I am studying viruses and I have a question about antiviral drug strategies. Why haven't researchers tried finding small molecule drugs that will bind to receptors on the host cell, thereby preventing viral attachment to the host cell? I feel as though with this strategy, virus resistance and mutation wouldn't be an issue. Thoughts?
According to wikipedia, there have been drugs targeting CCR5 coreceptor approved for treating HIV. These drugs work by binding to CCR5, thereby prevent binding of HIV and CCR5.
However, drug resistance can still develop. Some HIV can bypass it by shifting tropism to CXCR4. While others can increase its affinity to CCR5.
And some receptors are vital for the functions of cells. If we design drugs to these targets, we should make sure that the drugs only prevent binding of viruses specifically without disrupting their normal functions.
Maraviroc was approved for use by the FDA in August 2007.It is the only one thus far approved by the FDA for clinical use, thus becoming the first CCR5 inhibitor. A problem of this approach is that, while CCR5 is the major co-receptor by which HIV infects cells, it is not the only such co-receptor. It is possible that under selective pressure HIV will evolve to use another co-receptor. However, examination of viral resistance to AD101, molecular antagonist of CCR5, indicated that resistant viruses did not switch to another coreceptor (CXCR4) but persisted in using CCR5, either through binding to alternative domains of CCR5, or by binding to the receptor at a higher affinity. https://en.m.wikipedia.org/wiki/CCR5