Yeast tests reveal potential drug leads for COVID and malaria

A Faroese researcher has used ordinary yeast and an automated laboratory robot to identify compounds that could lead to treatments for COVID-19 and malaria. KVF reports that Sunniva Sigurdardóttir carried out the work for her PhD at the University of Gothenburg.

Developing medicines for infectious diseases often involves costly and potentially dangerous work with live viruses and parasites. Sigurdardóttir instead used Saccharomyces cerevisiae, a yeast that is easy to grow, reproduces quickly and is not harmful. Although yeast and humans diverged more than a billion years ago, their cells share many basic biological processes and thousands of genes.

Researchers genetically modified the yeast to resemble human cells, allowing them to test how compounds affected particular proteins. Sigurdardóttir began her PhD work in 2020, when COVID-19 emerged. Her team focused on Mpro, an enzyme SARS-CoV-2 needs to spread.

The researchers built a genetic “trap” using a bacterial toxin and antitoxin. When the viral enzyme was active, it released the toxin and killed the yeast. If a compound blocked the enzyme, the yeast survived. Robot Eve screened thousands of compounds automatically, helping the team identify some with potential for future medicines and rule out others that did not affect the enzyme.

The later part of the research focused on malaria, as parasites can develop resistance to existing medicines. The team studied Plasmodium vivax, which can hide in the liver for months or years, and examined its DHS enzyme. They replaced the yeast’s own enzyme with either human DHS or the parasite’s version, allowing them to compare the effects of compounds on each.

Of 200,000 compounds tested, three affected the parasite protein but not the human protein, Sigurdardóttir said. The findings suggest these compounds could potentially be developed into treatments targeting P. vivax.

Sigurdardóttir said medicines remain necessary even when vaccines are available because not everyone is vaccinated and vaccine protection can weaken over time. Developing a compound into a finished medicine typically takes 10 to 15 years, but the yeast-based method could make the early screening stage cheaper, faster and more precise.