TY - JOUR
AU - Canal, Berta
AU - McClure, Allison W.
AU - Curran, J.
AU - Wu, Mary
AU - Ulferts, Rachel
AU - Weissmann, Florian
AU - Zeng, Jingkun
AU - Bertolin, Agustina P.
AU - Milligan, Jennifer C.
AU - Basu, Souradeep
AU - Drury, Lucy S.
AU - Deegan, Tom D.
AU - Fujisawa, Ryo
AU - Roberts, Emma L.
AU - Basier, Clovis
AU - Labib, Karim
AU - Beale, Rupert
AU - Howell, Michael
AU - Diffley, John F. X.
PY - 2021
DA - April
TI - Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp14/nsp10 Exoribonuclease
JO - Biochemical Journal
EP - 2464
VL - 478
IS - 13
DO - https://doi.org/10.1101/2021.04.07.438812
AB - 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 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 high-throughput 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.
PB - Portland Press
UR - https://discovery.dundee.ac.uk/en/publications/406d609f-ff8a-4237-b61c-6e43bee0f853
KW - Coronavirus (COVID-19)
ER