Project Grant R01AI201768

The National Institute of Allergy and Infectious Diseases awarded Colorado State University $2,036,679 on September 3, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to conduct high-throughput screening and characterization of small-molecule inhibitors targeting N-terminal autoproteolysis of coronavirus main protease precursors.

The recipient will develop and execute cell-based assays to identify compounds that selectively interfere with precursor-mediated autoproteolysis in SARS-CoV-2 and MERS-CoV main proteases. The research builds on prior work demonstrating that coronavirus main protease precursor forms exhibit markedly reduced sensitivity to inhibitors designed for mature enzymes. The team will conduct pilot screens of known protease inhibitors and natural product extracts to validate assay robustness and identify novel hits with activity against both wild-type and drug-resistant variants, extending a validated precursor autoproteolysis strategy previously demonstrated in HIV-1 protease research.

Work is performed in Fort Collins, Colorado. The period of performance runs through August 31, 2030. Colorado State University's Sponsored Programs division, the research contracting arm of the institution, serves as the prime recipient.