Two compounds reduce Cryptosporidium parasites in mice and calves

Cryptosporidium parvum and Cryptosporidium hominis are a pair of parasites that infect the small intestine and cause diarrhea in humans. Researchers have identified two new compounds that reduce the number of C. parvum parasites in mice and calves (Sci. Transl. Med. 2024, DOI: 10.1126/scitranslmed.adm8631).

The team originally identified a series of compounds that work against Plasmodium falciparum, the predominant malaria-causing parasite in people. Those compounds targeted lysyl-tRNA synthetase, an enzyme that helps P. falciparum produce proteins. Researchers discovered that one of the compounds also inhibited the lysyl-tRNA synthetase of C. parvum parasites, but they deemed the compound’s toxicity in mice unsuitable.

The scientists then designed C. parvum lysyl-tRNA synthetase–targeting compounds with partially restricted absorption across the gastrointestinal tract. They predicted that such compounds could be more effective against Cryptosporidium parasites and less toxic.

The team identified two lead compounds that reduced the number of parasites in immunocompromised mice infected with C. parvum. When they tested the two compounds in calves—which unlike mice show clinical symptoms when infected with C. parvum—the animals receiving the compounds had reduced diarrhea and numbers of parasites compared with calves in the control group.

Robert Gilman, a professor of public health at the Johns Hopkins Bloomberg School of Public Health who was not involved in the research, writes in an email that the study is an “interesting start” but that further efficacy and toxicity work is needed.