Inhibition of reverse transcriptase

[Andrew, Tel. +396-91093434]

In reply to the message:

[snip]
>I have just finished an AP highschool level Biology course, and one question
>st
>ill erks me: if enzymes
>are so specific and many have alosteric inhibitory binding sites, is it
>possibl
>e to find a substrate that
>could inhibit the function of reversetranscriptace in retroviruses either
>throu
>gh competitive or allosteric
>inhabition?  I hope I have not violated any rules of this group by posting
[snip]

Dear Jason,

   Yes indeed, it is possible to find compounds which inhibit reverse
transcriptase and in particular much effort (and money) has been expended over
the last several years by various organizations and individuals to find
inhibitors of the reverse transcriptase of HIV. (I presume you were thinking
along these lines?) Many of these compounds function very well in the test
tube but beyond that there are many difficulties in using these on people,
usually because of one or more of the following problems:

1) The compound is too toxic to be used safely in treating people with HIV.

2) Treatment with even safe and "test tube effective" compounds results in the
rapid appearance of mutant HIV strains which are resistant to the drug.

   This appears to apply also to compounds which are active against other
viral enzymes, such as the HIV protease. For an example of this phenomenon
there was a recent article in Nature where HIV-infected patients were treated
with a variety of different protease inhibitors. In all cases drug-resistant
strains of the virus eventually emerged which were not only resistant to the
original drug used on the patient but were also cross-resistant to the other
anti-protease drugs tested.

   They are now hoping that treatment with combinations of drugs having
different activities will be effective. I hope so.


   Andrew

   P.S. Polite and intelligent questions like yours are always welcome on
Bionet, so, Jason, don't be put off. Responses to the above posting are also
welcome, despite the heat created by the Ebola uproar. Sheesh.

===============================================================================
        Andrew Wallace, IRBM P. Angeletti, Pomezia, Italy.

               	Voice: +39-6-91093434
               	Fax:   +39-6-91093225
               	Email: wallace at irbm.it

 Discussion on phage display, combinatorial libraries, etc. - molreps at irbm.it
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DISCLAIMER: I speak only for myself.