Identification of Potent Small Molecule Inhibitors of SARS-CoV-2 Entry
ABSTRACT 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..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 25. Mai Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mediouni, Sonia [VerfasserIn] |
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| Links: |
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| doi: |
10.1101/2021.08.05.455262 |
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| PPN (Katalog-ID): |
XBI032343825 |
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| 520 | |a ABSTRACT 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. | ||
| 700 | 1 | |a Mou, Huihui |e verfasserin |4 aut | |
| 700 | 1 | |a Otsuka, Yuka |e verfasserin |4 aut | |
| 700 | 1 | |a Jablonski, Joseph Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Adcock, Robert Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Batra, Lalit |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Dong-Hoon |e verfasserin |4 aut | |
| 700 | 1 | |a Rood, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a de Vera, Ian Mitchelle S. |e verfasserin |4 aut | |
| 700 | 1 | |a Rahaim, Ronald |e verfasserin |4 aut | |
| 700 | 1 | |a Ullah, Sultan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xuerong |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Tu-Trinh |e verfasserin |4 aut | |
| 700 | 1 | |a Hull, Mitchell |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Emily |e verfasserin |4 aut | |
| 700 | 1 | |a Bannister, Thomas D. |e verfasserin |4 aut | |
| 700 | 1 | |a Baillargeon, Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Scampavia, Louis |e verfasserin |4 aut | |
| 700 | 1 | |a Farzan, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Valente, Susana T. |e verfasserin |4 aut | |
| 700 | 1 | |a Spicer, Timothy P. |e verfasserin |4 aut | |
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