The investigational drug lenacapavir is a long-acting antiretroviral drug intended for patients living with HIV whose infections have developed resistance to many different drugs. In contrast to how most antiretroviral drugs work, lenacapavir is a capsid inhibitor, meaning it targets the capsid, or protein shell, that shields HIV’s RNA genome and its associated enzymes. Precisely how lenapapavir interacts with HIV’s capsid has not been clear.

In a study published online on December 8 in iScience, Albert Einstein College of Medicine researchers led by Felipe Diaz-Griffero, Ph.D., show that lenacapavir molecules bind to the capsid protein and stabilize it; this prevents the capsid from opening and releasing the virus’s genetic material, which is a crucial step in HIV-1 infection. According to the researchers, lenacapavir mimics the way the human immune system naturally works to prevent viruses such as HIV from replicating.

Dr. Diaz-Griffero is professor of microbiology & immunology and Elsie Wachtel Faculty Scholar at Einstein.