New Therapy for Parasitic Disease may Help Fight Coronavirus

Chemical inhibitor K777 found to reduce the coronavirus' ability to infect cell lines by blocking human enzyme cathepsin L.

SARS-CoV-2, the coronavirus that causes COVID-19, can't dock on and infect human cells unless a human enzyme called cathepsin L cleaves the virus' spike protein.

Trypanosoma cruzi, the parasite that produce an enzyme called cruzain, helps them to replicate in humans. McKerrow's research team started looking for inhibitors of cruzain. One particularly effective cruzain inhibitor is called K777.

‘K777 inhibitors may hold promise in combatting coronavirus. Also, they inhibit human enzyme, not the virus itself. So, its less likely the virus will develop resistance against it.’
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They later found that cathepsin L looks and acts like cruzain.

In a study published by ACS Chemical Biology, McKerrow and the team show that low concentrations of K777 inhibit cathepsin L can reduce SARS-CoV-2's ability to infect four host cell lines, without harming the cells.

"Since K777 inhibits a human enzyme, not the virus itself, it's our hope that it's less likely the virus will evolve resistance against it," said McKerrow, co-senior author of the study with Thomas Meek, PhD, of Texas A&M University.

Coronavirus
Coronaviruses infect animals, humans, and birds. Human coronaviruses, such as SARS, MERS, and 2019-nCoV cause respiratory distress and even death. The S protein is the infectious agent of the virus.

The cell lines tested were derived from African green monkey kidney epithelium, human cervical epithelium and two types of human lung epithelium. While an important research tool, cell lines such as these are not necessarily representative of patients.

They are easy to grow and manipulate in research laboratories because they are cancer cells, but that also means their molecular features likely differ from the average person's healthy lung or cervical cells.

"We were surprised at just how effective K777 is in blocking viral infection in the lab," McKerrow said. "Yet under usual circumstances, it would be impractical and unlikely that we ourselves would be able to move the compound so quickly into clinical trials.

We're fortunate that an 'entrepreneur-in-residence' program here at UC San Diego has helped bridge that gap."

Selva Therapeutics has licensed K777 from UC San Diego. The company has also found that the experimental therapeutic prevented lung damage in COVID-19 animal models and was well-tolerated by people who participated in Phase I clinical trial to assess safety.

Selva is planning Phase II clinical trial in non-hospitalized COVID-19 patients for late 2021.

Source-Medindia