Structural and functional insights into Ubl domain-mediated regulation of SARS-CoV-2 PLpro
Rimanshee Arya, Janani Ganesh, Vishal Prashar, Mukesh Kumar
Biology Direct, doi:10.1186/s13062-025-00690-3
domain that hydrolyzes peptide and isopeptide bonds of viral and cellular substrates. PLpro cleaves viral polyproteins to release Nsp1, Nsp2, and Nsp3 which is essential for viral replication [1, 2]. In addition, PLpro removes ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15) from the cellular protein substrates-a process known as deubiquitination (DUB) and deISGylation, respectively [2-4]. By acting as both a deubiquitinase and a deISGylase, PLpro enables SARS-CoV-2 to evade host immune responses. It impairs the interferon signalling pathway by removing Ub and ISG15 from key signalling proteins, thereby disrupting innate immunity [5-7]. Furthermore, PLpro-mediated deISGylation of the viral nucleocapsid protein enhances viral replication [8].
Supplementary Information The online version contains supplementary material available at h t t p s : / / d o i . o r g / 1 0 . 1 1 8 6 / s 1 3 0 6 2 -0 2 5 -0 0 6 9 0 -3.
Supplementary Material 1. Author contributions R.A.: Planned and performed experiments, analyzed data and written the manuscript, J.G.: Performed experiments, analyzed data and written the manuscript, V.P.: Supervised the research work, analyzed data and written the manuscript, M.K.: Supervised the research work, analyzed data and written the manuscript.
Declarations
Competing interests The authors declare no competing interests.
Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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