Definition: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
Input: Coronaviral infection is associated with up to 5% of respiratory tract diseases. The 3C-like protease (3CL pro ) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection. We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CL pro of severe-acute-respiratory-syndrome-coronavirus. The IC 50 values of the inhibitors were in the range of 4.6e49 mM, demonstrating that the nitrile warhead can effectively inactivate the 3CL pro autocleavage process. The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was w10x more potent than the other inhibitors tested. Crystal structures of the enzymeeinhibitor complexes showed that the nitrile warhead inhibits 3CL pro by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1eS4 substratebinding pockets. We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broadspectrum inhibition against 3CL pro from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC 50 values ranging from 1.3 to 3.7 mM, but no detectable inhibition against caspase-3. In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CL pro , and they inhibit 3CL pro from a broad range of coronaviruses. Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection.

Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases