Inhibition principles of the SARS-CoV-2 proteases
Inhibition principles of the SARS-CoV-2 proteases
Disciplines
Biology (20%); Chemistry (30%); Health Sciences (40%); Medical Engineering (10%)
Keywords
-
SARS-CoV-2 proteases,
3CLpro,
PLpro,
Inhibition
Proteases are enzymes that process large proteins into smaller ones. They play a critical role in the replication cycle of several viruses. Therapeutics of Human Immunodeficiency Virus or Hepatitis C Virus (HCV) inhibit the proteases of these viruses. Coronaviruses also have two such proteases. So fa r, only few substances are known, which can inhibit these proteases. One of them is licensed to treat HCV. A new screening method, which was developed by Emmanuel Heilmann from the research group of Dorothee von Laer at the Medical University of Innsbruck, can measure the earliest activity of the SARS- CoV-2 proteases. With this method, especially effective compounds can be found to stop the replication of Coronaviruses. The method allows to test the inhibition efficiency, the cell permeability and even the toxicity at once. This combined read-out saves valuable time in developing therapeutics.
- Janine Kimpel, Medizinische Universität Innsbruck , national collaboration partner
- Hubert Gstach, national collaboration partner
- Alexander Kurt Hermann Weiss, Universität Innsbruck , national collaboration partner
Research Output
- 333 Citations
- 9 Publications
-
2024
Title Vesicular Stomatitis Virus as a Platform for Protease Activity Measurements DOI 10.1002/cpz1.70062 Type Journal Article Author Rauch S Journal Current Protocols Link Publication -
2024
Title A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system DOI 10.1371/journal.ppat.1012522 Type Journal Article Author Costacurta F Journal PLOS Pathogens Link Publication -
2024
Title Using Vesicular Stomatitis Virus as a Platform for Directed Protease Evolution DOI 10.1002/cpz1.70074 Type Journal Article Author Costacurta F Journal Current Protocols Link Publication -
2023
Title A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system DOI 10.1101/2023.09.22.558628 Type Preprint Author Costacurta F Pages 2023.09.22.558628 Link Publication -
2024
Title Highly specific SARS-CoV-2 main protease (Mpro) mutations against the clinical antiviral ensitrelvir selected in a safe, VSV-based system DOI 10.1016/j.antiviral.2024.105969 Type Journal Article Author Rauch S Journal Antiviral Research Pages 105969 Link Publication -
2024
Title Study of key residues in MERS-CoV and SARS-CoV-2 main proteases for resistance against clinically applied inhibitors nirmatrelvir and ensitrelvir DOI 10.1038/s44298-024-00028-2 Type Journal Article Author Krismer L Journal npj Viruses Pages 23 Link Publication -
2023
Title Identification of key residues in MERS-CoV and SARS-CoV-2 main proteases for resistance against clinically applied inhibitors nirmatrelvir and ensitrelvir DOI 10.1101/2023.12.04.569917 Type Preprint Author Krismer L Pages 2023.12.04.569917 Link Publication -
2023
Title Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors DOI 10.1126/sciadv.ade8778 Type Journal Article Author Moghadasi S Journal Science Advances Link Publication -
2023
Title SARS-CoV-2 3CLpro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376 DOI 10.1126/scitranslmed.abq7360 Type Journal Article Author Heilmann E Journal Science Translational Medicine Link Publication