James McKerrow, MD, PhD, dean of the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, has long studied neglected tropical diseases – chronic, crippling parasitic infections that primarily affect poor and underserved communities. developing countries.
They are called “neglected” because pharmaceutical companies have little financial incentive to develop therapies for them.
One of these neglected diseases is Chagas disease, the leading cause of heart failure in Latin America, which is spread by “kissing bugs” the parasite Trypanosoma cruzi. These parasites produce an enzyme called cruzain which helps them replicate and escape the human immune system. McKerrow’s research team is looking for cruzaïne inhibitors – small molecules that could form the basis of new antiparasitic drugs. A particularly effective cruzaïne inhibitor is called K777.
Then, in the spring of 2020, the Covid-19 pandemic began to sweep the United States. Researchers quickly reported that SARS-CoV-2, the coronavirus that causes Covid-19, cannot attach itself to and infect human cells unless a human enzyme called cathepsin L cleaves the spike protein of the virus.
And it turns out that cathepsin L looks and acts a lot like cruzain.
In a study published March 31, 2021 by ACS Chemical Biology, McKerrow and the team show that low concentrations of K777 inhibit cathepsin L may reduce the ability of SARS-CoV-2 to infect four host cell lines, without harming cells. .
“Since K777 inhibits a human enzyme, not the virus itself, we hope it is less likely that the virus will evolve against it,” said McKerrow, co-lead author of the study with Thomas Meek, PhD, of Texas A&M University.
K777 was not as effective in all cell lines. This is probably because not all cell lines produced the same amount of cathepsin L or the same amount of ACE2, the host cell receptor that the virus’s spike protein uses to attach itself to cells afterwards. have been cleaved by cathepsin L. -VOC-2 infection in cells that produced the most cathepsin L and ACE2.
The cell lines tested were derived from African green monkey renal epithelium, human cervical epithelium, and two types of human lung epithelium. Although this is an important research tool, such cell lines are not necessarily representative of patients. They are easy to grow and handle in research labs because they are cancer cells, but it also means that their molecular characteristics are likely to differ from the healthy lung or cervical cells of an average person.
“We were surprised at the effectiveness of K777 in blocking viral infections in the lab,” McKerrow said. “Yet, under usual circumstances, it would be impractical and unlikely for us ourselves to be able to get the compound so quickly through clinical trials. We are fortunate that an ‘entrepreneur-in-residence’ program here. at UC San Diego helped close that gap. “
Selva Therapeutics, a private biotechnology company, has licensed K777 to UC San Diego. Along with this study, the company also found that the experimental therapeutics prevented lung damage in Covid-19 animal models and was well tolerated by those who participated in the phase I clinical trial to assess safety. Selva plans a Phase II clinical trial in outpatient Covid-19 patients for the end of 2021.
Many people with Covid-19 suffer from mild illness and can recover at home with supportive care to help relieve their symptoms. Currently, severe cases of Covid-19 can be treated with the antiviral drug reissue, approved by the United States Food and Drug Administration (FDA) for use in hospital patients, or a drug that has been approved for use. emergency use of the FDA, such as the monoclonal. antibody.
More than 124 million people have been diagnosed with Covid-19 worldwide and 2.72 million have died from the infection.
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This story was posted from an agency feed with no text editing.