ArticleJournal of virology2012
Severe acute respiratory syndrome coronavirus replication is severely impaired by MG132 due to proteasome-independent inhibition of M-calpain.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
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Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Inhibition of calpain-mediated BAX cleavage attenuates Japanese encephalitis virus-induced apoptosis in SH-SY5Y neuroblastoma cells.Virology journal · 2026Article
- Mitochondrial OXPHOS restricts SARS-CoV-2 replication.Science advances · 2026Article
- Broad-acting antivirals: the pursuit of pan-viral therapeutics in the era of pandemics.Journal of virology · 2026Review
- Andrographolide targets syndecan4 to impair its interaction with syntenin and inhibits the biogenesis of small extracellular vesicles.The Journal of biological chemistry · 2026Article
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- In depth sequencing of a serially sampled household cohort reveals the within-host dynamics of Omicron SARS-CoV-2 and rare selection of novel spike variants.PLoS pathogens · 2025Article
- Immune pressure is key to understanding observed patterns of respiratory virus evolution in prolonged infections.Virus evolution · 2025Article
- Effects of immunoproteasome inhibition on acute respiratory infection with murine hepatitis virus strain 1.Journal of virology · 2024Article
- Taming the storm: potential anti-inflammatory compounds targeting SARS-CoV-2 MPro.Inflammopharmacology · 2024Review
- Structural Elucidation and Antiviral Activity of Covalent Cathepsin L Inhibitors.Journal of medicinal chemistry · 2024Article
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- Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1.Signal transduction and targeted therapy · 2024Article
- Natural Compounds as Protease Inhibitors in Therapeutic Focus on Cancer Therapy.Anti-cancer agents in medicinal chemistry · 2024Review
- Mechanism, structural and functional insights into nidovirus-induced double-membrane vesicles.Frontiers in immunology · 2024Review
- The social role of defective viral genomes in chronic viral infections: a commentary on Leeks et al. 2023.Journal of evolutionary biology · 2023Article
- The Local Anaesthetic Procaine Prodrugs ProcClusterInternational journal of molecular sciences · 2023Article
- The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry.Viruses · 2023Article
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- Subversion of autophagy machinery and organelle-specific autophagy by SARS-CoV-2 and coronaviruses.Autophagy · 2023Review
51 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitin-proteasome system (UPS) is involved in the replication of a broad range of viruses. Since replication of the murine hepatitis virus (MHV) is impaired upon proteasomal inhibition, the relevance of the UPS for the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) was investigated in this study. We demonstrate that the proteasomal inhibitor MG132 strongly inhibits SARS-CoV replication by interfering with early steps of the viral life cycle. Surprisingly, other proteasomal inhibitors (e.g., lactacystin and bortezomib) only marginally affected viral replication, indicating that the effect of MG132 is independent of proteasomal impairment. Induction of autophagy by MG132 treatment was excluded from playing a role, and no changes in SARS-CoV titers were observed during infection of wild-type or autophagy-deficient ATG5(-/-) mouse embryonic fibroblasts overexpressing the human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2). Since MG132 also inhibits the cysteine protease m-calpain, we addressed the role of calpains in the early SARS-CoV life cycle using calpain inhibitors III (MDL28170) and VI (SJA6017). In fact, m-calpain inhibition with MDL28170 resulted in an even more pronounced inhibition of SARS-CoV replication (>7 orders of magnitude) than did MG132. Additional m-calpain knockdown experiments confirmed the dependence of SARS-CoV replication on the activity of the cysteine protease m-calpain. Taken together, we provide strong experimental evidence that SARS-CoV has unique replication requirements which are independent of functional UPS or autophagy pathways compared to other coronaviruses. Additionally, this work highlights an important role for m-calpain during early steps of the SARS-CoV life cycle.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.