syedali73
ELITE MEMBER
- Joined
- Jan 2, 2008
- Messages
- 6,066
- Reaction score
- 60
- Country
- Location
Let me share with you how it works. My team is engineering therapeutic antibodies against certain proteins of HIV. We obtain the sequences of antibody genes and clone them into plasmid vectors. Next we express these vector -borne antibody genes in suitable hosts such as bacteria or mammalian cells and test the ability of expressed and purified recombinant antibodies against viral proteins in in vitro assays. If we find that antibody molecules are working, we try to improve their binding activity through a process called 'direct evolution'. Once we are satisfied with the binding activity (at-least in low nano molar range) of the engineered molecules, we test them in functional assays that involve virulent viruses. Using similar assays, we also study the effect of 'drug pressure' on virus mutation.Amazing Article,
The challenge for researcher is to make an effective research within limited budget.Recently,Pakistan is encountering various challenges which includes viral and bacterial diesease.Since,you are a virologist and very experienced one,therefore I hope that you are aware that how these medicines work.Bacterial receptors for example are targeted.However,those who survived managed to create mutations by changing their receptor sites.
In case of viruses,correct me if I am wrong,viruses mostly survive from drugs by changing their genetic code ie CCG to GCC to prevent molecular drugs from making bonds and destroying it.
Hence,for a reseracher it is greatest challenge to look for suitable compounds which may destroy them.Remember,drugs can be called effective,but they never destory 100% as we let human's immune system to kill the rest.These are the general cases we are discussing.
That is why sometimes,slight change in chemical formula makes drugs very effective as well for specific mutated,survived bacteria.Therefore,we can see in market that some drugs retracted back are again found with ''improved formula'' labelled in them.
----------------------------------------------------------------------------------------------------------------------------------------------------
Coming to the issue,I believe that there is nothing wrong if Indian drugs are paving way in Pakistani market to encounter various dieseases.However,it would be much better if ministry makes investments at Pakistani reserachers and makes sure that they are getting enough funds to built up medicines.
Regards
Like you have correctly pointed out, almost all bacteria and more so viruses mutate to evade drugs. Sometimes it is a silent mutation (mutation in the codon but resulting amino acid remains same) and sometimes not silent i.e. amino acid change. We expose the virus to drugs for several generations and sequence the target DNA (usually that encodes the protein against which drug was tested) obtained from each generation. This gives us an idea of which sequences are highly conserved (mutation in such sequences will prove lethal hence avoided by the virus) and which are not. We try to target highly conserved regions so either the drug itself will take care of the virus or if virus attempts to mutate the specific region, the mutation will result in a defective protein and resulting viruses will be non-infectious.
Even though I have given you example from my work i.e. therapeutic antibodies, but approach is similar for small molecule inhibitors (traditional chemical -based drugs) and peptides.