Yesilbag: Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro

Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro

Yesilbag et al., Virus Research, doi:10.1016/j.virusres.2021.198384 (In Vitro)

Yesilbag et al., Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV).., Virus Research, doi:10.1016/j.virusres.2021.198384 (In Vitro)

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In Vitro study showing that ivermectin can inhibit infection of bovine respiratory disease viral agents BCoV, BPIV-3, BVDV, BRSV and BoHV-1 at the concentrations of 2.5 and 5 μM and in a dose-dependent manner.

15 In Vitro studies support the efficacy of ivermectin [Boschi, Caly, Croci, De Forni, Delandre, Jeffreys, Jitobaom, Jitobaom (B), Li, Liu, Mody, Mountain Valley MD, Segatori, Surnar, Yesilbag].

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1. Boschi et al., bioRxiv, doi:10.1101/2022.11.24.517882, SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects, https://www.biorxiv.org/content/10.1101/2022.11.24.517882.

2. Caly et al., Antiviral Research, doi:10.1016/j.antiviral.2020.104787, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, https://www.sciencedirect.com/science/article/pii/S0166354220302011.

3. Croci et al., International Journal of Biomaterials, doi:10.1155/2016/8043983, Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin, http://www.hindawi.com/journals/ijbm/2016/8043983/.

4. De Forni et al., PLoS ONE, doi:10.1371/journal.pone.0276751, Synergistic drug combinations designed to fully suppress SARS-CoV-2 in the lung of COVID-19 patients, https://journals.plos.org/plosone/..le?id=10.1371/journal.pone.0276751.

5. 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.

6. Jeffreys et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2022.106542 (preprint 12/24/2020), Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2, https://www.sciencedirect.com/science/article/pii/S0924857922000309.

7. Jitobaom et al., BMC Pharmacology and Toxicology, doi:10.1186/s40360-022-00580-8 (preprint 11/30/2021), Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations, https://bmcpharmacoltoxicol.biomed..rticles/10.1186/s40360-022-00580-8.

8. Jitobaom (B) et al., Research Square, doi:10.21203/rs.3.rs-941811/v1, Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity against SARS-CoV-2, https://www.researchsquare.com/article/rs-941811/v1.

9. Li et al., J. Cellular Physiology, doi:10.1002/jcp.30055, Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment, https://onlinelibrary.wiley.com/doi/10.1002/jcp.30055.

10. Liu et al., bioRxiv, doi:10.1101/2022.01.20.477147, SARS-CoV-2 Viral Genes Compromise Survival and Functions of Human Pluripotent Stem Cell-derived Cardiomyocytes via Reducing Cellular ATP Level, https://www.biorxiv.org/content/10.1101/2022.01.20.477147.

11. Mody et al., Communications Biology, doi:10.1038/s42003-020-01577-x, Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents, https://www.nature.com/articles/s42003-020-01577-x.

12. Mountain Valley MD, Mountain Valley MD Receives Successful Results From BSL-4 COVID-19 Clearance Trial on Three Variants Tested With Ivectosol™, https://www.globenewswire.com/en/n..ariants-Tested-With-Ivectosol.html.

13. Segatori et al., Viruses, doi:10.3390/v13102084, Effect of Ivermectin and Atorvastatin on Nuclear Localization of Importin Alpha and Drug Target Expression Profiling in Host Cells from Nasopharyngeal Swabs of SARS-CoV-2- Positive Patients, https://www.mdpi.com/1999-4915/13/10/2084.

14. Surnar et al., ACS Pharmacol. Transl. Sci., doi:10.1021/acsptsci.0c00179, Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19, https://pubs.acs.org/doi/abs/10.1021/acsptsci.0c00179.

15. Yesilbag et al., Virus Research, doi:10.1016/j.virusres.2021.198384, Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro, https://www.sciencedirect.com/science/article/pii/S0168170221000915.

Yesilbag et al., 10 Mar 2021, peer-reviewed, 3 authors.

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

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Abstract: Virus Research 297 (2021) 198384 Contents lists available at ScienceDirect Virus Research journal homepage: www.elsevier.com/locate/virusres Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro Kadir Yesilbag *, Eda Baldan Toker, Ozer Ates Department of Virology, Bursa Uludag University, Faculty of Veterinary Medicine, 16059, Bursa, Turkey A R T I C L E I N F O A B S T R A C T Keywords: Ivermectin Antiviral efficiency In vitro testing Bovine coronavirus Bovine viral diarrhea virus Bovine respiratory syncytial virus Bovine parainfluenza type 3 virus Bovine herpesvirus type 1 Bovine respiratory disease (BRD) complex is an important viral infection that causes huge economic losses in cattle herds worldwide. However, there is no directly effective antiviral drug application against respiratory viral pathogens; generally, the metaphylactic antibacterial drug applications are used for BRD. Ivermectin (IVM) is currently used as a broad-spectrum anti-parasitic agent both for veterinary and human medicine on some oc casions. Moreover, since it is identified as an inhibitor for importin α/β-mediated nuclear localization signal (NLS), IVM is also reported to have antiviral potential against several RNA and DNA viruses. Since therapeutic use of IVM in COVID-19 cases has recently been postulated, the potential antiviral activity of IVM against bovine respiratory viruses including BRSV, BPIV-3, BoHV-1, BCoV and BVDV are evaluated in this study. For these purposes, virus titration assay was used to evaluate titers in viral harvest from infected cells treated with noncytotoxic IVM concentrations (1, 2.5 and 5 μM) and compared to titers from non-treated infected cells. This study indicated that IVM inhibits the replication of BCoV, BVDV, BRSV, BPIV-3 and BoHV-1 in a dose-dependent manner in vitro as well as number of extracellular infectious virions. In addition, it was demonstrated that IVM has no clear effect on the attachment and penetration steps of the replication of the studied viruses. Finally, this study shows for the first time that IVM can inhibit infection of BRD-related viral agents namely BCoV, BPIV-3, BVDV, BRSV and BoHV-1 at the concentrations of 2.5 and 5 μM. Consequently, IVM, which is licensed for antiparasitic indications, also deserves to be evaluated as a broad-spectrum antiviral in BRD cases caused by viral pathogens.

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