Could cat drugs treat humans with COVID-19?

 Stolen from Livescience.com by Best in Moderation

https://www.livescience.com/cat-coronavirus-drugs-treat-human-COVID-19.html

Two experimental drugs for cats could potentially help treat humans infected with COVID-19, Science News reported.

A type of coronavirus that only infects cats can cause "feline enteric coronavirus" (FeCV), an infection that affects the gastrointestinal tract and seldom causes any symptoms, according to the Cornell University College of Veterinary Medicine. However, in about one in 10 infected cats, the virus mutates after infecting the animal in a way that lets it infiltrate specific immune cells, spread throughout the body and set off severe inflammation. At this stage, the infection is called "feline infectious peritonitis virus" (FIPV) and is usually fatal if left untreated.

Two experimental drugs have been designed to treat cats with FIPV, although neither has been approved by the U.S. Food and Drug Administration (FDA), which vets both animal and human drugs before they enter the market, according to Science News. That said, preliminary research hints that both drugs could be used to take down human coronaviruses, including SARS-CoV-2, the virus that causes COVID-19.

"The fact that this drug has already been developed and shown to be successful in treating feline infectious peritonitis, it really bodes well," biochemist Joanne Lemieux told Science News about one of the drugs, called GC376. The second drug, called GS-441524, has also been found to be "highly effective in curing cats with feline infectious peritonitis, and usually without any other form of treatment,” Niels Pedersen, a veterinarian who studies the feline coronavirus at the University of California, Davis, told Science News.

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

GC376, for example, hobbles a key enzyme called M protease that the feline coronavirus relies on to help make copies of its genetic material, known as RNA. While replicating, the virus builds long strands of proteins that M protease then chops up, to separate each individual protein from the next in the chain. The individual proteins then come together to build a new copy of the coronavirus. And so if  M protease is damaged, the feline coronavirus cannot replicate and continue to make cats sick.

Other coronaviruses, including SARS-CoV-2, also use M protease to build copies of the virus. A 2016 study, published in the journal PLOS Pathogens, revealed that GC376 also stops M protease from working in SAR-CoV and MERS-CoV, two coronaviruses that caused outbreaks of respiratory disease in humans in the 2000s. This year, a study in the journal Cell Research suggested that the drug can also stop SARS-CoV-2 from replicating in a test tube, while another study showed similar results in lab-grown monkey cells, according to Science News.

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

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

Both drugs share a similar chemical structure that resembles a segment of viral RNA — molecules known as nucleotides that link up to form both RNA and DNA. When exposed to either drug, coronavirus enzymes wedge the molecule into the viral RNA in place of a true nucleotide, which brings viral replication to a standstill. Note that the drugs only work with RNA-virus enzymes, rather than human enzymes, so they don't mess up human DNA replication, according to the Scope Blog, published by Stanford Medicine.

A study published in the journal Cell Reports showed that, in addition to stopping feline coronavirus, GS-441524 can also keep SARS-CoV-2 from replicating in lab-grown monkey and human cells. However, GS-441524 was most effective in the monkey cells, while remdesivir worked better than GS-441524 in human lung cells, according to Science News.

The biopharmaceutical company Gilead Sciences designed both remdesivir and GS-441524 and has begun early studies to compare the effects of both drugs against SARS-CoV-2, company spokesperson Chris Ridley told Science News.

Previously, the company stated that it chose to focus on remdesivir over GS-441524 at the start of the pandemic because remdesivir had already been tested in human safety trials as an antiviral treatment for Ebola, which the drug didn't treat effectively, according to Science News. While testing remdesivir for Ebola, Gilead decided not to seek approval for GS-441524 use in animals because the drug so closely resembled remdesivir and may have somehow influenced the FDA-approval process, according to The Atlantic. Even now, GS-441524 has not been approved for use in cats and is usually bought as an expensive, black-market formulation, The Atlantic reported.

At this point, neither GS-441524 nor GC376 have been tested in humans at all.