{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:22:58Z","timestamp":1793064178189,"version":"4.5.0"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Government","award":["RAPID 01Kl1723C\/01KI2006C"],"award-info":[{"award-number":["RAPID 01Kl1723C\/01KI2006C"]}]},{"name":"German Government","award":["TTU EI 01.806"],"award-info":[{"award-number":["TTU EI 01.806"]}]},{"name":"German Center for Infection Research","award":["RAPID 01Kl1723C\/01KI2006C"],"award-info":[{"award-number":["RAPID 01Kl1723C\/01KI2006C"]}]},{"name":"German Center for Infection Research","award":["TTU EI 01.806"],"award-info":[{"award-number":["TTU EI 01.806"]}]},{"name":"Merck KGaA, Darmstadt, Germany","award":["RAPID 01Kl1723C\/01KI2006C"],"award-info":[{"award-number":["RAPID 01Kl1723C\/01KI2006C"]}]},{"name":"Merck KGaA, Darmstadt, Germany","award":["TTU EI 01.806"],"award-info":[{"award-number":["TTU EI 01.806"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The emergence of human coronaviruses has led to three epidemics or pandemics in the last two decades, collectively causing millions of deaths and thus highlighting a long-term need to identify new antiviral drug targets and develop antiviral therapeutics. In this study, a compound library was screened to uncover novel potential inhibitors of coronavirus replication. Three lead compounds, designated #16-14, #16-23, and #16-24, which were Ixazomib and its analogs, were identified based on their potent antiviral activity and minimal cytotoxicity. These compounds were found to inhibit the immunoproteasome subunit LMP7, a target whose subcellular localization and expression are altered in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-infected Huh7 cells. Yeast two-hybrid assays and co-immunoprecipitation further revealed that LMP7 interacts with the viral proteins Nsp13 and Nsp16. In addition, Nsp13 and Nsp16 disrupted the expression of LMP7 in response to pathogen attacks. Functional studies showed that LMP7 knockout in BEAS-2B-ACE2 cells resulted in enhanced replication of attenuated SARS-CoV-2, highlighting the role of this subunit in restricting viral replication. Taken together, these findings position LMP7 as a novel therapeutic target and highlight Ixazomib and its analogs as potential antiviral agents against current and future coronavirus threats.<\/jats:p>","DOI":"10.3390\/pathogens14090871","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["LMP7 as a Target for Coronavirus Therapy: Inhibition by Ixazomib and Interaction with SARS-CoV-2 Proteins Nsp13 and Nsp16"],"prefix":"10.3390","volume":"14","author":[{"given":"Yi","family":"Ru","sequence":"first","affiliation":[{"name":"Max-von-Pettenkofer Institute, Virology Department, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Site, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5448-3509","authenticated-orcid":false,"given":"Yue","family":"Ma-Lauer","sequence":"additional","affiliation":[{"name":"Max-von-Pettenkofer Institute, Virology Department, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Site, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyu","family":"Xiang","sequence":"additional","affiliation":[{"name":"Max-von-Pettenkofer Institute, Virology Department, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Site, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Max-von-Pettenkofer Institute, Virology Department, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Site, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"von Brunn","sequence":"additional","affiliation":[{"name":"Max-von-Pettenkofer Institute, Virology Department, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Site, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Richter","sequence":"additional","affiliation":[{"name":"Institute of Virology, Campus Charite\u2019 Mitte, Charite\u2019-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Drosten","sequence":"additional","affiliation":[{"name":"Institute of Virology, Campus Charite\u2019 Mitte, Charite\u2019-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0166-1367","authenticated-orcid":false,"given":"Andreas","family":"Pichlmair","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7489-6557","authenticated-orcid":false,"given":"Susanne","family":"Pfefferle","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Klein","sequence":"additional","affiliation":[{"name":"Merck KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7611-7534","authenticated-orcid":false,"given":"Robert D.","family":"Damoiseaux","sequence":"additional","affiliation":[{"name":"Molecular Screening Shared Resource, California NanoSystems Institute (CNSI), The University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2355-7974","authenticated-orcid":false,"given":"Ulrich A. 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