{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T15:35:05Z","timestamp":1768491305124,"version":"3.49.0"},"posted":{"date-parts":[[2020,12,25]]},"group-title":"Biochemistry","reference-count":63,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T00:00:00Z","timestamp":1608854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:sub>50<\/jats:sub>\n                  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\n                  <jats:italic>in vitro<\/jats:italic>\n                  , with EC\n                  <jats:sub>50<\/jats:sub>\n                  values in the nanomolar range, thus further highlighting the potential of cathepsin L as a COVID-19 antiviral drug target.\n                <\/jats:p>","DOI":"10.1101\/2020.12.23.424111","type":"posted-content","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T05:00:15Z","timestamp":1608872415000},"source":"Crossref","is-referenced-by-count":7,"title":["Potent\n                  <i>in vitro<\/i>\n                  anti-SARS-CoV-2 activity by gallinamide A and analogues via inhibition of cathepsin L"],"prefix":"10.64898","author":[{"given":"Anneliese S.","family":"Ashhurst","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur H.","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavla","family":"Fajtov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anupriya","family":"Aggarwal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Stoye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Larance","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Beretta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Drelich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Skinner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linfeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas D.","family":"Meek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James H.","family":"McKerrow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian","family":"Hook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Te K.","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Turville","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William H.","family":"Gerwick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J.","family":"O\u2019Donoghue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Payne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024080506122310000_2020.12.23.424111v1.1","unstructured":"World Health Organization, WHO Director-General\u2019s opening remarks at the media briefing on COVID-19. 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