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New direction for flu drugs
Chemistry World ^ | 21 February 2013 | James Urquhart

Posted on 02/23/2013 11:14:06 PM PST by neverdem

An international team of researchers has developed a new class of anti-flu drug that could prevent new virus strains developing resistance and help control future pandemics while more effective vaccines are prepared. Each year, flu viruses cause up to five million cases of severe illness worldwide, resulting in up to 500 000 deaths.

The preferred drug treatments for flu – neuraminidase inhibitors including Tamiflu (oseltamivir) and Relenza (zanamivir) – treat infection by stopping the viral surface enzyme neuraminidase from interacting with its natural substrate, sialic acid. It is this interaction that releases the virus from an infected cell and allows it to spread to other cells.

The problem, however, is that influenza viruses are constantly evolving and therefore strains have emerged that are resistant to these drugs. There is therefore a pressing need for new drugs that work in different ways.

Now, researchers in Canada, Australia and the UK have developed a new class of mechanism-based covalent compounds that inhibit neuraminidase in such a way that they think it could reduce the chances of flu viruses developing resistance.

'Our plan was to design a molecule that was as close as possible in structure to the natural substrate (sialic acid), because viruses will develop resistance most readily against drugs that radically differ in structure from the natural substrate,' says Stephen Withers, who led the study at the University of British Columbia, Vancouver.

Structure of new flu drug candidates

The drugs mimic the sialic acid target of neuraminidase, then covalently attach to block its activity © AAAS

The team describe the new compounds as ‘Trojan horses’ because they look very much like the natural substrate. But once acted upon by neuraminidase they form a very long-lived covalent intermediate species with the enzyme, thereby blocking the active site from the binding of the natural substrate.

The upshot is the virus cannot mutate its key catalytic residues to stop this covalent attachment. 'If it did so, it would no longer be able to carry out its normal function. Consequently we believe that development of resistance will be much slower, if it occurs at all,' explains Withers.

The compounds have been tested on infected mice, which were completely protected against lethal infection. 'We have already shown that they work well against viral strains that are resistant to Tamiflu or Relenza. We are now embarking on tests to probe whether resistant mutations ever develop against our compounds,' says Withers.

William DeGrado, a pharmaceutical chemist at the University of California, San Francisco, US agrees that this mechanism-based covalent strategy could offer a reduced risk of developing resistance as compared to other existing neuraminidase inhibitors. 'It will be interesting to see whether robust oral bioavailibility can be obtained within this new class of mechanism-based inhibitors,' he comments.

'Oral bioavailability is something we are working on through a pro-drug approach,' says Withers. 'I am very optimistic we can do it.'

References

J-H Kim et al, Science, 2013, DOI: 10.1126/science.1232552




TOPICS: Health/Medicine; Science
KEYWORDS: influenza; microbiology; virology
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1 posted on 02/23/2013 11:14:13 PM PST by neverdem
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To: neverdem

obamacare will not permit this. Too many old people will not die as he is prescibing and this will continue their miserble lives.


2 posted on 02/23/2013 11:22:02 PM PST by DISCO
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To: Mother Abigail; EBH; vetvetdoug; Smokin' Joe; Global2010; Battle Axe; null and void; ...
A Passport to Nanomedicine Success

FReepmail me if you want on or off my combined microbiology/immunology ping list.

3 posted on 02/23/2013 11:25:11 PM PST by neverdem ( Xin loi min oi)
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To: 2ndreconmarine; Fitzcarraldo; Covenantor; Mother Abigail; EBH; Dog Gone; ...

Ping... (Thanks, neverdem)


4 posted on 02/24/2013 1:45:39 AM PST by Smokin' Joe (How often God must weep at humans' folly. Stand fast. God knows what He is doing)
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To: 2ndreconmarine; Fitzcarraldo; Covenantor; Mother Abigail; EBH; Dog Gone; ...

Ping... (Thanks, neverdem)


5 posted on 02/24/2013 1:46:38 AM PST by Smokin' Joe (How often God must weep at humans' folly. Stand fast. God knows what He is doing)
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>> The problem, however, is that influenza viruses are constantly evolving and therefore strains have emerged that are resistant to these drugs.

I’m not contributing to that problem.


6 posted on 02/24/2013 2:19:29 AM PST by Gene Eric (The Palin Doctrine.)
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To: neverdem

Good article.

Never had a flu shot. I must have the immune system of an elephant. Everyone in the house had flu last month but me. Sick all the time as a kid though. Another mystery.


7 posted on 02/24/2013 2:29:28 AM PST by poobear (Socialism in the minds of the elites, is a con-game for the serfs, nothing more.)
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To: neverdem

Iatrogenesis

http://en.wikipedia.org/wiki/Iatrogenesis

Never had a flu shot and most likely never will. I see no compelling reason to screw around with a perfectly working immune system for no reason.


8 posted on 02/24/2013 2:34:51 AM PST by Fzob (In matters of style, swim with the current; in matters of principle, stand like a rock. Jefferson)
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To: Fzob

Plus you never know what new “attributes” they may introduce to your body in the form of a flu shot nowadays. In years past thiswoukd be tin foil hat category but not anymore with the AC sitting on his throne / teeing offa t the nearest golf course. I’d like to see Jeus come back and wrap a 9 iron around his scrawny neck but that wouldn’t be very Christian of me would it? Oh well at least I get some points for honesty...sigh...


9 posted on 02/24/2013 4:34:23 AM PST by jsanders2001
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To: Fzob

Plus you never know what new “attributes” they may introduce to your body in the form of a flu shot nowadays. In years past thiswoukd be tin foil hat category but not anymore with the AC sitting on his throne / teeing off at the nearest golf course. I’d like to see Jeus come back and wrap a 9 iron around his scrawny neck but that wouldn’t be very Christian of me would it? Oh well at least I get some points for honesty...sigh...


10 posted on 02/24/2013 4:34:52 AM PST by jsanders2001
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To: poobear

My one and only flu shot was during the Ford administration. I figured since I commuted by NYC subway and worked as a field tech, in and out of many different offices, it was a good idea. Got deathly ill for a week. Since then I’ve had the flu on occassion, but nothing so bad as when I got that shot. This year, at 68, I had a two day fever, a cough and aches. One more day of weakness and I was back to normal.

Conclusion....NO flu shots for Roccus!


11 posted on 02/24/2013 5:05:58 AM PST by Roccus
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To: Roccus

Good decision. :)


12 posted on 02/24/2013 5:15:20 AM PST by poobear (Socialism in the minds of the elites, is a con-game for the serfs, nothing more.)
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To: Roccus

No flu shots for me either.


13 posted on 02/24/2013 5:19:00 AM PST by bmwcyle (People who do not study history are destine to believe really ignorant statements.)
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To: Fzob
Never had a flu shot and most likely never will. I see no compelling reason to screw around with a perfectly working immune system for no reason.

You gain the most benefit from a flu shot when your immune system is, in fact, working perfectly. A shot "educates" your immune system by "showing" it what the pathogen "looks" like; later, when your immune system encounters that pathogen, it is ready to protect you.

If your immune system does not work perfectly, then a vaccine might not "educate" it very well and the pathogen can still make you sick. Maybe not quite as sick as you would become without the vaccine, but still sick.

14 posted on 02/24/2013 6:16:04 AM PST by exDemMom (Now that I've finally accepted that I'm living a bad hair life, I'm more at peace with the world.)
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To: neverdem; Smokin' Joe

Thanks for posting this and for the ping! I will have to look up the original research report; I find that articles targeted for lay-people leave out crucial details.


15 posted on 02/24/2013 6:19:09 AM PST by exDemMom (Now that I've finally accepted that I'm living a bad hair life, I'm more at peace with the world.)
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To: exDemMom
You gain the most benefit from a flu shot when your immune system is, in fact, working perfectly. A shot "educates" your immune system by "showing" it what the pathogen "looks" like; later, when your immune system encounters that pathogen, it is ready to protect you. If your immune system does not work perfectly, then a vaccine might not "educate" it very well and the pathogen can still make you sick. Maybe not quite as sick as you would become without the vaccine, but still sick.

Don't forget the millions of flu strains out there. If you get vaccinated for the wrong strain you won't necessarily have a strong cross immunity to the unlike strain. You are certainly better off with it(the vaccination) than without it but CDC has guessed wrong in the past.

16 posted on 02/24/2013 6:25:13 AM PST by Cowman (How can the IRS seize property without a warrant if the 4th amendment still stands?)
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To: Roccus
Back in the dark ages (Ford administration) flu shots contained a live virus (it made you sick) that has not been the case for many years.

As we age catching the flu is more dangerous because it can leave you with pneumonia which can easily kill you.

I have not had the flu since I began taking flu shots every year for about 20 years. I don't miss my flu shot and you should reconsider yours.

17 posted on 02/24/2013 6:35:01 AM PST by Ditter
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To: Roccus
My one and only flu shot was during the Ford administration. I figured since I commuted by NYC subway and worked as a field tech, in and out of many different offices, it was a good idea. Got deathly ill for a week. Since then I’ve had the flu on occassion, but nothing so bad as when I got that shot. This year, at 68, I had a two day fever, a cough and aches. One more day of weakness and I was back to normal.

There are a lot of possibilities here.

Did you have an allergic reaction to that shot? Were you exposed to the flu before the shot had time to work (it takes about 2 weeks to develop immunity following a shot)? Did you catch a flu or flu-like illness that was not contained in the shot?

For people who are allergic to the flu shot, there are now flu shots available that are not made in eggs.

The flu vaccine can only protect against 3 (4, in some newer vaccines) kinds of flu. But there are many kinds of flu. Whether or not the shot will protect you depends on how similar the flu you are exposed to is to the (dead) flu contained in the shot.

At your age, the immune system is becoming weak. People over the age of 60 are especially prone to influenza and its complications. One common complication is secondary infections; your body's fight against the influenza virus leaves you susceptible to bacterial infection.

18 posted on 02/24/2013 6:36:12 AM PST by exDemMom (Now that I've finally accepted that I'm living a bad hair life, I'm more at peace with the world.)
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To: Roccus
Back in the dark ages (Ford administration) flu shots contained a live virus (it made you sick) that has not been the case for many years.

As we age catching the flu is more dangerous because it can leave you with pneumonia which can easily kill you.

I have not had the flu since I began taking flu shots every year for about 20 years. I don't miss my flu shot and you should reconsider yours.

19 posted on 02/24/2013 6:39:37 AM PST by Ditter
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To: neverdem

http://www.freerepublic.com/focus/f-chat/1929828/posts


20 posted on 02/24/2013 6:56:08 AM PST by bert ((K.E. N.P. N.C. +12 .....The fairest Deduction to be reduced is the Standard Deduction)
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