TY - JOUR
AU - Canal, Berta
AU - Fujisawa, Ryo
AU - McClure, Allison W.
AU - Deegan, Tom D.
AU - Wu, Mary
AU - Ulferts, Rachel
AU - Weissmann, Florian
AU - Drury, Lucy S.
AU - Bertolin, Agustina P.
AU - Zeng, Jingkun
AU - Beale, Rupert
AU - Howell, Michael
AU - Labib, Karim
AU - Diffley, John F. X.
PY - 2021
DA - July
TI - Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp15 endoribonuclease
JO - Biochemical Journal
EP - 2479
VL - 478
IS - 13
DO - https://doi.org/10.1042/BCJ20210199
AB - SARS-CoV-2 is responsible for COVID-19, a human disease that has caused over 2 million deaths, stretched health systems to near-breaking point and endangered economies of countries and families around the world. Antiviral treatments to combat COVID-19 are currently lacking. Remdesivir, the only antiviral drug approved for the treatment of COVID-19, can affect disease severity, but better treatments are needed. SARS-CoV-2 encodes 16 non-structural proteins (nsp) that possess different enzymatic activities with important roles in viral genome replication, transcription and host immune evasion. One key aspect of host immune evasion is performed by the uridine-directed endoribonuclease activity of nsp15. Here we describe the expression and purification of nsp15 recombinant protein. We have developed biochemical assays to follow its activity, and we have found evidence for allosteric behaviour. We screened a custom chemical library of over 5000 compounds to identify nsp15 endoribonuclease inhibitors, and we identified and validated NSC95397 as an inhibitor of nsp15 endoribonuclease in vitro. Although NSC95397 did not inhibit SARS-CoV-2 growth in VERO E6 cells, further studies will be required to determine the effect of nsp15 inhibition on host immune evasion.
PB - Portland Press
UR - https://discovery.dundee.ac.uk/en/publications/a2f640ae-33a8-44bb-9c81-a5e83fbfa133
KW - Coronavirus (COVID-19)
ER