ArticleThe European respiratory journal2020
Cyclophilin inhibitors restrict Middle East respiratory syndrome coronavirus
Article in The European respiratory journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Broad-Spectrum Antiviral Activity of Cyclophilin Inhibitors Against Coronaviruses: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Cyclosporin A triggers a RIG-I-mediated interferon response through multiple cellular processes.Scientific reports · 2026Article
- Comparative genomics identifies small interfering RNA with activity against all five human betacoronaviruses.Genome medicine · 2026Article
- Attenuation of IFITM proteins' antiviral activity through sequestration into intraluminal vesicles of late endosomes.Frontiers in immunology · 2025Article
- AnHeliyon · 2024Article
- Cyclophilin inhibition as a strategy for the treatment of human disease.Frontiers in pharmacology · 2024Review
- Outcome of COVID-19 in Egyptian living-donor kidney transplant recipients and relation to maintenance immunosuppressive drugs: a pilot study.Scientific reports · 2023Article
- Non-Immunosuppressive Cyclophilin Inhibitors.Angewandte Chemie (International ed. in English) · 2022Review
- XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity.Journal of virology · 2022Article
- Repurposing of cyclophilin A inhibitors as broad-spectrum antiviral agents.Drug discovery today · 2022Review
- Proteomic landscape of SARS-CoV-2- and MERS-CoV-infected primary human renal epithelial cells.Life science alliance · 2022Article
- Cyclosporin A Reveals Potent Antiviral Effects in Preclinical Models of SARS-CoV-2 Infection.American journal of respiratory and critical care medicine · 2022Article
- The Cyclophilin-Dependent Calcineurin Inhibitor Voclosporin Inhibits SARS-CoV-2 Replication in Cell Culture.Transplant international : official journal of the European Society for Organ Transplantation · 2022Article
- Effects of immunophilin inhibitors and non-immunosuppressive analogs on coronavirus replication in human infection models.Frontiers in cellular and infection microbiology · 2022Article
- Emerging Roles of Cyclophilin A in Regulating Viral Cloaking.Frontiers in microbiology · 2022Review
- The Impact of SARS-CoV-2 Infection, and Application of Immunosuppressive Agents in Kidney Transplant Recipients Suffering from COVID-19.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Calcineurin-nuclear factor for activated T cells (NFAT) signaling in pathophysiology of wound healing.Inflammation and regeneration · 2021Review
- Intranasal Administration of a Monoclonal Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection.Viruses · 2021Article
- Cyclophilins and Their Roles in Hepatitis C Virus and Flavivirus Infections: Perspectives for Novel Antiviral Approaches.Pathogens (Basel, Switzerland) · 2021Review
- SARS-CoV-2 and mitochondrial health: implications of lifestyle and ageing.Immunity & ageing : I & A · 2020Review
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV), cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use.We elucidated the molecular mechanisms by which the cyclophilin inhibitors cyclosporin A (CsA) and alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily available therapy in MERS-CoV infection.Calu-3 cells and primary human alveolar epithelial cells (hAECs) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including calcineurin, nuclear factor of activated T-cells (NFATs) or mitogen-activated protein kinases. Novel CsA-induced pathways were identified by RNA sequencing and manipulated by gene knockdown or neutralising antibodies. Viral replication was quantified by quantitative real-time PCR and 50% tissue culture infective dose. Data were validated in a murine MERS-CoV infection model.Both CsA and ALV reduced MERS-CoV titres and viral RNA replication in Calu-3 cells and hAECs, improving epithelial integrity. While neither calcineurin nor NFAT inhibition reduced MERS-CoV propagation, blockade of c-Jun N-terminal kinase diminished infectious viral particle release but not RNA accumulation. Importantly, CsA induced interferon regulatory factor 1 (IRF1), a pronounced type III interferon (IFNλ) response and expression of antiviral genes. Downregulation of IRF1 or IFNλ increased MERS-CoV propagation in the presence of CsA. Importantly, oral application of CsA reduced MERS-CoV replication
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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.