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Samuels Professor and chair of biochemistry at the University of Utah, laid the foundation for the development of a highly effective, long-lasting prophylactic against HIV, a top scientific journal. The drug lenacapavir, developed by Gilead Sciences, provides protection for half a year instead of one day and has performed extremely well in clinical trials.
Sundquist鈥檚 research focuses on understanding how the HIV virus is built on a molecular level and how it interacts with the body to infect and spread through cells.
By purifying and analyzing the protein shell that surrounds the virus鈥檚 genetic material, Sundquist鈥檚 team discovered what the shell looks like and how it鈥檚 put together. Importantly, the research team found that the virus鈥檚 shell is highly sensitive to changes. Making even small tweaks to the proteins that make up the shell stopped the virus from replicating as quickly, which suggested that drugs that affect the protein shell could prove to be effective.
These insights prompted pharmaceutical company Gilead Sciences to search for drugs that target HIV鈥檚 protein shell, with Sundquist as a consultant. They ultimately developed lenacapavir, which binds the viral protein shell, preventing it from assembling properly and productively entering the nucleus of host cells. The drug is now used as a second-line treatment for HIV when the virus is already resistant to multiple other drugs.
But lenacapavir鈥檚 standout potential is for preventing HIV entirely. 鈥淟enacapavir phase three clinical trials for the prevention of HIV transmission have been spectacularly successful,鈥 Sundquist says. 鈥淚t鈥檚 more potent than any drug available, but more importantly, it鈥檚 very long-lasting and effective.鈥
While other pre-exposure prophylactics (PrEP) against HIV have to be taken every day, a dose of lenacapavir provides protection for six months. Especially in contexts where people have limited access to medical care, the longer duration of lenacapavir leads to a marked difference in outcomes.
In large clinical trials in South Africa and Uganda, over the course of the study. Follow-up trials in other populations, including men and nonbinary people, have confirmed the drug鈥檚 efficacy. 鈥淟enacapavir almost completely prevents the transmission of HIV into at-risk populations,鈥 Sundquist sums up. 鈥淭his is just an amazing result.鈥
Despite its impacts on human health, Sundquist sees his lab鈥檚 work as motivated primarily by discovery. 鈥淲e鈥檙e driven by curiosity to discover things that we don't understand,鈥 he says. 鈥淚t鈥檚 not so different from other kinds of adventures. The same thing that drives people to climb mountains drives us to discover how molecular machines work.鈥
