期刊
BIOCHEMICAL JOURNAL
卷 478, 期 1, 页码 2445-2464出版社
PORTLAND PRESS LTD
DOI: 10.1042/BCJ20210198
关键词
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资金
- Francis Crick Institute from Cancer Research U.K. [FC001066]
- U.K. Medical Research Council [FC001066]
- Wellcome Trust [FC001066]
- Wellcome Trust Senior Investigator Award [106252/Z/14/Z]
- Boehringer Ingelheim Fonds
- European Union [895786, 844211]
- Wellcome Trust under the Sir Henry Wellcome Postdoctoral Fellowship [204678/Z/16/Z]
- Wellcome Trust [106252/Z/14/Z, 204678/Z/16/Z] Funding Source: Wellcome Trust
- Marie Curie Actions (MSCA) [844211] Funding Source: Marie Curie Actions (MSCA)
SARS-CoV-2, a novel coronavirus, has caused a global pandemic with severe social and economic consequences. Researchers have identified new antiviral compounds, such as patulin and ATA, which can effectively inhibit the replication of SARS-CoV-2, providing new therapeutic possibilities for COVID-19 treatment.
SARS-CoV-2 is a coronavirus that emerged in 2019 and rapidly spread across the world causing a deadly pandemic with tremendous social and economic costs. Healthcare systems worldwide are under great pressure, and there is an urgent need for effective antiviral treatments. The only currently approved antiviral treatment for COVID-19 is remdesivir, an inhibitor of viral genome replication. SARS-CoV-2 proliferation relies on the enzymatic activities of the non-structural proteins (nsp), which makes them interesting targets for the development of new antiviral treatments. With the aim to identify novel SARS-CoV-2 antivirals, we have purified the exoribonuclease/methyltransferase (nsp14) and its cofactor (nsp10) and developed biochemical assays compatible with highthroughput approaches to screen for exoribonuclease inhibitors. We have screened a library of over 5000 commercial compounds and identified patulin and aurintricarboxylic acid (ATA) as inhibitors of nsp14 exoribonuclease in vitro. We found that patulin and ATA inhibit replication of SARS-CoV-2 in a VERO E6 cell-culture model. These two new antiviral compounds will be valuable tools for further coronavirus research as well as potentially contributing to new therapeutic opportunities for COVID-19.
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