- Laboratory studies indicate that a cheap generic drug reduces SARS-CoV-2 infection in human cells by up to 70%.
- The drug, called fenofibrate, regulates cholesterol levels but also destabilizes the spike protein on SARS-CoV-2 and inhibits binding to human cells.
- It was effective against all the SARS-CoV-2 variants that the scientists tested in vitro.
An international effort — involving scientists from Keele University and the University of Birmingham, both in the United Kingdom, and the San Raffaele Scientific Institute in Milan — has found that a drug that people formerly used to control cholesterol levels could be an effective treatment against COVID-19.
The results of the study will appear in the journal Frontiers in Pharmacology.
Researchers first tested several licensed drugs. They were looking for any that disrupted interactions between the viral spike protein — that is, the part of the virus that binds to host cells — and the surface of human cells to see if it would be possible to repurpose the drugs as a COVID-19 treatment.
Co-corresponding study author Dr. Alan Richardson, of Keele University, told Medical News Today: “We tested more than 100 drugs and found that fibric acids had the most potential. Initially, clofibrate looked good, but it has adverse effects, so we then looked at fenofibrate.”
Scientists developed fenofibrate in the 1980s, and doctors used it widely to control people’s cholesterol levels. It was popular until the discovery of statins, which have the added benefit of reducing the risk of heart disease.
Around 30 million people worldwide now take statins. However, some people who cannot tolerate statins still take fenofibrate.
In laboratory experiments, the researchers found that fenofibrate destabilized the spike protein and inhibited binding to the ACE2 membrane protein, through which the virus enters the cells.
Fighting SARS-CoV-2 variants
The drug is effective against the Alpha and Beta variants of SARS-CoV-2, and the team is now investigating its effectiveness against the Delta variant.
“Because the drug affects multiple targets, not just the spike protein, it will be harder for resistance to develop, so new variants should not be able to escape the effect.”
— Dr. Alan Richardson
After experiments with the isolated protein, other researchers in the team repeated the experiments with the live virus and found that fenofibrate was equally effective against the live virus.
Dr. Farhat Khanim, director of research in the School of Biomedical Sciences at the University of Birmingham, tested the drug against the live virus. She was optimistic about its potential.
“We are cautiously very excited. We cannot lose sight of the fact that there are groups of patients at high risk, for whom the vaccine will not work,” she told MNT. “There is still an urgent need to expand our arsenal of drugs to treat SARS-CoV-2 […].”
“The drug seems to work, irrespective of spike mutations,” said Dr. Khanim.
The researchers then looked at how much virus infected cells released after treatment with fenofibrate in vitro. They found that there was a 60% reduction in viral release compared with untreated cells. Other drugs, such as statins, did not have a similar effect.
“Fenofibrate seems to do more than statins.”
— Dr. Farhat Khanim
The viral reproduction and spread among cells are what causes the symptoms as the body tries to control the virus. A drug that reduces that viral release should prevent severe disease and hospitalization and reduce the risk of those with SARS-CoV-2 passing it on to others.
Call for clinical trials
Because people can take the drug by mouth and because the molecule is very cheap, if scientists replicate the recent finding in clinical trials, fenofibrate could prove invaluable for low and middle income countries that have not been able to get ahead with vaccination.
Dr. Richardson added: “Fenofibrate is widely available. We estimate that the cost of a course of treatment would be about £10–20 [$14–28].”
Dr. Peter English, a retired consultant in communicable disease control and immediate past chair of the BMA public health medicine committee, says that “[i]f this in vitro finding translates into a useful clinical effect, it may add another drug to our armory.” Dr. English was not involved with the recent study.
He adds that “[a]t present, however, all of this is fairly speculative because as yet this drug has not yet moved from laboratory-based studies.”
The study authors advise caution around their findings, as all results are from laboratory trials. They are now keen to start clinical trials to assess fenofibrate as a potential therapeutic agent for COVID-19.
“I would like to see clinical trials in high risk populations in the community with symptoms, starting treatment early to see if it prevents hospitalization,” Dr. Khanim told MNT.
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