Identification of Potent Small Molecule Inhibitors of SARS-CoV-2 Entry
| Autor: | Pierre Baillargeon, Huihui Mou, S. Valente, Thomas D. Bannister, S. Jablonski, Timothy P. Spicer, Louis Scampavia, Lalit Batra, Michael Farzan, Christopher Rood, Tu-Trinh Nguyen, Mitchell V. Hull, J. Jablonski, Robert S. Adcock, Donghoon Chung, Emily Chen, X. Yu, Sultan Ullah, R. Rahaim, I. M. de Vera, Yuka Otsuka |
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| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
Infectivity Protease Coronavirus disease 2019 (COVID-19) viruses Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) medicine.medical_treatment fungi virus diseases Biology Virology Small molecule body regions Enzyme chemistry Viral entry medicine Identification (biology) skin and connective tissue diseases |
| DOI: | 10.1101/2021.08.05.455262 |
| Popis: | The severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells. We report the identification of such inhibitors through a robust high-throughput screen testing 15,000 small molecules from unique libraries. Several leads were validated in a suite of mechanistic assays, including whole cell SARS-CoV-2 infectivity assays. The main lead compound, Calpeptin, was further characterized using SARS-CoV-1 and the novel SARS-CoV-2 variant entry assays, SARS-CoV-2 protease assays and molecular docking. This study reveals Calpeptin as a potent and specific inhibitor of SARS-CoV-2 and some variants. |
| Databáze: | OpenAIRE |
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