7NT4
X-ray structure of SCoV2-PLpro in complex with small molecule inhibitor
Summary for 7NT4
| Entry DOI | 10.2210/pdb7nt4/pdb |
| Descriptor | Non-structural protein 3, PROFLAVIN, 1,2-ETHANEDIOL, ... (6 entities in total) |
| Functional Keywords | drug repurposing, scov2-plpro inhibitor, hydrolase |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) |
| Total number of polymer chains | 2 |
| Total formula weight | 74162.75 |
| Authors | Napolitano, V.,Mourao, A.,Bostock, M.,Matsuda, A.,Czarna, A.,Popowicz, G.M. (deposition date: 2021-03-09, release date: 2022-02-02, Last modification date: 2024-11-06) |
| Primary citation | Napolitano, V.,Dabrowska, A.,Schorpp, K.,Mourao, A.,Barreto-Duran, E.,Benedyk, M.,Botwina, P.,Brandner, S.,Bostock, M.,Chykunova, Y.,Czarna, A.,Dubin, G.,Frohlich, T.,Holscher, M.,Jedrysik, M.,Matsuda, A.,Owczarek, K.,Pachota, M.,Plettenburg, O.,Potempa, J.,Rothenaigner, I.,Schlauderer, F.,Slysz, K.,Szczepanski, A.,Greve-Isdahl Mohn, K.,Blomberg, B.,Sattler, M.,Hadian, K.,Popowicz, G.M.,Pyrc, K. Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses. Cell Chem Biol, 29:774-, 2022 Cited by PubMed Abstract: The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PL) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PL catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks. PubMed: 35021060DOI: 10.1016/j.chembiol.2021.11.006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.68 Å) |
Structure validation
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