Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Apr 6;13(12):940–953. doi: 10.1007/s13238-022-00909-3

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Interaction between F0213 and SARS2-PLpro or MERS-PLpro. (A) Docking F0213 to SARS2-PLpro. Left, molecular surface of SARS2-PLpro (colored cyan) with GRL0617 (colored gold, PDB: 7JRN) and F0213 (colored magenta, docking model) shown in stick model. The substrate binding cleft and the BL2 loop near active site is indicated. Middle, ribbon model of SARS2-PLpro with bound mouse ISG15 (colored yellow, PDB: 6YVA). The C-terminus of mISG15 is shown with the stick model. The predicted binding mode of F0213 (magenta) is shown with stick model. Right, detailed interaction between F0213 and SARS2-PLpro; residues were predicted to interact with the inhibitor are shown with the stick models (blue). (B) In vitro inhibition of WT and mutant SARS2-PLpro by F0213. Fixed concentration of PLpro (0.1 µmol/L) and 5 µmol/L of RLRGG-AMC substrate were incubated with serial-diluted F0213. Two-way ANOVA when compared with the WT % inhibition of in each F0213 concentration. (C) Isothermal titration calorimetry (ITC) experiments for the binding between SARS2-PLpro and inhibitors as indicated. Disassociation constant K_D is indicated; N.D. stands for non-detectable. (D) Docking F0213 to MERS- PLpro. Left, ribbon model of MERS-PLpro (colored light blue) bound by human ISG15 (colored yellow, PDB: 6BI8) is overlaid with the predicted binding mode of F0213 (colored magenta). The BL2 loop is indicated. Right, detailed interaction between F0213 and MERS-CoV PLpro; residues that were predicted to interact with the inhibitor are shown with the stick models and colored blue. (E) In vitro inhibition of WT and mutant MERS-PLpro by F0213. Two-way ANOVA when compared with the WT % inhibition of in each F0213 concentration. (F) ITC experiments for the binding between MERS-PLpro (WT or mutant) and inhibitors as indicated. Disassociation constant K_D is indicated; N.D. stands for non-detectable. (G) Recombinant virus carrying the E271A substitution in MERS-CoV NSP3 confers resistance to F0213. VeroE6 cells were infected with wild-type or mutant MERS-CoV generated by reverse genetics. Antiviral activities were determined by plaque assay detecting the live virus particle in the supernatant. Results are shown as the ratio between F0123-treated and vehicle treated groups that were infected by the same virus. Two-way ANOVA. For all statistical analysis, ****P < 0.0001, ***P < 0.001, **P < 0.01,*P < 0.05