32NU
Crystal structure of SARS-CoV-2 Mpro in complex with NSC47924
This is a non-PDB format compatible entry.
Summary for 32NU
| Entry DOI | 10.2210/pdb32nu/pdb |
| Descriptor | 3C-like proteinase nsp5, 1-[[(4-methoxyphenyl)amino]methyl]naphthalen-2-ol (3 entities in total) |
| Functional Keywords | inhibitor, mpro, complex, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 1 |
| Total formula weight | 34104.88 |
| Authors | |
| Primary citation | Akrani, I.,El Kilani, H.,Touret, F.,Kouvali, S.,Gourni, V.,Tsoka, A.,Tsetis, J.K.,Vorgias, C.,Hilgenfeld, R.,Kostakis, I.K.,Myrianthopoulos, V.,Mikros, E. Investigating the Binding Mode of a Naphthol-Based Inhibitor Targeting SARS-CoV-2 Main Protease. Chemmedchem, 21:e70448-e70448, 2026 Cited by PubMed Abstract: Regardless of the massive global efforts to combat the virus causing SARS-CoV-2 syndrome, the infection remains a substantial health challenge worldwide in the years following 2019. To this direction, targeting the main viral protease M has been proposed as a tractable and particularly promising approach toward developing effective and safe COVID-19 antivirals. By applying an integrated workflow combining a previously developed in silico consensus ranking protocol with two orthogonal in vitro methods, the NCI/DTP repository is screened and the discovery of an original naphthol scaffold with M inhibitory properties is reported. The hit is characterized in terms of structure and binding thermodynamics by combining X-ray crystallography and isothermal titration calorimetry where a binding affinity constant of 1.55 μM is determined. The compound is further evaluated against virus-infected cells, where an EC value of 7.23 μM and comparable toxicity with nirmatrelvir are measured. Chemical synthesis is additionally employed to facilitate optimal exploration of the structure-activity relationship landscape regarding the new hit. By integrating computational, biophysical, and enzymatic methods, the suggested approach allows the combination of a structural hypothesis with functional evidence and shows its capacity toward identifying and rationally optimizing structurally original noncovalent M inhibitors. PubMed: 42647061DOI: 10.1002/cmdc.70448 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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