The drugs mimic the sialic acid target of neuraminidase, then covalently attach to block its activity © AAAS
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.
The drugs mimic the sialic acid target of neuraminidase, then covalently attach to block its activity © AAAS
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.'
J-H Kim et al, Science, 2013, DOI: 10.1126/science.1232552
obamacare will not permit this. Too many old people will not die as he is prescibing and this will continue their miserble lives.
FReepmail me if you want on or off my combined microbiology/immunology ping list.
Ping... (Thanks, neverdem)
Ping... (Thanks, neverdem)
>> 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.
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.
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.
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...
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...
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!
Good decision. :)
No flu shots for me either.
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.
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.
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.
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.
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.
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.
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