Stabilization of the Dimeric State of SARS-CoV-2 Main Protease by GC376 and Nirmatrelvir

• Published in: International journal of molecular sciences Vol. 24; no. 7; p. 6062
• Main Authors: Paciaroni, Alessandro, Libera, Valeria, Ripanti, Francesca, Orecchini, Andrea, Petrillo, Caterina, Francisci, Daniela, Schiaroli, Elisabetta, Sabbatini, Samuele, Gidari, Anna, Bianconi, Elisa, Macchiarulo, Antonio, Hussain, Rohanah, Silvestrini, Lucia, Moretti, Paolo, Belhaj, Norhan, Vercelli, Matteo, Roque, Yessica, Mariani, Paolo, Comez, Lucia, Spinozzi, Francesco
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.03.2023; MDPI
• Subjects: Antiviral activity; Antiviral agents; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Binding; Binding sites; Bioavailability; Catalytic activity; Coronaviridae; Coronaviruses; COVID-19; COVID-19 vaccines; Cysteine Endopeptidases - metabolism; Dimerization; Drug development; Drugs; Enzymes; Equilibrium; Feline infectious peritonitis; Health aspects; Humans; Hydrogen; Hydrogen bonding; Hydrogen bonds; Infections; inhibitor; Inhibitors; Ligands; main protease; Middle East respiratory syndrome; Molecular Docking Simulation; Paxlovid; Peritonitis; Polyproteins; Protease; Protease Inhibitors - chemistry; Protease Inhibitors - pharmacology; Proteases; Proteinase; Proteinase inhibitors; Proteins; Respiratory diseases; SARS-CoV-2; SARS-CoV-2 - metabolism; Severe acute respiratory syndrome coronavirus 2; Germany; Middle East; COVID-19; Paxlovid; SARS-CoV-2; inhibitor; main protease; dimerization; microscale thermophoresis; circular dichroism; PF-07321332; small angle X-ray scattering

The main protease (Mpro or 3CLpro) is an enzyme that is evolutionarily conserved among different genera of coronaviruses. As it is essential for processing and maturing viral polyproteins, Mpro has been identified as a promising target for the development of broad-spectrum drugs against coronaviruse...