| Autor: |
Richard J. Payne, William H. Gerwick, Michael Yoon, Alexander Stoye, James H. McKerrow, Pavla Fajtová, Laura Beretta, Stuart Turville, Aleksandra Drelich, Vivian Hook, Anthony J. O’Donoghue, Chien-Te K Tseng, Danielle E. Skinner, Anneliese S. Ashhurst, Thomas D. Meek, Anupriya Aggarwal, Mark Larance, Arthur H Tang, Linfeng Li |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
The emergence of SARS-CoV-2 in late 2019, and the subsequent COVID-19 pandemic, has led to substantial mortality, together with mass global disruption. There is an urgent need for novel antiviral drugs for therapeutic or prophylactic application. Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is recognized as a promising drug target. The marine natural product, gallinamide A and several synthetic analogues, were identified as potent inhibitors of cathepsin L activity with IC50 values in the picomolar range. Lead molecules possessed selectivity over cathepsin B and other related human cathepsin proteases and did not exhibit inhibitory activity against viral proteases Mpro and PLpro. We demonstrate that gallinamide A and two lead analogues potently inhibit SARS-CoV-2 infection in vitro, with EC50 values in the nanomolar range, thus further highlighting the potential of cathepsin L as a COVID-19 antiviral drug target. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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