The scourges of immune-compromised HIV patients have always included opportunistic, chronic infection with other viruses — among them the herpes viruses that cause Kaposi’s sarcoma and chronic cytomegalovirus (CMV) infection.
Before antiretroviral therapy became effective and widely available in the United States, Kaposi’s sarcoma — a form of cancer — was common and sometimes a cause of death among HIV patients. CMV is well known as a cause of pneumonia and diseases of the retina, gastrointestinal tract and neurological system in infants, transplant recipients and in others whose immune systems are weakened.
For HIV patients the threat is greatly reduced when anti-retroviral therapy preserves or restores immune function, but it is not necessarily eliminated.
There’s now hope that clinically useful drugs might emerge from the work of Charles Craik, PhD, a UCSF School of Pharmacy chemist who appears to have found a way to specifically target Achilles’ heels in these herpes viruses.
The importance of CMV infection in particular is being revisited in HIV patients, as CMV now is believed by a growing number of scientists to play a role in the increased susceptibility and earlier onset of diseases associated with aging, even among those in whom the HIV virus is well-controlled. An estimated 95 percent of patients infected with HIV also harbor CMV, as does a large fraction of the broader population. The suspected link between CMV and diseases of aging is thought to be the perpetuation of low-level chronic inflammation by the virus.
It’s still early days for this idea. “It’s controversial whether chronic inflammation – which exists in these patients – is a true independent driver of this process,” meaning accelerated aging, according to UCSF’s Steven Deeks, MD, who studies aging in HIV patients. Deeks is a believer.
Craik has just received a new injection of research funding to pursue his drug strategy. The funds come via a unique competition sponsored by the UCSF Clinical and Translational Science Institute. Finalists for the T1 Translational Catalyst Award, including Craik, received consultation from business leaders with experience evaluating and guiding pharmaceutical ideas toward clinical development.
Down to the lowliest disease-causing virus, every living thing appears to use proteins that chop up other proteins to get anywhere in life. Craik is an internationally recognized expert on these proteins, called proteases. He uses his knowledge of protein structure and molecular interactions to target specific proteases needed by disease pathogens in ways that won’t harm human proteins.
Craik already has decades of experience in identifying protein targets on disease pathogens, including early career work on HIV protease inhibitors. With the new award he plans to further test molecules that might serve as new drugs.