Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jan;29(1):156-166.
doi: 10.1038/s41418-021-00844-6. Epub 2021 Aug 17.

Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 infection

Marcello Allegretti  1 , Maria Candida Cesta  2 , Mara Zippoli  2 , Andrea Beccari  2 , Carmine Talarico  2 , Flavio Mantelli  2 , Enrico M Bucci  3 , Laura Scorzolini  4 , Emanuele Nicastri  4
Affiliations
Review

Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 infection

Marcello Allegretti et al. Cell Death Differ. 2022 Jan.

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates strategies to identify prophylactic and therapeutic drug candidates to enter rapid clinical development. This is particularly true, given the uncertainty about the endurance of the immune memory induced by both previous infections or vaccines, and given the fact that the eradication of SARS-CoV-2 might be challenging to reach, given the attack rate of the virus, which would require unusually high protection by a vaccine. Here, we show how raloxifene, a selective estrogen receptor modulator with anti-inflammatory and antiviral properties, emerges as an attractive candidate entering clinical trials to test its efficacy in early-stage treatment COVID-19 patients.

PubMed Disclaimer

Conflict of interest statement

MA, MCC, MZ, AB, CT, and FM are permanent employees of Dompé Farmaceutici S.p.A, coordinator of the Horizon 2020 European project “N.101003551-EXSCALATE4CoV” and sponsor of the running clinical trial conducted with raloxifene on COVID-19 patients. EN and LS are employees of Lazzaro Spallanzani National Institute for Infectious Disease, IRCCS, Rome. EMB declares no conflict of interest.

Figures

Fig. 1
Fig. 1. SERM potential activities on COVID-19.
Effect of different SERM on organs, viruses and immune system. The up arrow means positive modulation; the down arrow negative modulation.
Fig. 2
Fig. 2
17β-estradiol derivatives and different SERM generations.
Fig. 3
Fig. 3. Structural analogies between SERMs and steroids.
A The ABCD steroid ring system in 17β-estradiol. B “A ring” and “D ring” marked in raloxifene.
Fig. 4
Fig. 4. Binding mode of raloxifene to ERα.
A 2D chemical structure of raloxifene and B three-dimensional schematic representation of raloxifene (RAL) complexed with the Estrogen Receptor (ER) Alpha Ligand Binding Domain (PDB Code: 7KBS). RAL and ER are reported in pink sticks and blue cartoon, respectively. The binding site region is shown in transparent surface.
Fig. 5
Fig. 5. In silico polypharmacological effects of raloxifene performed on the main SARS-CoV-2 proteins.
In supplementary information a predicted structure complex with raloxifene is reported for each SARS-CoV-2 protein.
See this image and copyright information in PMC

References

    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. - PMC - PubMed
    1. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–9. - PMC - PubMed
    1. European Centre for Disease Prevention and Control. Outbreak of novel coronavirus disease 2019 (COVID-19): increased transmission globally—fifth update, 2 March 2020. Stockholm: ECDC; 2020.
    1. Ruan YJ, Wei CL, Ee AL, Vega VB, Thoreau H, Su ST, et al. Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection. Lancet. 2003;361:1779–85. - PMC - PubMed
    1. Who Mers-Cov Research Group. State of Knowledge and Data Gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Humans. PLoS Curr. 2013;5:ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8. - PMC - PubMed

Publication types