Artificial Tweezers Block HIV, Herpes And Hepatitis C
August 18, 2015 | by Justine Alford
They're often worn begrudgingly, but let’s face facts: condoms are very good at preventing the spread of STDs, including HIV, for which sex is the most common route of transmission. Of course, they’re not indestructible and thus aren’t 100% effective. Additionally, many people don’t have a choice over whether their partner wears one, like women in resource-poor areas.
It’s for these reasons that scientists are keen to develop topical microbicides, like gels or creams, as an effective yet discreet intervention strategy to prevent new HIV infections. Unfortunately, despite promising early results from numerous studies, all have so far proved a flop in clinical trials. But if at first you don’t succeed, try, try, try again: there’s now a new candidate on the block, and it actually seems to be a bit of a jack of all trades.
Described as a “molecular tweezer,” this compound not only destroys HIV but also a range of other viruses, including herpes and hepatitis C. On top of all that, it even eliminates protein bundles in semen that enhance the transmission of HIV, thus representing a two-pronged attack whereby both host and viral factors are targeted.
The artificial tweezer, called CLR01, was actually developed more than a decade ago as a way to specifically engage certain building blocks, or amino acids, of proteins. Realizing that one of the amino acid targets – lysine – is found in abundance in tangles of proteins in semen that are known to dramatically boost HIV infectivity, scientists from the University of Pennsylvania wondered whether CLR01 might be able to inhibit their assembly.
As predicted, the scientists found that the tweezers successfully targeted these HIV-promoting protein bundles, called amyloid fibrils. By engaging with lysine residues, CLR01 both inhibits the formation of these fibrils and prevents their formation, the researchers describe in eLife. But their observations demonstrated that it has another, unanticipated trick up its sleeve: it also seems to be able to interfere with protein structures found on the surface of HIV, collectively called the viral envelope.
“The surprise for us came when we discovered it had an unexpected activity against HIV itself and directly disrupts the viral envelope,” study author James Shorter told IFLScience. “It also appears to disrupt the envelope of human cytomegalovirus, herpes simplex virus, and hepatitis C virus, and so we wonder whether it may also have activity against enveloped viruses.” Interestingly, he adds, it has so far proved ineffective against viruses without these structures, or non-enveloped viruses.
Because CLR01 seems to exert a broad spectrum of activity, Shorter thinks that the viral target is probably not a protein, but rather some feature of its membrane that could be common to multiple viruses. For example, viral envelopes have a distinctive composition of fats that can bunch together in discrete areas, so the tweezers may be engaging with these.
While they don’t know the precise target yet, the team did find that CLR01 left cell membranes alone when tested out on tissue culture in the lab. This specificity meant that it exhibited minimal toxicity, which is encouraging. And in combination with the dual mode of action, which differentiates it from others previously developed, CLR01 could be particularly effective.
Of course the proof will be in the pudding, but University of Warwick HIV researcher Emma Anderson, who was not involved in the research, thinks the findings are promising: "The paper uses a nice range of techniques – biophysical, biochemical, modeling, virological – and the results make a very nice story," she told IFLScience. "The next step will be to test it in vivo, and of course many potential drugs fall down at this stage."
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