ArticleBiochemical pharmacology2020
AR12 (OSU-03012) suppresses GRP78 expression and inhibits SARS-CoV-2 replication.
Article in Biochemical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- GRP78 in human diseases: From molecular chaperone to therapeutic target.Theranostics · 2026Review
- A Heparan Sulfate Mimetic RAFT Copolymer Inhibits SARS-CoV-2 Infection and Ameliorates Viral-Induced Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance.Viruses · 2025Article
- Nature's cryptographic codebreakerFrontiers in microbiology · 2025Article
- Autophagy-enhancing strategies to promote intestinal viral resistance and mucosal barrier function in SARS-CoV-2 infection.Autophagy reports · 2025Article
- Coronavirus M protein promotes mitophagy over virophagy by recruiting PDPK1 to phosphorylate SQSTM1 at T138.Nature communications · 2024Article
- Targeting stress induction of GRP78 by cardiac glycoside oleandrin dually suppresses cancer and COVID-19.Cell & bioscience · 2024Article
- Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma.medRxiv : the preprint server for health sciences · 2024Article
- Protein Quality Control Systems and ER Stress as Key Players in SARS-CoV-2-Induced Neurodegeneration.Cells · 2024Review
- SARS-CoV-2 nonstructural protein 6 triggers endoplasmic reticulum stress-induced autophagy to degrade STING1.Autophagy · 2023Article
- COVID-19, Obesity, and GRP78: Unraveling the Pathological Link.Journal of obesity & metabolic syndrome · 2023Review
- Review
- COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- GRP78 Inhibitor YUM70 Suppresses SARS-CoV-2 Viral Entry, Spike Protein Production and Ameliorates Lung Damage.Viruses · 2023Article
- Therapeutic potential of green tea catechin, (-)-epigallocatechin-3-Phytomedicine plus : international journal of phytotherapy and phytopharmacology · 2023Review
- Reply to: The stress-inducible ER chaperone GRP78/BiP is upregulated during SARS-CoV-2 infection and acts as a pro-viral protein.Nature communications · 2022Article
- The stress-inducible ER chaperone GRP78/BiP is upregulated during SARS-CoV-2 infection and acts as a pro-viral protein.Nature communications · 2022Article
- Article
- Review
- GRP78, a Novel Host Factor for SARS-CoV-2: The Emerging Roles in COVID-19 Related to Metabolic Risk Factors.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AR12 is a derivative of celecoxib which no-longer acts against COX2 but instead inhibits the ATPase activity of multiple chaperone proteins, in particular GRP78. GRP78 acts as a sensor of endoplasmic reticulum stress and is an essential chaperone required for the life cycle of all mammalian viruses. We and others previously demonstrated in vitro and in vivo that AR12 increases autophagosome formation and autophagic flux, enhances virus protein degradation, preventing virus reproduction, and prolonging the survival of infected animals. In this report, we determined whether AR12 could act against SARS-CoV-2. In a dose-dependent fashion AR12 inhibited SARS-CoV-2 spike protein expression in transfected or infected cells. AR12 suppressed the production of infectious virions via autophagosome formation, which was also associated with degradation of GRP78. After AR12 exposure, the colocalization of GRP78 with spike protein was reduced. Knock down of eIF2α prevented AR12-induced spike degradation and knock down of Beclin1 or ATG5 caused the spike protein to localize in LAMP2+ vesicles without apparent degradation. HCT116 cells expressing ATG16L1 T300, found in the majority of persons of non-European descent, particularly from Africa, expressed greater amounts of GRP78 and SARS-CoV-2 receptor angiotensin converting enzyme 2 compared to ATG16L1 A300, predominantly found in Europeans, suggestive that ATG16L1 T300 expression may be associated with a greater ability to be infected and to reproduce SARS-CoV-2. In conclusion, our findings demonstrate that AR12 represents a clinically relevant anti-viral drug for the treatment of SARS-CoV-2.
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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.