ArticleUnited European gastroenterology journal2023
Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir.
Article in United European gastroenterology journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Organoids in respiratory virus research: advances and perspectives.Molecular biomedicine · 2025Review
- Mycophenolate mofetil exerts broad-spectrum antiviral activity against coronaviruses including SARS-CoV-2.Virology journal · 2025Article
- Refractory pneumonia due to persistent SARS-CoV-2 infection in an immunocompromised host successfully treated with extended course nirmatrelvir/ritonavir.ASM case reports · 2025Article
- Identification of C/EBPδ-Modifying Compounds as Potential Anticancer Agents Using a High-Throughput Drug Screen.Journal of cellular and molecular medicine · 2025Article
- SARS-CoV-2 and immunosuppressors at cellular level: Some good news.United European gastroenterology journal · 2023Article
- Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir.United European gastroenterology journal · 2023Article
- COVID-19 infection characteristics, risk factors and its potential impacts on Takayasu arteritis: a web-based survey in a large cohort.Frontiers in immunology · 2023Article
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10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmunocompromised populations, such as organ transplant recipients and patients with inflammatory bowel disease (IBD) receiving immunosuppressive/immunomodulatory medications, may be more susceptible to coronavirus infections. However, little is known about how immunosuppressants affect coronavirus replication and their combinational effects with antiviral drugs.
objectiveThis study aims to profile the effects of immunosuppressants and the combination of immunosuppressants with oral antiviral drugs molnupiravir and nirmatrelvir on pan-coronavirus infection in cell and human airway organoids (hAOs) culture models.
methodsDifferent coronaviruses (including wild type, delta and omicron variants of SARS-CoV-2, and NL63, 229E and OC43 seasonal coronaviruses) were used in lung cell lines and hAOs models. The effects of immunosuppressants were tested.
resultsDexamethasone and 5-aminosalicylic acid moderately stimulated the replication of different coronaviruses. Mycophenolic acid (MPA), 6-thioguanine (6-TG), tofacitinib and filgotinib treatment dose-dependently inhibited viral replication of all tested coronaviruses in both cell lines and hAOs. The half maximum effective concentration (EC50) of tofacitinib against SARS-CoV-2 was 0.62 μM and the half maximum cytotoxic concentration (CC50) was above 30 μM, which resulted in a selective index (SI) of about 50. The anti-coronavirus effect of the JAK inhibitors tofacitinib and filgotinib is dependent on the inhibition of STAT3 phosphorylation. Combinations of MPA, 6-TG, tofacitinib, and filgotinib with the oral antiviral drugs molnupiravir or nirmatrelvir exerted an additive or synergistic antiviral activity.
conclusionsDifferent immunosuppressants have distinct effects on coronavirus replication, with 6-TG, MPA, tofacitinib and filgotinib possessing pan-coronavirus antiviral activity. The combinations of MPA, 6-TG, tofacitinib and filgotinib with antiviral drugs exerted an additive or synergistic antiviral activity. Thus, these findings provide an important reference for optimal management of immunocompromised patients infected with coronaviruses.
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