2. Academic Validation
  3. Potent in vitro anti-SARS-CoV-2 activity by gallinamide A and analogues via inhibition of cathepsin L

Potent in vitro anti-SARS-CoV-2 activity by gallinamide A and analogues via inhibition of cathepsin L

  • bioRxiv. 2020 Dec 24;2020.12.23.424111. doi: 10.1101/2020.12.23.424111.
Anneliese S Ashhurst,  Arthur H Tang,  Pavla Fajtová,  Michael Yoon,  Anupriya Aggarwal,  Alexander Stoye,  Mark Larance,  Laura Beretta,  Aleksandra Drelich,  Danielle Skinner,  Linfeng Li,  Thomas D Meek,  James H McKerrow,  Vivian Hook,  Chien-Te K Tseng,  Stuart Turville,  William H Gerwick,  Anthony J O'Donoghue,  Richard J Payne
PMID: 33398273 DOI: 10.1101/2020.12.23.424111
Abstract

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 IC 50 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 EC 50 values in the nanomolar range, thus further highlighting the potential of Cathepsin L as a COVID-19 Antiviral drug target.

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