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

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.

SUBMITTER: Allegretti M

PROVIDER: S-EPMC8370058 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Allegretti Marcello M Cesta Maria Candida MC Zippoli Mara M Beccari Andrea A Talarico Carmine C Mantelli Flavio F Bucci Enrico M EM Scorzolini Laura L Nicastri Emanuele E

Cell death and differentiation 20210817 1

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 rat ...[more]

PMID: 34404919

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Antileishmanial activity of the estrogen receptor modulator raloxifene.

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| S-EPMC4014391 | biostudies-literature

Repurposing the selective estrogen receptor modulator bazedoxifene to suppress gastrointestinal cancer growth.

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Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen-Deficient Rat.

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The selective estrogen receptor modulator raloxifene mitigates the effect of all-<i>trans</i>-retinal toxicity in photoreceptor degeneration.

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| S-EPMC6579480 | biostudies-literature

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| S-EPMC8001969 | biostudies-literature

Repurposing of a clinically used anti-HPV agent to prevent and treat SARS-CoV-2 infection as an intranasal formulation.

Project description: Not available

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Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor.

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| S-EPMC8646421 | biostudies-literature

Estrogen, SNP-Dependent Chemokine Expression and Selective Estrogen Receptor Modulator Regulation.

Project description:We previously reported, on the basis of a genome-wide association study for aromatase inhibitor-induced musculoskeletal symptoms, that single-nucleotide polymorphisms (SNPs) near the T-cell leukemia/lymphoma 1A (TCL1A) gene were associated with aromatase inhibitor-induced musculoskeletal pain and with estradiol (E2)-induced TCL1A expression. Furthermore, variation in TCL1A expression influenced the downstream expression of proinflammatory cytokines and cytokine receptors. Specifically, the top hit genome-wide association study SNP, rs11849538, created a functional estrogen response element (ERE) that displayed estrogen receptor (ER) binding and increased E2 induction of TCL1A expression only for the variant SNP genotype. In the present study, we pursued mechanisms underlying the E2-SNP-dependent regulation of TCL1A expression and, in parallel, our subsequent observations that SNPs at a distance from EREs can regulate ERα binding and that ER antagonists can reverse phenotypes associated with those SNPs. Specifically, we performed a series of functional genomic studies using a large panel of lymphoblastoid cell lines with dense genomic data that demonstrated that TCL1A SNPs at a distance from EREs can modulate ERα binding and expression of TCL1A as well as the expression of downstream immune mediators. Furthermore, 4-hydroxytamoxifen or fulvestrant could reverse these SNP-genotype effects. Similar results were found for SNPs in the IL17A cytokine and CCR6 chemokine receptor genes. These observations greatly expand our previous results and support the existence of a novel molecular mechanism that contributes to the complex interplay between estrogens and immune systems. They also raise the possibility of the pharmacological manipulation of the expression of proinflammatory cytokines and chemokines in a SNP genotype-dependent fashion.

| S-EPMC4771694 | biostudies-literature

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