Sea-sponge derivatives able to inhibit HIV
‘The more we know about retroviruses, the better we can find ways to kill them’
Half a dozen novel compounds derived from sea sponges are able to inhibit human immunodeficiency virus (HIV ) in infected cells, according to a newly published study from Simon Fraser University.
These compounds attack HIV’s ability to grow in a way that is different from available drugs, which helps identify weaknesses of the virus that could be exploited by some future therapy, said lead author Ian Tietjen.
“The more we know about retroviruses, the better we can find ways to kill them,” he said.
HIV infection attacks the immune system and, over time, leads to acquired immunodeficiency syndrome, or AIDS.
In particular, bengamide A — derived from a sea sponge native to the waters of Papua New Guinea — was quite potent at concentrations similar to those of many licensed antiretroviral drugs used to treat HIV.
But it inhibits HIV in a way that no licensed drug does, which may also make it useful for treating drug-resistant HIV or as a road map to a therapy that targets replication.
“One of the challenges of HIV is that when it infects a cell, it integrates itself into the host’s DNA, where it stays for the rest of people’s lives, making new virus,” said Tietjen.
The new compound blocks the ability of HIV to create copies of itself from its hiding place.
While this obscure compound may never become a drug, what is potentially more important is the knowledge that HIV can be stopped by attacking the replication process in a particular way, he said.
Natural and synthesized bengamide compounds have shown some promise as cancer drugs and antibiotics.
One version was tested as an anti-cancer agent in a phase one clinical trial, but it was abandoned due to adverse reactions.
“Bengamide A was not toxic to host cells, which is a good sign for being a drug candidate,” said Tietjen. “Of course, that’s completely different from testing bengamide A in an animal or a human, so there’s a long way to go before it becomes a drug.”
The six compounds identified as HIV inhibitors were selected from a field of 252 compounds supplied by chemist Raymond Andersen at the University of British Columbia.
“This was the result of good collaboration with our partners at UBC, who collected sea sponges and other microorganisms from around the world and pulled novel compounds,” said Tietjen.
“They didn’t know what (the compounds) could do and that’s where we came in.”
That the researchers were able to identify so many potentially useful compounds from such a small number of candidates underscores the value of preserving the world’s ecosystems, he said.
“Sometimes we have to test hundreds of thousands of synthetic compounds to get that many hits,” he said.
“The oceans are reservoirs of organisms with all kinds of therapeutic potential.”