Could Cat Drugs Treat Humans With Covid-19?

September 22, 2020

Two experimental drugs for cats have the potential to help treat humans infected with COVID-19, according to Science News.

According to the Cornell University College of Veterinary Medicine, a coronavirus that infects only cats causes “feline enteric coronavirus” (FeCV), an infection that affects the gastrointestinal tract and rarely causes any symptoms. However, in about one in ten infected cats, the virus mutates after it infects the animal, allowing it to penetrate specific immune cells, spread throughout the body and cause severe inflammation. At this stage, the infection, known as feline infectious peritonitis virus (FIPV), is often fatal if left untreated.

According to Science News, two experimental drugs have been designed to treat FIPV infections in cats, although neither has been approved by the U.S. Food and Drug Administration (FDA), which reviews animal and human drugs before they hit the market. Nonetheless, preliminary studies suggest that both drugs could be used to knock down human coronaviruses, including SARS-CoV-2, the virus that causes COVID-19.

“The fact that this drug has been developed and has proven successful in treating feline infectious peritonitis is a really good sign,” biochemist Joanne Lemieux told Science News of one of the drugs, called GC376. A second drug, called GS-441524, has also been found to be “very effective in curing feline infectious peritonitis and usually does not require any other form of treatment,” Niels Pedersen, a veterinarian at the University of California, Davis, who studies feline coronaviruses, told Science News.

Both drugs work by preventing feline coronavirus from replicating in cat cells; it may also disrupt the way SARS-CoV-2 replicates in human cells.

GC376, for example, blocks a key enzyme called M protease, which the feline coronavirus relies on to help make copies of its genetic material, called RNA. While replicating, the virus builds long chains of proteins, which the M protease then shreds, separating each individual protein from the next in the chain. The individual proteins then come together to create a new copy of the coronavirus. So if the M protease is destroyed, the feline coronavirus cannot replicate and continues to make cats sick.

Other coronaviruses, including SARS-CoV-2, also use M protease to build copies of the virus, and a 2016 study published in PLOS Pathogens showed that GC376 also prevents M protease from working in SAR-CoV and MERS-CoV, the two coronaviruses that caused respiratory disease in humans in the 2000s The outbreak. This year, a study in the journal Cell Research showed that the drug also prevented SARS-CoV-2 from replicating in test tubes, while another study showed similar results in monkey cells cultured in the lab, according to Science News.

Based on these results, Anivive Lifesciences, the company that manufactures GC376, plans to test the drug in human trials as a treatment for COVID-19.

According to Science News, a second experimental cat drug, GS-441524, has had similar success in animal studies of SARS-CoV-2. The drug works similarly to remdesivir, an antiviral drug that has been shown to shorten the recovery time for hospitalized COVID-19 patients. Susan Amirian, a molecular epidemiologist at Rice University in Houston, told Science News, “Partly because of the research on feline infectious peritonitis, many veterinarians seemed to realize early on in the COVID-19 pandemic that remdesivir could be a promising candidate for COVID-19 treatment in humans.”

Both drugs have a similar chemical structure, resembling a segment of viral RNA – molecules called nucleotides – that link together to form RNA and DNA.When exposed to either drug, the coronavirus enzyme wedges the molecule into the viral RNA, replacing the actual nucleotide, thereby bringing viral replication to a halt. According to the Scope blog published by Stanford Medicine, note that these drugs only work on RNA viral enzymes, not on human enzymes, so they don’t disrupt human DNA replication.

A study published in the journal Cell Reports shows that in addition to blocking the cat coronavirus, GS-441524 also prevents SARS-CoV-2 from replicating in laboratory-cultured monkey and human cells. However, GS-441524 was most effective in monkey cells, while ramivir was more effective than GS-441524 in human lung cells, according to Science News.

Company spokesman Chris Ridley told Science News that biopharmaceutical company Gilead Sciences designed both remdesivir and GS-441524, and has begun early studies comparing the two drugs’ effectiveness against SARS-CoV-2.

Previously, according to Science News, the company said it chose to focus on remdesivir over GS-441524 at the start of the outbreak because remdesivir had already been tested for human safety as an antiviral treatment for Ebola, but the drug was not effective in treating Ebola. While testing remdesivir to treat Ebola, Gilead decided not to seek approval for GS-441524 in animals because the drug is so similar to remdesivir that it may have influenced the FDA approval process in some way, according to The Atlantic. Even now, GS-441524 is not approved for use in cats and is usually purchased as an expensive black market formulation, according to The Atlantic.

Currently, neither GS-441524 nor GC376 has been tested on humans at all.