ArticleCell death & disease2022
Characterization of raloxifene as a potential pharmacological agent against SARS-CoV-2 and its variants.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05172050 (Multicenter, Adaptive, Randomized, Placebo-controlled, Double Blind, Parallel-group Phase 2/3 Trial, to Study Efficacy and Safety of Two Doses of Raloxifene in Adult Paucisymptomatic COVID-19 Patients.), which is not on this map. Cited by 14 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Multicenter, Adaptive, Randomized, Placebo-controlled, Double Blind, Parallel-group Phase 2/3 Trial, to Study Efficacy and Safety of Two Doses of Raloxifene in Adult Paucisymptomatic COVID-19 Patients.
Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
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- Recent advances in drug repositioning and rediscovery for different therapeutic activities utilizing updated technological approaches.Molecular diversity · 2026Review
- Bazedoxifene and Beyond: Identifying This SERM's Targets and Deciphering Its Molecular Mechanisms.Advances in pharmacological and pharmaceutical sciences · 2026Review
- First real-world evidence from the Emilia-Romagna region suggests tamoxifen protects breast cancer patients from COVID-19.Scientific reports · 2025Article
- SARS-CoV-2 Entry Can Be Mimicked inViruses · 2025Article
- A Multi-Model Machine Learning Framework for Identifying Raloxifene as a Novel RNA Polymerase Inhibitor from FDA-Approved Drugs.Current issues in molecular biology · 2025Article
- Review
- Clinical outcomes of COVID-19 infection in patients with osteoporosis: a nationwide cohort study in Korea using the common data model.Scientific reports · 2024Article
- Learning from COVID-19: How drug hunters can prepare for the next pandemic.Drug discovery today · 2023Article
- Discovery of PLACS omega · 2023Article
- Relevance of Spike/Estrogen Receptor-α interaction for endothelial-based coagulopathy induced by SARS-CoV-2.Signal transduction and targeted therapy · 2023Article
- DHFR Inhibitors Display a Pleiotropic Anti-Viral Activity against SARS-CoV-2: Insights into the Mechanisms of Action.Viruses · 2023Article
- A phase 2 randomized, double-blinded, placebo-controlled, multicenter trial evaluating the efficacy and safety of raloxifene for patients with mild to moderate COVID-19.EClinicalMedicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The new coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic, which so far has caused over 6 million deaths in 2 years, despite new vaccines and antiviral medications. Drug repurposing, an approach for the potential application of existing pharmaceutical products to new therapeutic indications, could be an effective strategy to obtain quick answers to medical emergencies. Following a virtual screening campaign on the most relevant viral proteins, we identified the drug raloxifene, a known Selective Estrogen Receptor Modulator (SERM), as a new potential agent to treat mild-to-moderate COVID-19 patients. In this paper we report a comprehensive pharmacological characterization of raloxifene in relevant in vitro models of COVID-19, specifically in Vero E6 and Calu-3 cell lines infected with SARS-CoV-2. A large panel of the most common SARS-CoV-2 variants isolated in Europe, United Kingdom, Brazil, South Africa and India was tested to demonstrate the drug's ability in contrasting the viral cytopathic effect (CPE). Literature data support a beneficial effect by raloxifene against the viral infection due to its ability to interact with viral proteins and activate protective estrogen receptor-mediated mechanisms in the host cells. Mechanistic studies here reported confirm the significant affinity of raloxifene for the Spike protein, as predicted by in silico studies, and show that the drug treatment does not directly affect Spike/ACE2 interaction or viral internalization in infected cell lines. Interestingly, raloxifene can counteract Spike-mediated ADAM17 activation in human pulmonary cells, thus providing new insights on its mechanism of action. A clinical study in mild to moderate COVID-19 patients (NCT05172050) has been recently completed. Our contribution to evaluate raloxifene results on SARS-CoV-2 variants, and the interpretation of the mechanisms of action will be key elements to better understand the trial results, and to design new clinical studies aiming to evaluate the potential development of raloxifene in this indication.
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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 Socratic graph.