Potent and selective inhibition of pathogenic viruses by engineered ubiquitin variants.
Identifieur interne : 000C83 ( PubMed/Corpus ); précédent : 000C82; suivant : 000C84Potent and selective inhibition of pathogenic viruses by engineered ubiquitin variants.
Auteurs : Wei Zhang ; Ben A. Bailey-Elkin ; Robert C M. Knaap ; Baldeep Khare ; Tim J. Dalebout ; Garrett G. Johnson ; Puck B. Van Kasteren ; Nigel J. Mcleish ; Jun Gu ; Wenguang He ; Marjolein Kikkert ; Brian L. Mark ; Sachdev S. SidhuSource :
- PLoS pathogens [ 1553-7374 ] ; 2017.
English descriptors
- KwdEn :
- Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Coronavirus Infections (metabolism), Coronavirus Infections (virology), Drug Evaluation, Preclinical, Enzyme Inhibitors (chemistry), Enzyme Inhibitors (pharmacology), Hemorrhagic Fever Virus, Crimean-Congo (drug effects), Hemorrhagic Fever Virus, Crimean-Congo (enzymology), Hemorrhagic Fever Virus, Crimean-Congo (genetics), Hemorrhagic Fever, Crimean (metabolism), Hemorrhagic Fever, Crimean (virology), Humans, Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (enzymology), Middle East Respiratory Syndrome Coronavirus (genetics), Ubiquitin (metabolism), Ubiquitination (drug effects), Viral Proteins (antagonists & inhibitors), Viral Proteins (chemistry), Viral Proteins (genetics), Viral Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemistry : Antiviral Agents, Enzyme Inhibitors, Viral Proteins.
- chemical , genetics : Viral Proteins.
- chemical , metabolism : Ubiquitin, Viral Proteins.
- chemical , pharmacology : Antiviral Agents, Enzyme Inhibitors.
- drug effects : Hemorrhagic Fever Virus, Crimean-Congo, Middle East Respiratory Syndrome Coronavirus, Ubiquitination.
- enzymology : Hemorrhagic Fever Virus, Crimean-Congo, Middle East Respiratory Syndrome Coronavirus.
- genetics : Hemorrhagic Fever Virus, Crimean-Congo, Middle East Respiratory Syndrome Coronavirus.
- metabolism : Coronavirus Infections, Hemorrhagic Fever, Crimean.
- virology : Coronavirus Infections, Hemorrhagic Fever, Crimean.
- Drug Evaluation, Preclinical, Humans.
Abstract
The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses. A variety of viral DUBs (vDUBs), including the MERS-CoV papain-like protease, are responsible for cleaving the viral replicase polyproteins during replication, and are thereby critical components of the viral replication cycle. Together, this makes vDUBs highly attractive antiviral drug targets. However, structural similarity between the catalytic cores of vDUBs and human DUBs complicates the development of selective small molecule vDUB inhibitors. We have thus developed an alternative strategy to target the vDUB activity through a rational protein design approach. Here, we report the use of phage-displayed ubiquitin variant (UbV) libraries to rapidly identify potent and highly selective protein-based inhibitors targeting the DUB domains of MERS-CoV and CCHFV. UbVs bound the vDUBs with high affinity and specificity to inhibit deubiquitination, deISGylation and in the case of MERS-CoV also viral replicative polyprotein processing. Co-crystallization studies further revealed critical molecular interactions between UbVs and MERS-CoV or CCHFV vDUBs, accounting for the observed binding specificity and high affinity. Finally, expression of UbVs during MERS-CoV infection reduced infectious progeny titers by more than four orders of magnitude, demonstrating the remarkable potency of UbVs as antiviral agents. Our results thereby establish a strategy to produce protein-based inhibitors that could protect against a diverse range of viruses by providing UbVs via mRNA or protein delivery technologies or through transgenic techniques.
DOI: 10.1371/journal.ppat.1006372
PubMed: 28542609
Links to Exploration step
pubmed:28542609Le document en format XML
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<front><div type="abstract" xml:lang="en">The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses. A variety of viral DUBs (vDUBs), including the MERS-CoV papain-like protease, are responsible for cleaving the viral replicase polyproteins during replication, and are thereby critical components of the viral replication cycle. Together, this makes vDUBs highly attractive antiviral drug targets. However, structural similarity between the catalytic cores of vDUBs and human DUBs complicates the development of selective small molecule vDUB inhibitors. We have thus developed an alternative strategy to target the vDUB activity through a rational protein design approach. Here, we report the use of phage-displayed ubiquitin variant (UbV) libraries to rapidly identify potent and highly selective protein-based inhibitors targeting the DUB domains of MERS-CoV and CCHFV. UbVs bound the vDUBs with high affinity and specificity to inhibit deubiquitination, deISGylation and in the case of MERS-CoV also viral replicative polyprotein processing. Co-crystallization studies further revealed critical molecular interactions between UbVs and MERS-CoV or CCHFV vDUBs, accounting for the observed binding specificity and high affinity. Finally, expression of UbVs during MERS-CoV infection reduced infectious progeny titers by more than four orders of magnitude, demonstrating the remarkable potency of UbVs as antiviral agents. Our results thereby establish a strategy to produce protein-based inhibitors that could protect against a diverse range of viruses by providing UbVs via mRNA or protein delivery technologies or through transgenic techniques.</div>
</front>
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<Abstract><AbstractText>The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses. A variety of viral DUBs (vDUBs), including the MERS-CoV papain-like protease, are responsible for cleaving the viral replicase polyproteins during replication, and are thereby critical components of the viral replication cycle. Together, this makes vDUBs highly attractive antiviral drug targets. However, structural similarity between the catalytic cores of vDUBs and human DUBs complicates the development of selective small molecule vDUB inhibitors. We have thus developed an alternative strategy to target the vDUB activity through a rational protein design approach. Here, we report the use of phage-displayed ubiquitin variant (UbV) libraries to rapidly identify potent and highly selective protein-based inhibitors targeting the DUB domains of MERS-CoV and CCHFV. UbVs bound the vDUBs with high affinity and specificity to inhibit deubiquitination, deISGylation and in the case of MERS-CoV also viral replicative polyprotein processing. Co-crystallization studies further revealed critical molecular interactions between UbVs and MERS-CoV or CCHFV vDUBs, accounting for the observed binding specificity and high affinity. Finally, expression of UbVs during MERS-CoV infection reduced infectious progeny titers by more than four orders of magnitude, demonstrating the remarkable potency of UbVs as antiviral agents. Our results thereby establish a strategy to produce protein-based inhibitors that could protect against a diverse range of viruses by providing UbVs via mRNA or protein delivery technologies or through transgenic techniques.</AbstractText>
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<ForeName>Sachdev S</ForeName>
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<ArticleIdList><ArticleId IdType="pubmed">28542609</ArticleId>
<ArticleId IdType="doi">10.1371/journal.ppat.1006372</ArticleId>
<ArticleId IdType="pii">PPATHOGENS-D-17-00149</ArticleId>
<ArticleId IdType="pmc">PMC5451084</ArticleId>
</ArticleIdList>
<ReferenceList><Reference><Citation>Nat Cell Biol. 2016 May 27;18(6):579-86</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27230526</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):E838-47</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23401522</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2005 Dec;79(24):15189-98</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16306590</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2007 Jun;81(11):6007-18</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17392370</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>ACS Chem Biol. 2016 Apr 15;11(4):1058-65</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26745345</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Ther. 2004 Feb;9(2):209-17</Citation>
<ArticleIdList><ArticleId IdType="pubmed">14759805</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Pharm. 2015 Aug 3;12(8):2962-71</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26103531</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Infect Dis. 2016 Mar 1;213(5):712-22</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26486634</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2014 Oct;88(20):11886-98</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25100843</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Virology. 2014 Feb;450-451:64-70</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24503068</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Microbiol. 2016 Nov 28;2:16226</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27892925</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Science. 2013 Feb 1;339(6119):590-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23287719</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Virus Res. 2014 Dec 19;194:184-90</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24512893</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2228-33</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21266548</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Chem Biol. 2014 Sep 18;21(9):1102-14</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25237857</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>ACS Chem Biol. 2014 Aug 15;9(8):1662-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24936957</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2013 Aug;9(8):e1003560</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23966860</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>FEBS J. 2014 Sep;281(18):4085-96</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25039866</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell Host Microbe. 2007 Dec 13;2(6):404-16</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18078692</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 2007 Nov 2;282(44):32208-21</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17761676</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):8705-10</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27436899</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Antiviral Res. 2014 Sep;109:72-82</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24992731</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell Host Microbe. 2009 Jun 18;5(6):559-70</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19527883</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2005 Dec;79(24):15199-208</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16306591</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Microbiol. 2016 Aug;14 (8):523-34</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27344959</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Antiviral Res. 2015 Oct;122:28-38</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26192750</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2007 Apr;63(Pt 4):550-4</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17372361</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Gen Virol. 2013 Jul;94(Pt 7):1554-67</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23596270</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2013 Nov;87(21):11851-60</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23986588</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Antiviral Res. 2015 Mar;115:21-38</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25554382</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>ACS Chem Biol. 2015 Jun 19;10 (6):1456-65</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25746232</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Gen Virol. 2014 Mar;95(Pt 3):614-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24362959</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Mol Biol. 2013 Dec 13;425(24):4995-5008</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24095857</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2010 Jan;84(1):216-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19864393</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Prog Med Chem. 2016;55:149-92</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26852935</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Protoc. 2007;2(6):1368-86</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17545975</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2222-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21245344</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Cell. 2016 Apr 7;62(1):121-36</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26949039</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Immunol. 2011 Dec 09;12(1):35-48</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22158412</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell. 2015 Apr 23;161(3):674-90</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25910214</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2007 Apr;81(8):3922-32</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17251282</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8738-43</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26124093</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):564-70</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17452781</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2015 Apr;89(7):3659-70</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25589660</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2011 Oct;85(20):10899-904</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21835791</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2017 Apr 11;114(15):E3119-E3128</Citation>
<ArticleIdList><ArticleId IdType="pubmed">28348219</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):572-81</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24531491</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Mol Biol. 2007 Sep 21;372(3):774-97</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17681537</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Science. 2016 Jan 1;351(6268):77-81</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26678878</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2010 May;84(9):4619-29</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20181693</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Biochem J. 2015 Jan 1;465(1):1-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25631680</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Annu Rev Biochem. 2012;81:203-29</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22524316</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>EMBO J. 2012 Feb 1;31(3):741-53</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22117220</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 2014 Dec 12;289(50):34667-82</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25320088</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4970-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24599590</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS One. 2012;7(3):e32857</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22412934</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2004 Mar;60(Pt 3):601-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">14993707</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5717-22</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16581910</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell Mol Life Sci. 2013 Mar;70(5):815-28</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22833168</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell Res. 2008 Nov;18(11):1105-13</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18957937</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cells. 2014 May 06;3(2):386-417</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24805990</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
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