."

At the moment, though, neither Bayer nor Boehringer Ingelheim plans to launch tests of helicase-primase inhibitors in people. "It's unfortunate because these compounds do look interesting, but companies have to make choices about what they are going to put their money and resources behind," says Paul Anderson, a vice president at Boehringer Ingelheim.

"The fundamental issue is that no pharmaceutical company wants to go head-to-head with acyclovir [and its derivatives]," says virologist Richard Whitley of the University of Alabama at Birmingham. "They do not see it as profitable."

Both pharmaceutical firms say they hope to find other companies willing to finance further testing of their compounds.

"It's kind of depressing," notes Schaffer. "We'd all love to see [a helicase-primase inhibitor] go into the clinic. One of these days, I dare say, it will."

Answer:
Yeah... it's all about money.
Where there are lots of money, things develope.
It's just a result of that people have been taking advantage of democracy. Just a result of that people have been taking advantage of freedom in the name of "their rights".

I think, we HSV patients should find peace in mind no matter what, but on the other hand, we should keep screaming till the money source can't put up with our loud voice and provide enough money for scientists to pursue their job, their passion..

So really.... we don't have time to feel ashamed of having HSV and feel depresssed. :wink:


Faith

Answer:
It's nice that these companies enjoy people having diseases.

It's just a job to them.

Answer:
This is good news...

People decry companies for being interested in money, but it was money and a pursuite of money that built the companies who have the ability to do the research/fund the research in the first place.

If we want companies to throw money considerations out the door for OUR disease, and risk their future to be able to cure us, that's a short term fix which in the long run will not be good for medical research.

We are not victims... We are a potential market...

Obesity is a market

Diabetes is a market

Heart Disease is a market

The common cold is a market

I know it might make us feel better to see companies pissing money into the wind on our behalf, but money flows, as it should, to the biggest market...

Remember, herpes is a VIRUS... the common cold is a VIRUS... HIV is a Virus.... There are billions and billions poured into viral reseach every year.

When there is a promising breakthru, it WILL be profitable for drug companies to pursue it.

Is it all about money.. Hell yes it is... But BELIEVE ME, you WOULD NOT want it any other way.

If it wasn't about money... I assure you, we'd NEVER find cures for diseases...

Answer:
If it wasn't about money... I assure you, we'd NEVER find cures for diseases... <nodding> That's true.
Idealistically, it should be about the mix of money and sense of justice.
But I guess these 2 fight against each other many times.. LOL

Faith

Answer:
Typical... I've come accross so many of these types of articles when I was writing my article... This entire world is driven by money, money and more money... Shit put yourself in their shoes for a second guys... Don't get angry at something like this... Stuff like this should get you excited if anything... If you had the chance to cure something but suffer the loss of millions and millions of dollars, would you do it... Not to mention the jobs and companies that go under if a cure is in fact made for HSV... Pharmaceutical companies would lose too much, thats why you'll never see a cure derived from any of their sources... I wrote this in my article... The cure will come from ppl like us, who invest into private research like this... Heres how I see it straight up... I was thinking of actually doing something like this in some point in my life... I have a private company... Now imagine we collected donations from ppl infected with HSV, even if its like 5 bucks a person, we could collect millions of dollars which would then be transfered into private research like this... Basically the company funds all research without any outside interferance... When a cure is made, that cure belongs to the company, NOT THE pharmaceutical companies who sponser research because it makes them look good... You have to understand that when pharmaceutical companies get close to cures they make millions of dollars on, they usually stop research for reasons such as being too dangerous... My idea is the exact same and comparable to something like sponsering one of these starving kids in Africa or something... If a cure is made, the ppl who donated have their right and access to the cure from the company who they chose to invest in, my company... The ppl own the cure, not the pharmaceutical companies who have nothing to do with it... The cure would be available FREE to doners, while ppl who didn't donate could buy the cure from the comapny for a price... The main thing is donations... Think of the research we could make with a few thousand dollors... This cure your talking about could very well be the answer... It wont go any further however until private research is made... My 2 cents...

Rich