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| Jarek Duda |
 Posted: Sat Aug 16, 2008 2:10 pm Post subject: Trap for viruses ... |
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Standard approach to fight with viruses is to use antigens which search for some specific place on it's surface, but the problem is that the capsid is varying rapidly.
What usually doesn't change is that the virus still targets to the same molecules on cell's surface - maybe we should try to use it.
For example create empty liposome - water + phospholipid with specific molecules - for example CD4 and some chemokine receptors for HIV.
Now if the virus would catch the bait, it will enter inside and loose its capsid - even if the liposome will be destroyed - it shouldn't longer be a threat or at least much smaller than it would be swimming in capsid.
Eventually we could add inside for example reverse transcriptaze inhibitor or some RNA cutting enzyme.
Imagine such stealth liposom with CD4 - it should swim through veins for a few hours catching viruses, than be consumed with it's content by immune system - perfect scenario.
And remember that every HIV virus has some version of gp120 - should catch the bait... |
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| mike328 |
| Posted: Sun Aug 17, 2008 7:18 pm Post subject: |
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Interesting idea. But you will need much more liposomes than target cells for this to work since this is like a "competitive inhibition" of the virus.
The problem may be how you can get such high amount of liposomes inside the body without causing some type of side effects. Think of it this way, if 9 out of 10 viruses gets trapped in your liposome, but 1 makes it in a cell and multiplies, that single virus will be able to multiply into thousands. Soon, you won't have enough liposomes around. Especially if your immune system attack the virus-containing liposomes.
But I still like your idea. I wonder if there are any virus experts here who can comment on this.
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| Jarek Duda |
| Posted: Sun Aug 17, 2008 10:46 pm Post subject: |
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Modern lyposomes can stays in the veins for a few hours, then are consumed by immune system...
So it would be needed to make regular injections to help cleaning the veins from viruses.
Of course this treatment can/should be connected with treatment targeted to infected cells, but in early stages organism should fight with infected cells itself.
But I agree that the real question is that if required amount is harmless and practical?
Lyposomes should rather be neutral. The problem may be with CD4 - they could (weakly) interact with antigen presenting cells ...
But what quantity is needed to make them competitive with lymphocytes?
They probably could be engineered to be more likely to bind for virus then to lymphocytes...
I couldn't find volume of lymphocytes, but my rough estimation using data from wiki says that it's about a few milliliters...
And I would also preferred that an expert would comment it...  |
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| mike328 |
| Posted: Mon Aug 18, 2008 6:48 am Post subject: |
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| Jarek Duda |
| Posted: Mon Aug 18, 2008 8:39 am Post subject: |
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I didn't thought about it ... yes - erythrocytes it's great idea!
But there is a problem how to create them, I think (?)
I don't think transgenic human would be good option and I would worry that their CD4 would interact with for example pathogen presenting cells, so if used for longer period they could cause problems with the immune system.
We would need to produce large amount of such human compatible erythrocytes to transfuse them ... not using humans ... I believe that it's doable, but it require a lot of work... (?)
Using lyposomes is much simpler - required technology is already known ... and is universal, flows through veins for selected period of time - it's easier to control and should have smaller side effects (?)
A few years ago I also believed that we are living in times that simple good idea should have already been found ...
Then it for example occurred that thought to be closed for a few dozens of years the most fundamental field of data compression - entropy coding, has missed the simplest precise coding technique (ABS/ANS) ...
Believe me - there are still plenty of simple ideas to be found! And searching for them is extremely educating...
About joining a lab - we mathematicians are unpractical in such places |
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| mike328 |
| Posted: Mon Aug 18, 2008 10:54 am Post subject: |
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A mathematician coming up with ideas in biology... thats very cool! I always love to listen in on new ideas, thanks for sharing them!
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| i_feel_tiredsleepy |
| Posted: Mon Aug 18, 2008 12:15 pm Post subject: |
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In a similar strategy, of not attacking the virus, drugs are already in use that target cell receptors to inhibit HIV infection, rather than targetting the virus particles. They have prooved to be quite effective, since humans evolve much slower than HIV.
The concept of using erythrocytes is novel, but I'm not convinced of it's practicallity or cost-efficiency. However, on the subject of foreign erythrocytes, they can be drawn from the patient quite easily, than added back after being manipulated.
Moreover, I don't see any possibility of curing a person with this technique, nor being an effective preventative treatment. |
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| Jarek Duda |
| Posted: Mon Aug 18, 2008 1:19 pm Post subject: |
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Such inhibitor would work great with these traps, which could be constructed to make binding with the virus easier - we should catch most of circulating viruses - greatly reducing infections of new cells!
Final treatment could/should use many parallel attack mechanisms, but ...
production of viruses by infected cell should be very exhausting- they should quickly die or be eaten by immune system (?) - I believe that we could cure illness by 'only' catching viruses from veins...
Everything would be easier to imagine how it really look like, if someone could give some statistics I couldn't find, like:
- what is expected circulating time for a virus?
- how many percents of them infects a cell?
- how long infected cell live and how many viruses is produced in this time?
- do infected cell still catches new viruses with the same probability, or maybe infections protect against this 'waste' of viruses it somehow? If yes, maybe it could be target somehow...? |
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| Jarek Duda |
| Posted: Wed Aug 20, 2008 5:12 am Post subject: |
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I've completely forgotten that capsid proteins stays in the membrane...
This should be the answer to my last question - these proteins can make more difficult entering more viruses to already infected cell (they could infect different cell and it affects very precise infection mechanism so in summarize there should be produced smaller amount of viruses).
That suggest using 'weakened' viruses to inhibit real infections ... but ...
... these proteins should be main target for immune system! Especially that more of them are placed there for creation of new capsids for more viruses ... (this encapsulation should cost a lot of energy, which will be used later to bind to another membrane).
So about using erythrocytes - the more viruses they catch, the less probably they catch more. And after catching a virus - they would be targeted by immune system! We still would have to replace them...
But for using liposoms it's good news - after catching a virus they will present it's capsid proteins, learning immune system - they should have vaccination effect.
We see that they should be made for one virus - very small (remember that they will grow while catching virus).
The problem is that I've heard that most of HIV cell infections happens in lymph? Maybe small liposomes could get to lymph also? (eventually supported by some membrane proteins).
Last edited by Jarek Duda on Wed Aug 20, 2008 6:25 am; edited 1 time in total |
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| TheBiologista |
| Posted: Wed Aug 20, 2008 5:19 am Post subject: |
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| Jarek Duda wrote: |
| I've completely forgotten that capsid proteins stays in the membrane... . |
That really depends on the virus. Usually, capsids are brought into the cytoplasm by one of the endocytosis pathways. They may even translocate to the nucleus before unpackaging. You may be thinking of the viral envelope?
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| Jarek Duda |
| Posted: Wed Aug 20, 2008 7:12 am Post subject: |
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Thanks - I'm sorry - I was thinking about the part that makes fusion with cell's membrane - viral envalope (like for HIV).
I know - the liposomic trap won't work with viruses which enters by endocytosis - it require cell's endocytic mechanisms... |
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| h2so4hurts |
| Posted: Wed Aug 20, 2008 9:53 am Post subject: |
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I've never put much stock into "communicated" articles from PNAS because they aren't peer reviewed (Well, they are, but the authors don't have to make any of the suggested changes).
Interesting idea though, but I think small molecule inhibitors would be much more practical than dialysis with liposome traps.
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| rekorn |
| Posted: Tue Jan 19, 2010 2:16 pm Post subject: |
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| jazzy07 |
| Posted: Tue Feb 02, 2010 7:21 am Post subject: |
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| mike328 wrote: |
| A mathematician coming up with ideas in biology... thats very cool! I always love to listen in on new ideas, thanks for sharing them! |
same here knowledge is infinite, the world has so many things to offer us all we have to do is open our eyes with this resources
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