AI Article Synopsis
- Foot-and-mouth disease virus (FMDV) is highly contagious and causes severe economic losses in livestock.
- The viral genome is processed into functional proteins mainly by a crucial enzyme called the 3C protease, which is a promising target for developing antiviral drugs.
- Researchers have created irreversible inhibitors by modifying a peptide to improve its interaction with the protease, revealing that a positively charged component is key to enhancing drug effectiveness.
Article Abstract
Foot-and-mouth disease virus (FMDV) causes a highly infectious and economically devastating disease of livestock. The FMDV genome is translated as a single polypeptide precursor that is cleaved into functional proteins predominantly by the highly conserved viral 3C protease, making this enzyme an attractive target for antiviral drugs. A peptide corresponding to an optimal substrate has been modified at the C-terminus, by the addition of a warhead, to produce irreversible inhibitors that react as Michael acceptors with the enzyme active site. Further investigation highlighted key structural determinants for inhibition, with a positively charged P2 being particularly important for potency.
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| http://dx.doi.org/10.1016/j.bmcl.2013.12.045 | DOI Listing |
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