Over the past 3 decades of fighting HIV we have become accustomed to using drug cocktails that have been extremely successful at turning HIV into a chronic illness. Despite all the advances in treatment though, the virus still manages to outsmart some of these drugs and resistance to them can build up leading to treatment failure. Also, despite keeping levels of the virus at bay there is still some disease progression. So the search for newer and better treatments continues. Now scientists at Emory University, led by Dr Liotta, have looked at this problem in an entirely new way and might have stumbled onto something exiting.
When HIV infects human cells it integrates into the hosts DNA by interacting with key proteins. It then effectively hijacks the cells machinery and make more copies of itself. There has been some success in developing drugs that block interaction with one of these proteins, CCR5. However HIV also uses another co-receptor CXCR4 to enter cells. So just blocking CCR5 alone won’t do the trick as HIV will just evolve into a more virulent strain that uses CXCR4. You would think the answer is easy, just develop a drug that blocks HIV interaction with CXCR4. However CXCR4 regulates several important inflammatory responses and thus blocking it could lead to severe side effects.
The team of researchers decided to go back to the drawing board and look for compounds that could block both CCR5 and CXCR4 at the same time, whilst avoiding side effects. They designed an inexpensive method to synthesise compounds most likely to work and identified the most effective ones. One of the compounds they found had the added benefit of also blocking HIV reverse transcriptase, an enzyme key in HIV replication. This was an unprecedented finding and one of huge importance as the drug also didn’t affect any of the crucial functions of CXCR4. Furthermore, the compound only targets human proteins and therefore it is unlikely that HIV would develop resistance to it and it was inexpensive to prepare so could be used as a possible affordable alternative to current treatments.
The team are currently working on boosting potency and limiting toxicity and there is still a long way to go but it is very exiting news.