New York, Aug 7 : A group of medications long prescribed to treat tapeworm has inspired a compound that shows two-pronged effectiveness against Covid-19 in laboratory studies, a new study suggests.
The study, published in the journal ACS Infectious Disease, indicates that the compound, part of a class of molecules called salicylanilides, was designed in the laboratory by a team of researchers, including Kim Janda from Scripps Research.
“It has been known for 10 or 15 years that salicylanilides work against certain viruses. However, they tend to be gut-restricted and can have toxicity issues,” Janda said.
The compound overcomes both issues, in mouse and cell-based tests, acting as both an antiviral and an anti-inflammatory drug-like compound, with properties that auger well for its use in pill form.
The modified salicylanilide compound that Janda created was one of about 60 that he built years ago for another project.
When the SARS-CoV-2 virus became a global pandemic in early 2020, knowing that they may have antiviral properties, he started screening his old collection, first in cells and later in rodent studies.
The study indicated that one compound stood out. Dubbed simply “No 11,” it differs from the commercial tapeworm medicines in key ways, including its ability to pass beyond the gut and be absorbed into the bloodstream — and without the worrisome toxicity.
About 80 per cent of salicylanilide 11 passed into the bloodstream, compared to about 10 per cent of the anti-parasitic drug niclosamide, which has recently entered clinical trials as a Covid-19 treatment, the researcher said.
The experiments showed that of the many modified salicylanilides he had built in his laboratory, No 11 affected pandemic coronavirus infections in two ways.
First, it interfered with how the virus deposited its genetic material into infected cells, a process called endocytosis which requires the virus to form a lipid-based packet around viral genes.
The packet enters the infected cell and dissolves, so the infected cell’s protein-building machinery can read it and churn out new viral copies. No 11 appears to prevent the packet’s dissolution.
“The compound’s antiviral mechanism is the key,” Janda said.
“It blocks the viral material from getting out of the endosome, and it just gets degraded. This process does not allow new viral particles to be made as readily,” the researcher added.
Importantly, because it acts inside cells rather than on viral spikes, questions about whether it would work in new variants like Delta and Lambda aren’t a concern, he adds.
“This mechanism is not dependent on the virus spike protein, so these new variants coming up aren’t going to relegate us to finding new molecules as is the case with vaccines or antibodies,” Janda said.