Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity.

Donghyuk ShinIvan Dikic


The papain-like protease PLpro is an essential coronavirus enzyme that is required for processing viral polyproteins to generate a functional replicase complex and enable viral spread1,2. PLpro is also implicated in cleaving proteinaceous post-translational modifications on host proteins as an evasion mechanism against host antiviral immune responses3-5. Here we perform biochemical, structural and functional characterization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PLpro (SCoV2-PLpro) and outline differences with SARS-CoV PLpro (SCoV-PLpro) in regulation of host interferon and NF-κB pathways. SCoV2-PLpro and SCoV-PLpro share 83% sequence identity but exhibit different host substrate preferences; SCoV2-PLpro preferentially cleaves the ubiquitin-like interferon-stimulated gene 15 protein (ISG15), whereas SCoV-PLpro predominantly targets ubiquitin chains. The crystal structure of SCoV2-PLpro in complex with ISG15 reveals distinctive interactions with the amino-terminal ubiquitin-like domain of ISG15, highlighting the high affinity and specificity of these interactions. Furthermore, upon infection, SCoV2-PLpro contributes to the cleavage of ISG15 from interferon responsive factor 3 (IRF3) and attenuates t...Continue Reading


Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Feb 22, 2005·BMC Molecular Biology·Xiaozhu ZhangAndrew J Sandford
Mar 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michel OuelletMichel J Tremblay
Sep 19, 2006·Immunity·Daniel B Stetson, Ruslan Medzhitov
Oct 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kiira RatiaAndrew D Mesecar
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jun 12, 2009·The Journal of Physical Chemistry. B·Robert B Best, Gerhard Hummer
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Mar 24, 2010·Molecular and Cellular Biology·He-Xin ShiChen Wang
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 22, 2010·Proteins·Kresten Lindorff-LarsenDavid E Shaw
Mar 30, 2012·Biophysical Journal·Robert B BestJeetain Mittal
Apr 17, 2012·Acta Crystallographica. Section D, Biological Crystallography·Pavel V AfoninePaul D Adams
Sep 11, 2012·Cell Reports·Radoslav I EnchevEdward P Morris
Dec 20, 2012·ELife·Brian J FergusonGeoffrey L Smith
Feb 8, 2013·Journal of the American Chemical Society·Reggy EkkebusHuib Ovaa
Mar 29, 2013·Bioorganic & Medicinal Chemistry·Stefanie SommerHenning D Mootz
Apr 15, 2014·Nature Biotechnology·Juan A VizcaínoHenning Hermjakob
Jul 16, 2014·Journal of Leukocyte Biology·Faruk SheikhRaymond P Donnelly
Mar 13, 2015·The Journal of Physical Chemistry. B·Stefano PianaDavid E Shaw
Nov 4, 2015·Nucleic Acids Research·Juan Antonio VizcaínoHenning Hermjakob
Jun 28, 2016·Nature Methods·Stefka TyanovaJürgen Cox
Feb 7, 2017·Nature Structural & Molecular Biology·Anja BastersGünter Fritz
Nov 22, 2017·Signal Transduction and Targeted Therapy·Ting LiuShao-Cong Sun
Mar 10, 2019·Methods in Enzymology·Paul P GeurinkHuib Ovaa
Nov 26, 2019·Antiviral Research·Jozlyn R ClasmanAndrew D Mesecar

❮ Previous
Next ❯


Aug 28, 2020·The EMBO Journal·Theresa KlemmDavid Komander
Oct 2, 2020·Pharmaceuticals·Anastasiia I Petushkova, Andrey A Zamyatnin
Oct 8, 2020·Signal Transduction and Targeted Therapy·Christopher B McClain, Nicolas Vabret
Oct 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lisa MiorinAdolfo García-Sastre
Oct 29, 2020·International Reviews of Immunology·Ashutosh KumarKamla Kant
Nov 29, 2020·Expert Opinion on Therapeutic Patents·Clemente CapassoClaudiu T Supuran
Nov 28, 2020·Postgraduate Medicine·Sairaj SatarkerMadhavan Nampoothiri
Dec 18, 2020·Emerging Microbes & Infections·Mengxia LiGuiqing Peng
Dec 19, 2020·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Hongjie Xia, Pei-Yong Shi
Jan 1, 2021·Journal of Structural Biology·Munazza Shahid, Syed Shahzad-Ul-Hussan
Nov 28, 2020·Journal of Molecular Biology·Rimanshee AryaMukesh Kumar
Jan 14, 2021·The Biochemical Journal·George M Burslem
Oct 25, 2020·The Protein Journal·Mihaela Ileana Ionescu
Dec 8, 2020·Heliyon·José Avendaño-OrtizEduardo López-Collazo
Jan 21, 2021·Experimental Biology and Medicine·Suresh MishraBl Grégoire Nyomba
Jan 26, 2021·Journal, Genetic Engineering & Biotechnology·Haruna Isiyaku UmarProsper Obed Chukwuemeka
Jan 31, 2021·Applied Microbiology and Biotechnology·Amin GasmiGeir Bjørklund
Feb 5, 2021·Journal of Chemical Information and Modeling·Anjela ManandharKhaled M Elokely
Oct 6, 2020·IScience·Johannes BurtscherGrégoire P Millet
Jan 22, 2021·Journal of Medical Virology·Varada AnirudhanLijun Rong
Jan 18, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Lina Herhaus
Dec 22, 2020·Expert Opinion on Drug Discovery·Carolina L BelleraAlan Talevi
Jan 13, 2021·Cell Death and Differentiation·Peter E CockramDomagoj Vucic
Feb 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ziyad Tariq MuhseenGuanglin Li
Feb 4, 2021·Nature Communications·Jerzy OsipiukAndrzej Joachimiak
Feb 10, 2021·Infectious Disease Reports·Andrew R McGillShyam S Mohapatra
Oct 27, 2020·Frontiers in Cell and Developmental Biology·Dina H Kassem, Mohamed M Kamal
Dec 16, 2020·Cellular & Molecular Immunology·Alejandra Gomez-CadenaCamilla Jandus
Jan 7, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Bhavesh D KevadiyaHoward E Gendelman
Jan 21, 2021·Biomolecules·Gonca ÇetinFrédéric Ebstein
Feb 9, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Dengke TianWenqiang Cao
Jan 6, 2021·International Journal of Molecular Sciences·Ramesh KumarSujatha Sunil
Feb 8, 2021·Stem Cell Research·Gangyu SunZhizhi Wang
Nov 19, 2020·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Madeleine Ennis, Katerina Tiligada
Dec 6, 2020·Biochemical and Biophysical Research Communications·Daoqun LiLeiliang Zhang
Feb 28, 2021·Cellular & Molecular Immunology·Wenjing WangJianwei Wang

❮ Previous
Next ❯

Methods Mentioned

nuclear translocation
size exclusion chromatography
size-exclusion chromatography

Software Mentioned

Sequest HT

Related Concepts

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.


Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.


Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.