Characterisation of ten NS2B-NS3 proteases: Paving the way for pan-flavivirus drugs

In this study, we characterised recombinant NS2B-NS3 proteases from ten flaviviruses including three unreported proteases from the Usutu, Kyasanur forest disease and Powassan viruses. All protease constructs comprise a covalent Gly4-Ser-Gly4 linker connecting the NS3 serine protease domain with its cofactor NS2B. We conducted a comprehensive cleavage site analysis revealing areas of high conversion. While all proteases were active in enzymatic assays, we noted a 1000-fold difference in catalytic efficiency across proteases from different flaviviruses. Two bicyclic peptide inhibitors displayed anti-pan-flaviviral protease activity with inhibition constants ranging from 10 to 1000 nM.PMID:38582134 | DOI:10.1016/j.antiviral.2024.105878

Source: Antiviral Research - April 6, 2024 Category: Virology Authors: Saan Voss J örg Rademann Christoph Nitsche Source Type: research