Drug used to lower cholesterol may help treat SARS-CoV-2 variants

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for a pandemic, which has cost over 1.9 million lives worldwide so far. The emergence of new virus variants with higher transmissibility rates is seeing rapid increases in infection rates and deaths across the world. Several vaccines have undergone accelerated approval and are being rolled out worldwide.

While in a few countries vaccination programs are progressing at speed, vaccine uptake rates are variable and for most low middle-income countries, significant proportions of the population are unlikely to be vaccinated until 2022. Furthermore, while vaccination has been shown to reduce infection rates and severity of disease, we are as yet unsure of the strength and duration of the response.

Therapies are still urgently needed to manage COVID-19 patients who develop symptoms and/or require hospitalization. The virus gains entry to human cells by the receptor-binding domain (RBD) of the viral spike protein binding to angiotensin-converting enzyme 2 (ACE2) on human cells. Drugs that block virus binding to ACE2 may substantially reduce virus uptake, thereby reducing/relieving symptoms in patients with an active infection or reduce transmission of the virus to uninfected individuals. 

A study involving scientists from Keele University and the University of Birmingham in the United Kingdom, and the San Raffaele Scientific Institute in Milan, has found that the drug Fenofibrate, formerly used to control cholesterol levels could be an effective treatment against COVID-19. They tested several drugs, 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. They found that fibric acids had the most potential.

Fenofibrate was developed in the 1980s and was used 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.

The researchers found that fenofibrate destabilized the spike protein and inhibited binding to the ACE2 membrane protein, through which the virus enters the cells. The team found that the drug is effective against the Alpha and Beta varians of SARS-CoV-2, and is investigating its effectiveness against the Delta variant. 

After experiments with the isolated protein, another team of researchers repeated the experiments with the live virus and found that it was equally effective against the live virus. Dr. Khanim, co-corresponding author, said that the drug seems to work, irrespective of spike mutations. 

They found that there was a 60% reduction in viral release compared with untreated cells, in vitro. The viral reproduction and spread among cells are what causes 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. 

The authors of the study said that they are keen to start clinical trials to assess fenofibrate as a potential therapeutic agent for COVID-19. Because all the trials had been done in a lab (in vitro), the results are speculative and human clinical trials need to be done in order to recommend it as a treatment. 

Because the drug is cheap and can be taken orally, it could prove invaluable for low and middle income countries that have not been able to get ahead with vaccination.

Source: Scott P. Davies, et al. The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models. Front Pharmacol. 06 August 2021. https://doi.org/10.3389/fphar.2021.660490

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