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Clofazimine is a broad-spectrum coronavirus inhibitor that antagonizes SARS-CoV-2 replication in primary human cell culture and hamsters

ABSTRACT: Clofazimine is a broad-spectrum coronavirus inhibitor that antagonizes SARS-CoV-2 replication in primary human cell culture and hamsters

PROVIDER: PRJNA683662 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13221603_1.fastq.gz	Fastqsanger.gz
	SRR13221603_2.fastq.gz	Fastqsanger.gz
	SRR13221604_1.fastq.gz	Fastqsanger.gz
	SRR13221604_2.fastq.gz	Fastqsanger.gz
	SRR13221605_1.fastq.gz	Fastqsanger.gz

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Clofazimine is a broad-spectrum coronavirus inhibitor that antagonizes SARS-CoV-2 replication in primary human cell culture and hamsters

Project description:COVID-19 is the third outbreak of zoonotic coronavirus (CoV) of the century after the epidemic Severe acute respiratory syndrome CoV (SARS-CoV) in 2003 and Middle East respiratory syndrome CoV (MERS-CoV) in 2012. Treatment options for CoVs are largely lacking. Here, we show that clofazimine, an anti-leprosy drug with favorable safety and pharmacokinetics profile, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 replication in multiple in vitro systems, including the human embryonic stem cell-derived cardiomyocytes and ex vivo lung cultures. The FDA-approved molecule was found to inhibit multiple steps of viral replication, suggesting polypharmacology is likely underlying its antiviral activity. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic and therapeutic administration of clofazimine significantly reduced lung viral load and fecal viral shedding, as well as reversal of cytokine storm. Additionally, clofazimine exhibited antiviral drug synergy when administered with remdesivir. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. Taken together, our data provide evidence that clofazimine may prove effective against current pandemic SARS-CoV-2, endemic MERS-CoV in the Middle East, and, possibly most importantly, emerging CoV of the future.

2021-02-02 | GSE162899 | GEO

Clofazimine is a broad-spectrum coronavirus inhibitor that antagonizes SARS-CoV-2 replication in primary human cell culture and hamsters.

Project description: Not available

| S-EPMC7553155 | biostudies-literature

An mRNA-based broad-spectrum antiviral inspired by ISG15 deficiency protects against viral infections in vitro and in vivo

Project description:Type I interferons (IFN-I) are cytokines with potent antiviral and inflammatory capacities. IFN-I signaling drives the expression of thousands of IFN-I stimulated genes (ISGs), whose aggregate function results in the control of viral infections. A few of these ISGs are tasked with negatively regulating the IFN-I response to prevent overt inflammation. ISG15 is a negative regulator whose absence leads to persistent, low-grade elevation of ISG expression and concurrent, often self-resolving, mild autoinflammation. The limited breadth and low-grade persistence of ISGs expressed in ISG15 deficiency are sufficient to confer broad-spectrum antiviral resistance. Inspired by the antiviral state of humans with ISG15 deficiency, we identified a nominal collection of 10 ISGs that recapitulated the broad antiviral potential of the IFN-I system, which typically induces the expression of thousands of ISGs. The expression of this 10-ISG collection in an IFN-I non-responsive cell line increased cellular resistance to Zika virus, vesicular stomatitis virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A lipid nanoparticle-encapsulated mRNA formulation of this 10-ISG collection significantly reduced IAV plaque size in vivo in mice when given prophylactically. Moreover, when used collectively and delivered prophylactically, 10-ISG was able to protect hamsters against a lethal SARS-CoV-2 challenge, in contrast with the lack of efficacy when mRNAs were delivered individually. These findings suggest that these 10 ISGs have potential as a broad-spectrum antiviral prophylactic.

2025-08-13 | GSE301682 | GEO

An mRNA-based broad-spectrum antiviral inspired by ISG15 deficiency protects against viral infections in vitro and in vivo II

2025-08-13 | GSE301683 | GEO

Evaluation of clofazimine treatment on functional gene transcription in hepatocellular carcinoma cells

Project description:Clofazimine (CFZ) is an orally administered anti-mycobacterial drug that demonstrates a broad spectrum of activity against mycobacterial infections, including leprosy and tuberculosis. CFZ also possesses anti-inflammatory and anti-tumor properties by disrupting DNA replication and inhibiting the production of IL2. Currently, this compound has been utilized in research related to drug-resistant cancer treatment, and has gained increasing recognition for its potential to enhance cancer treatment in recent years. Considering the benefits of CFZ in clinical settings, it presents itself as a promising candidate for combination drug therapy aimed at hepatocellular carcinoma through the regulation of functional gene transcription. Herein, we primarily examine the role of CFZ treatment throughout the functional gene transcription process in hepatocellular carcinoma cells.

2026-04-15 | GSE327600 | GEO

Broad-spectrum antibiotics disrupt homeostatic efferocytosis

Project description:Broad-spectrum antibiotics disrupt homeostatic efferocytosis

| PRJNA1128117 | ENA

Clofazimine derivatives as potent broad-spectrum antiviral agents with dual-target mechanism.

Project description: Not available

| S-EPMC8897968 | biostudies-literature

Clofazimine induced changes in the host immune system

Project description:Clofazimine (CLO), an antibiotic drug has been in use as such for more than 50 years to treat Mycobacterium leprosae and MDR Mycobacterium tuberculosis infections in humans. Long suspected and proven during the COVID pandemic the drug also has a secondary function as a modulator of the host immune system. We want to measure changes in the transcriptome of cells (bulk RNAseq) treated with CLO at t=6h where we see the onset of phenotypic changes in these cells without the typical cell death induced at higher CLO concentrations over a longer period of time.

2026-04-22 | GSE294972 | GEO

Targeting the SREBP-dependent lipidomic reprogramming by virus infection for broad-spectrum therapeutic intervention

Project description:Viruses are obligate intracellular parasites that exploit the host metabolic machineries to meet their extraordinary biosynthetic demands. Integrative transcriptomic and lipidomic profiling confirmed that Middle East respiratory syndrome coronavirus (MERS-CoV) infection reprograms the host lipid metabolism. By exploring a bioactive lipid library, we identified a tool compound, AM580 which is highly potent in interrupting the life cycle of diverse viruses including MERS-CoV and influenza A virus.</br> Using click chemistry, the sterol regulatory element binding protein (SREBP) was identified as the primary cellular target of AM580 which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as an ideal target for the development of broad-spectrum intervention strategies.

2018-11-26 | MTBLS762 | MetaboLights

Brd2 inhibitor ABBV-744 inhibits SARS-CoV-2 infection in Syrian Hamsters

Project description:We tested if Brd2 inhibitor ABBV-744 could reduce SARS-CoV-2 infection in Syrian Hamsters. Three days post-infection, the lungs of hamsters were harvested and subjected to RNA-seq. Infected, but untreated, hamsters showed marked up-regulation of a number of genes including ISGs when compared to uninfected controls. In contrast, hamsters treated with ABBV-744 showed a down-regulation of ISG levels, confirming ABBV-744 activity. Thus, Brd2 inhibition can decrease SARS-CoV-2 infection in Syrian Hamsters.

2021-09-02 | GSE182994 | GEO

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