Compound shaped like a tweezer could prove more effective at preventing HIV infection -- and with less side effects -- than other microbicides in development
An unprecedented potential "molecular tweezer" called CLR01, reported in the journal eLife, not only blocks HIV and other sexually transmitted viruses, but also breaks up proteins in semen that boost infection.
Semen is the main vector for sexual HIV transmission. It contains proteins that assemble into very stable polymers called amyloid fibrils, which can enhance HIV infectivity by up to 10,000 times. Scientists led by the University of Pennsylvania (USA) and Ulm (Germany) now show that a molecule with the shape of a tweezer not only destroys HIV particles but also blocks the infection-promoting activity of semen amyloids.
The antiviral activity of CLR01 is based on the way it selectively interacts with and destroys the viral membrane. Remarkably, CLR01 does not affect other cell membranes, which suggests it could be safely incorporated into a vaginal or anal gel to prevent HIV infection - without the risk of side effects.
The way CLR01 operates means that it is also effective against many other sexually transmitted viruses, including Hepatitis C and viruses in the herpes family. It may also be effective against many other "enveloped" viruses including flu and Ebola. The use of other preventive treatments has been undermined in some countries by the stigma associated with HIV. As CLR01 is effective against many viruses besides HIV, it could be more widely acceptable as a general protective agent in communities struggling with HIV stigma.
Moreover, the scientists found that CLR01 also binds to amyloid fibrils and prevents the interaction with viruses that could be exploited by HIV to boost sexual transmission. The tweezer was even found to destroy mature fibrils, which are remarkably stable structures.
"We think that CLR01 could be more effective than other microbicides that are in development because of its dual action, its safety in terms of side effects and its potential broad application," says Professor James Shorter from the University of Pennsylvania School of Medicine.
"The tweezer has been tested and is safe in zebrafish and mice. The next step could be to assess safety and efficacy in non-human primates," says Professor Jan Münch from the University of Ulm.
The scientists anticipate that synthesising CLR01 in large quantities will be straightforward, which will facilitate its development as a microbicide.