A repurposed drug screen identifies compounds that inhibit the binding of the COVID-19 spike protein to ACE2
| Autor: | Kaleb B. Tsegay, Christiana M. Adeyemi, Edward P. Gniffke, D. Noah Sather, John K. Walker, Stephen E. P. Smith |
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| Rok vydání: | 2021 |
| Předmět: |
Drug
Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) media_common.quotation_subject RM1-950 inhibition assay drug screen Thiostrepton Article law.invention repurposed chemistry.chemical_compound law medicine Pharmacology (medical) Receptor IC50 media_common Pharmacology Chemistry Drug discovery COVID-19 Spike Protein Brief Research Report Nilotinib Biochemistry Docking (molecular) IP-FCM Recombinant DNA Therapeutics. Pharmacology hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | bioRxiv Frontiers in Pharmacology, Vol 12 (2021) Frontiers in Pharmacology |
| Popis: | Repurposed drugs that block the interaction between the SARS-CoV-2 spike protein and its receptor ACE2 could offer a rapid route to novel COVID-19 treatments or prophylactics. Here, we screened 2,701 compounds from a commercial library of drugs approved by international regulatory agencies for their ability to inhibit the binding of recombinant, trimeric SARS-CoV-2 spike protein to recombinant human ACE2. We identified 56 compounds that inhibited binding in a concentration-dependent manner, measured the IC50of binding inhibition, and computationally modeled the docking of the best inhibitors to the Spike-ACE2 binding interface. The best candidates were Thiostrepton, Oxytocin, Nilotinib, and Hydroxycamptothecin with IC50’s in the 4–9 μM range. These results highlight an effective screening approach to identify compounds capable of disrupting the Spike-ACE2 interaction, as well as identify several potential inhibitors of the Spike-ACE2 interaction. |
| Databáze: | OpenAIRE |
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