American scientists have developed a drug that prevents the reproduction of the parasite Trypanosoma cruzi, the causative agent of Chagas tropical disease. And it turns out that the drug effectively blocks SARS-CoV-2 replication.
American biologists led by Dr. James McIiro, dean of the Skaggs School of Pharmacy and Pharmaceutical Sciences at UCSD, have long studied neglected tropical diseases, such as chronic and disabling parasitic infections that primarily affect poor and disadvantaged communities in developing nations. Its name is “neglected” because there is little financial incentive for drug companies to develop treatments 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,” or vampire bugs, that carry the Trypanosoma cruzi (or Trypanosoma cruzi) parasite.
These parasites produce an enzyme called crane that helps them reproduce and evade the human immune system. Macero’s team is looking at kerosene inhibitors, small molecules that may form the basis for new anti-parasite drugs. And one particularly effective cruzine inhibitor is called K777.
Then, in the spring of 2020, the “Covid-19” pandemic began to sweep the world. The researchers report that SARS-CoV-2 cannot attach to and infect human cells unless a human enzyme called cathepsin L cleaves the viral “spike” protein.
And the cathepsin L happens to look and act very much like Crozen. And in a study published on March 31, 2021 by ACS Chemical Biology, Dr.Makeru and his team showed that low concentrations of K777 inhibiting cathepsin L can reduce the ability of SARS-CoV-2 to infect four lines of host cells, without damaging the cells.
“Since K777 inhibits a human enzyme, not the virus itself, we hope that the virus does not develop resistance against it,” said Maciro, co-senior author of the study with Dr. Thomas Meek, of A&M University in Texas.
K777 was not equally effective in all cell lines. This is likely because not all cell strains produced the same amount of cathepsin L or the same amount of ACE2, the host cell receptor that the virus spike protein uses to adhere to cells after its cleavage with cathepsin L. The inhibitor was best at preventing SARS-CoV-2. Novel coronavirus infection in cells that produce most of the cathepsin L and ACE2.
The cell lines tested were derived from kidney epithelium of African green monkey, human cervical epithelium and two types of human lung epithelium. Although an important research tool, cell lines such as these do not necessarily represent patients. But they are easy to grow and manipulate in research laboratories because they are cancer cells, and this also means that their molecular properties are likely to differ from a normal person’s lung or cervical cells.
“We were surprised at how effective K777 was at preventing viral infections in the laboratory. However, under normal circumstances, it would be impractical and unlikely that we ourselves would be able to transfer the compound so quickly to clinical trials. We are fortunate to have the Entrepreneur program. Here at UCSD, he helped fill that gap. ”
Selva Therapeutics, a private biotech company, licensed K777 from UCSD. In parallel with this study, the company also found that the experimental treatment prevented lung damage in animal models of “Covid-19” and was well tolerated by people who participated in a phase I clinical trial to assess safety. Selva plans to conduct a phase 1 clinical trial on out-of-hospital COVID-19 patients in late 2021.
Source: Medical Express