Scientists at the University of California at San Diego and at A&M University in Texas, both in the United States, have been studying it as an experimental therapy for Chagas’ disease because it is useful in also containing the infection caused by Sars-CoV-2, a virus that causes Covid-19. In a study published on March 31 in the journal ACS Chemical Biology, the team presented the most recent (and encouraging) findings of the undertaking.
Chagas disease is the leading cause of heart failure in Latin America. It is classified as one of the neglected tropical diseases, those that, because they reach mostly poorer countries, receive little attention and investment from the pharmaceutical industry and international research. The disease is caused by the parasite Trypanosoma cruzi, whose main vector for humans is the bed bug popularly known as barber.
Once in our body, the Trypanosoma cruzi produces an enzyme called cruzaine, which allows it to replicate and invade the immune system. Researchers in the United States are studying an inhibitor for this enzyme that can be used in an eventual medication. With the Covid-19 pandemic, the team tried to use the findings of this research in order to fight the new coronavirus.
Even at the beginning of the spread of Sars-CoV-2 by the United States, experts observed that the virus can only infect human cells if its protein spike is cleaved by an enzyme called cathepsin L. And that enzyme is very similar to cruzaine, according to the authors.
In the new study, the team demonstrated – from cells created in the laboratory – that an inhibitor that has already been shown to be effective against cruzaine, K777, is also capable of inhibiting cathepsin L. Thus, Sars-CoV-2 does not can infect the cells. “Since K777 inhibits a human enzyme, not the virus itself, we expect the virus to be less likely to develop resistance against it,” comments James McKerrow, senior co-author of the study, in a note.
K777 did a better job of preventing infection by the new coronavirus in those cell structures that produce cathepsin L and ACE2, an enzyme that works just as a receptor for the protein spike of the virus that causes Covid-19. “We were surprised by the effectiveness of K777 in blocking viral infection in the laboratory,” says McKerrow.
In parallel to this work, Selva Therapeutics, an American biotechnology company, licensed the K777 and found, in animal studies, that the inhibitor helps prevent lung damage caused by Covid-19. Promising results have also been obtained in a phase 1 clinical trial. The first phase of phase 2, with outpatients, is expected to happen at the end of 2021.
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