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Author Topic: Puzzle about integrase found  (Read 3209 times)

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Offline veritas

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Offline Rev. Moon

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Re: Puzzle about integrase found
« Reply #1 on: January 31, 2010, 05:02:21 PM »
No intro, just link and run?  Unacceptable, veritas :)

Actually that is quite the fascinating find.  This will hopefully be good to address potential resistance issues.
"I have tried hard--but life is difficult, and I am a very useless person. I can hardly be said to have an independent existence. I was just a screw or a cog in the great machine I called life, and when I dropped out of it I found I was of no use anywhere else."

Offline veritas

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Re: Puzzle about integrase found
« Reply #2 on: January 31, 2010, 05:07:56 PM »

I thought the article would say it all.

Possibilities  could  be mindboggling.

Cheers,


v

Offline Inchlingblue

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Re: Puzzle about integrase found
« Reply #3 on: January 31, 2010, 06:32:44 PM »
It's good to see the doggedness of these scientists — 40,000 trials in 4 years in order to learn the three-dimensional structure of integrase!

If this discovery leads to a way to develop integrase inhibitors that HIV is not able to become resistant to, that would be remarkable.  

This discovery is closely related to this other recent one, in which it was found that HIV evades certain sites in the human genetic material when it integrates:

http://www.sciencedaily.com/releases/2009/11/091112103413.htm
« Last Edit: January 31, 2010, 06:38:07 PM by Inchlingblue »

Offline John2038

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Re: Puzzle about integrase found
« Reply #4 on: January 31, 2010, 06:54:15 PM »
wowwow

Thank's V !

Video http://www.physorg.com/news184141480.html

Can't wait to celebrate the death of HIV !
One step closer

Offline xman

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Re: Puzzle about integrase found
« Reply #5 on: January 31, 2010, 06:58:57 PM »
Well it wouldn't be the death for HIV but a new temporary bandaid for stopping the virus replication. No cure. No eradication. Obviously a remarkable step foward but we are still condemned for lifelong treatment.
sign the petition launched by the aids policy project addressed to the nih aimed to increase the money needed to find the cure:

http://www.aidspolicyproject.org/petition_for_the_nih

we can make a difference and we need to fight. please support them! it doesn't cost you anything. they need it now more than ever!

Offline veritas

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Re: Puzzle about integrase found
« Reply #6 on: January 31, 2010, 07:13:47 PM »
John,


The sentence that caught my eye in your link:

"Availability of the integrase structure means that researchers can begin to fully understand how existing drugs that inhibit integrase are working, how they might be improved, and how to stop HIV developing resistance to them".

This means, possibly, one drug, relatively AE free.

I can live with that!

v

Offline J220

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Re: Puzzle about integrase found
« Reply #7 on: February 01, 2010, 01:53:01 AM »
Just read this too, very encouraging! Many possiblities could derive from this, I think. Excellent!
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline Inchlingblue

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Re: Puzzle about integrase found
« Reply #8 on: February 01, 2010, 10:04:56 AM »
Just read this too, very encouraging! Many possiblities could derive from this, I think. Excellent!

Did you mean to add a link? Not sure what you mean by "Just read this too"

For a lightly more technical, but still accessible version of the story of this discovery,

Scientists Solve 3-D Crystal Structure of Retroviral Integrase Bound to Viral DNA

One of the things they say is, “Our findings will allow the generation of reliable HIV-1 integrase and integrase strand inhibitor pharmacophore models, which will be invaluable for the development of next-generation strand-transfer inhibitors.”

LINK:

http://www.genengnews.com/news/bnitem.aspx?name=74423430
« Last Edit: February 01, 2010, 10:40:14 AM by Inchlingblue »

Offline J220

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Re: Puzzle about integrase found
« Reply #9 on: February 01, 2010, 12:02:52 PM »
Did you mean to add a link? Not sure what you mean by "Just read this too"

Oh sorry about that, I meant that I had read about the news, in general. I usually pick up the releases at sciencedaily.com:

http://www.sciencedaily.com/releases/2010/01/100131142438.htm

ScienceDaily (Jan. 31, 2010) — Researchers have made a breakthrough in HIV research that had eluded scientists for over 20 years, potentially leading to better treatments for HIV, in a study published The researchers, from Imperial College London and Harvard University, have grown a crystal that reveals the structure of an enzyme called integrase, which is found in retroviruses like HIV. When HIV infects someone, it uses integrase to paste a copy of its genetic information into their DNA.

Prior to the new study, which was funded by the Medical Research Council and the US National Institutes of Health, many researchers had tried and failed to work out the three-dimensional structure of integrase bound to viral DNA. New antiretroviral drugs for HIV work by blocking integrase, but scientists did not understand exactly how these drugs were working or how to improve them.

Researchers can only determine the structure of this kind of molecular machinery by obtaining high quality crystals. For the new study, researchers grew a crystal using a version of integrase borrowed from a little-known retrovirus called Prototype Foamy Virus (PFV). Based on their knowledge of PFV integrase and its function, they were confident that it was very similar to its HIV counterpart.

Over the course of four years, the researchers carried out over 40,000 trials, out of which they were able to grow just seven kinds of crystals. Only one of these was of sufficient quality to allow determination of the three-dimensional structure.

Dr Peter Cherepanov, the lead author of the study from the Department of Medicine at Imperial College London, said: "It is a truly amazing story. When we started out, we knew that the project was very difficult, and that many tricks had already been tried and given up by others long ago. Therefore, we went back to square one and started by looking for a better model of HIV integrase, which could be more amenable for crystallization. Despite initially painstakingly slow progress and very many failed attempts, we did not give up and our effort was finally rewarded."

After growing the crystals in the lab, the researchers used the giant synchrotron machine at the Diamond Light Source in South Oxfordshire to collect X-ray diffraction data from these crystals, which enabled them to determine the long-sought structure. The researchers then soaked the crystals in solutions of the integrase inhibiting drugs Raltegravir (also known as Isentress) and Elvitegravir and observed for the first time how these antiretroviral drugs bind to and inactivate integrase.

The new study shows that retroviral integrase has quite a different structure to that which had been predicted based on earlier research. Availability of the integrase structure means that researchers can begin to fully understand how existing drugs that inhibit integrase are working, how they might be improved, and how to stop HIV developing resistance to them.
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline sensual1973

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Re: Puzzle about integrase found
« Reply #10 on: February 02, 2010, 02:15:02 PM »
am sick and tired of reading about a discovery after discovery and how it is hailed as a breakthrough.how many discoveries since HAART ? where are they ? and did anything good came out of them ? .....nope.
God grant me the serenity to accept the things i can not change.

Offline xman

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Re: Puzzle about integrase found
« Reply #11 on: February 02, 2010, 02:58:12 PM »
am sick and tired of reading about a discovery after discovery and how it is hailed as a breakthrough.how many discoveries since HAART ? where are they ? and did anything good came out of them ? .....nope.

The problem is that the timeline for those discoveries evolving in practical applications is too long. A discovery is everytime a step foward but it is useless until you have something concrete to give patients.
sign the petition launched by the aids policy project addressed to the nih aimed to increase the money needed to find the cure:

http://www.aidspolicyproject.org/petition_for_the_nih

we can make a difference and we need to fight. please support them! it doesn't cost you anything. they need it now more than ever!

Offline Hellraiser

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Re: Puzzle about integrase found
« Reply #12 on: February 02, 2010, 03:07:12 PM »
Yeah.  If something big happens I promise these boards most likely won't be the first place you'll hear about it.  We have our ear to the ground, but what you're waiting for is an earthquake.

Offline John2038

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Re: Puzzle about integrase found
« Reply #13 on: February 02, 2010, 04:04:57 PM »
Even for a marathon, the first step have to be made. One day it may happen that the study we are reading will be lead to the cure tomorrow. I also prefer little steps than no step at all. Finally, I can't understand the needs to complain when we have the freedom to read what ever we want to read.

Offline MYSTERY

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Re: Puzzle about integrase found
« Reply #14 on: February 02, 2010, 06:20:10 PM »
I guess I can understand the frustration that we all face in hopes of a quick fix to our problems, but that isn't going to happen. We all must keep in mind that those little steps we have made throughout the years have enabled many of us to still be around to enjoy life today.

Atheist don't believe in GOD, but GOD believes in them and loves them. Never let the failure of man conflict with your love of GOD.

Offline J220

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Re: Puzzle about integrase found
« Reply #15 on: February 03, 2010, 12:18:59 AM »
We wouldn't have HAART today if it were not for small steps over a long period of time....so while most of these "small" discoveries may not seem like much, they are all steps in the right direction. They will eventually add up to something, the same way that previous discoveries led to HAART.
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline leatherman

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Re: Puzzle about integrase found
« Reply #16 on: February 04, 2010, 05:59:09 PM »
I was just talking to someone that is changing meds, and was glad to hear that he had stuck with the old meds until his doctor could make a switch. That situation made me think about some of the issues I had in the past. Because of some resistance issues that I faced, three times since 1992, I have literally had NO med that I could take that would affect my HIV virus. That's pretty f-ing scary to know while everyone else has meds keeping them alive, my virus was rampaging unchecked because of it's mutations. Thankfully over the last decade several over meds have come to the market and I'm on a regimen that got me to undetectable - for the first time after I was diagnosed with AIDS over 18 years ago.

So while YOU may see no advances of any worth to you, sensual, some of those recent advances are still giving some of us the gift of life. ;)

Until a cure is found (which I, IMHO, doubt ever happens, quite frankly, as there are many illnesses out there that haven't been cured for a much longer time), I'm pretty happy with these smaller discoveries. You see, if that cure isn't found, resistance may be something we will all succumb to. In that scenario, we'll all be thankful for each for these smaller discoveries and the meds developed to take advantage of that new-found knowledge.

Though you might long for a cure to be here today (and who among us doesn't want that?), don't diss the very discoveries that might be the reason you are able to cling to life long enough to get to that cure. Though AZT-monotherapy was horrendous and nearly killed me, I also believe that it gave me the extra time until other meds came to market, unlike my partner who died in 94 because there wasn't anything else to take.
leatherman (aka mIkIE)


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