The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery
Open accessAbstract
SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease (PLpro) has been implicated in playing important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses. The multiple functions of PLpro render it a promising drug target. Therefore, we screened a library of approved drugs and also examined available inhibitors against PLpro. Inhibitor GRL0617 showed a promising in vitro IC 50 of 2.1 μM and an effective antiviral inhibition in cell-based assays. The co-crystal structure of SARS-CoV-2 PLpro C111S in complex with GRL0617 indicates that GRL0617 is a non-covalent inhibitor and it resides in the ubiquitin-specific proteases (USP) domain of PLpro. NMR data indicate that GRL0617 blocks the binding of ISG15 C-terminus to PLpro. Using truncated ISG15 mutants, we show that the C-terminus of ISG15 plays a dominant role in binding PLpro. Structural analysis reveals that the ISG15 C-terminus binding pocket in PLpro contributes a disproportionately large portion of binding energy, thus this pocket is a hot spot for antiviral drug discovery targeting PLpro.
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Cited by
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Metadata
- Authors
- Fu, Z., Huang, B., Tang, J., Liu, S., Liu, M., Ye, Y., Liu, Z., Xiong, Y., Zhu, W., Cao, D., Li, J., Niu, X., Zhou, H., Zhao, Y. J., Zhang, G., & Huang, H.
- Venue
- Nature Communications
- Published
- 2021-01-20
- Volume
- 12
- Issue
- 1
- Pages
- 488-488
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W3125094078
- Cited by
- 322
- References
- 62
- FWCI
- 19.18
- Type
- journal article
- Language
- en
- Open access
- gold
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- Fu, Z., Huang, B., Tang, J., Liu, S., Liu, M., Ye, Y., Liu, Z., Xiong, Y., Zhu, W., Cao, D., Li, J., Niu, X., Zhou, H., Zhao, Y. J., Zhang, G., & Huang, H. (2021). The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery. Nature Communications. https://doi.org/10.1038/s41467-020-20718-8
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