Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK

Kono et al., Antiviral Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011 (In Vitro)

Kono et al., Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine:.., Antiviral Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011 (In Vitro)

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CQ significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. CQ affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). p38 MAPK inhibitor, SB203580, inhibits CPE induced by HCoV-229E infection and viral replication.

14 In Vitro studies support the efficacy of HCQ [Andreani, Clementi, Dang, Delandre, Faísca, Hoffmann, Liu, Ou, Purwati, Sheaff, Wang, Wang (B), Yao, Yuan].

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1. Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228, In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, https://www.sciencedirect.com/science/article/pii/S0882401020305155.

2. Clementi et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (preprint 3/31), Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro, https://www.frontiersin.org/articl..ign=ECO_FCIMB_XXXXXXXX_auto-dlvrit.

3. Dang et al., bioRxiv, doi:10.1101/2021.03.16.435741, Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein, https://www.biorxiv.org/content/10.1101/2021.03.16.435741v1.

4. Delandre et al., Pharmaceuticals, doi:10.3390/ph15040445, Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants, https://www.mdpi.com/1424-8247/15/4/445.

5. Faísca et al., Pharmaceutics, doi:10.3390/pharmaceutics14040877, Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2, https://www.mdpi.com/1999-4923/14/4/877.

6. Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3, Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2, https://www.nature.com/articles/s41586-020-2575-3.

7. Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0, Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, https://www.nature.com/articles/s41421-020-0156-0.

8. Ou et al., PLOS Pathogens, doi:10.1371/journal.ppat.1009212 (preprint 7/22), Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2, https://journals.plos.org/plospath..le?id=10.1371/journal.ppat.1009212.

9. Purwati et al., PLOS One, doi:10.1371/journal.pone.0252302, An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia, https://journals.plos.org/plosone/..le?id=10.1371/journal.pone.0252302.

10. Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892, A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity, https://www.biorxiv.org/content/10.1101/2020.08.02.232892v1.

11. Wang et al., Phytomedicine, doi:10.1016/j.phymed.2020.153333, Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467095/.

12. Wang (B) et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, https://www.nature.com/articles/s4..iVs8_7R1KkwOuqjRhx7psfHV6iSDRD1cM0.

13. Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237, In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), https://academic.oup.com/cid/advan..le/doi/10.1093/cid/ciaa237/5801998.

14. Yuan et al., Communications Biology, doi:10.1038/s42003-022-03841-8, Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture, https://www.nature.com/articles/s42003-022-03841-8.

Kono et al., 4 Dec 2007, peer-reviewed, 6 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

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Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK

Masakazu Kono, Koichiro Tatsumi, Alberto M Imai, Kengo Saito, Takayuki Kuriyama, Hiroshi Shirasawa

Antiviral Research, doi:10.1016/j.antiviral.2007.10.011

The antiviral effects of chloroquine (CQ) on human coronavirus 229E (HCoV-229E) infection of human fetal lung cell line, L132 are reported. CQ significantly decreased the viral replication at concentrations lower than in clinical usage. We demonstrated that CQ affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). Furthermore, p38 MAPK inhibitor, SB203580, inhibits CPE induced by HCoV-229E infection and viral replication. Our findings suggest that CQ affects the activation of MAPKs, involved in the replication of HCoV-229E.

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