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| Home > Publications database > Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L > print |
| 001 | 902158 | ||
| 005 | 20240625095110.0 | ||
| 024 | 7 | _ | |a 10.3390/ijms222111779 |2 doi |
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| 100 | 1 | _ | |a Costanzi, Elisa |b 0 |
| 245 | _ | _ | |a Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L |
| 260 | _ | _ | |a Basel |c 2021 |b Molecular Diversity Preservation International |
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| 520 | _ | _ | |a After almost two years from its first evidence, the COVID-19 pandemic continues to afflict people worldwide, highlighting the need for multiple antiviral strategies. SARS-CoV-2 main protease (Mpro/3CLpro) is a recognized promising target for the development of effective drugs. Because single target inhibition might not be sufficient to block SARS-CoV-2 infection and replication, multi enzymatic-based therapies may provide a better strategy. Here we present a structural and biochemical characterization of the binding mode of MG-132 to both the main protease of SARS-CoV-2, and to the human Cathepsin-L, suggesting thus an interesting scaffold for the development of double-inhibitors. X-ray diffraction data show that MG-132 well fits into the Mpro active site, forming a covalent bond with Cys145 independently from reducing agents and crystallization conditions. Docking of MG-132 into Cathepsin-L well-matches with a covalent binding to the catalytic cysteine. Accordingly, MG-132 inhibits Cathepsin-L with nanomolar potency and reversibly inhibits Mpro with micromolar potency, but with a prolonged residency time. We compared the apo and MG-132-inhibited structures of Mpro solved in different space groups and we identified a new apo structure that features several similarities with the inhibited ones, offering interesting perspectives for future drug design and in silico efforts. |
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| 700 | 1 | _ | |a Kuzikov, Maria |0 0000-0001-8771-1865 |b 1 |
| 700 | 1 | _ | |a Esposito, Francesca |0 0000-0001-9725-7977 |b 2 |
| 700 | 1 | _ | |a Albani, Simone |0 P:(DE-Juel1)181061 |b 3 |
| 700 | 1 | _ | |a Demitri, Nicola |b 4 |
| 700 | 1 | _ | |a Giabbai, Barbara |b 5 |
| 700 | 1 | _ | |a Camasta, Marianna |b 6 |
| 700 | 1 | _ | |a Tramontano, Enzo |0 0000-0002-4849-0980 |b 7 |
| 700 | 1 | _ | |a Rossetti, Giulia |0 P:(DE-Juel1)145921 |b 8 |e Corresponding author |
| 700 | 1 | _ | |a Zaliani, Andrea |0 0000-0002-1740-8390 |b 9 |
| 700 | 1 | _ | |a Storici, Paola |0 P:(DE-HGF)0 |b 10 |e Corresponding author |
| 773 | _ | _ | |a 10.3390/ijms222111779 |g Vol. 22, no. 21, p. 11779 - |0 PERI:(DE-600)2019364-6 |n 21 |p 11779 - |t International journal of molecular sciences |v 22 |y 2021 |x 1422-0067 |
| 856 | 4 | _ | |u https://juser.fz-juelich.de/record/902158/files/ijms-22-11779-v2.pdf |y OpenAccess |
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