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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
Mar 2021  
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Ivermectin for COVID-19
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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.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), inhibits SARS-CoV-2 3CLpro Mody, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing Fauquet, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, Scheim, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation Liu (C), shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), increases Bifidobacterium which plays a key role in the immune system Hazan, has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.
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.
This PaperIvermectinAll
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
Virus Research, doi:10.1016/j.virusres.2021.198384
In vitro testing Bovine coronavirus Bovine viral diarrhea virus Bovine respiratory syncytial virus Bovine parainfluenza type 3 virus Bovine herpesvirus type 1 A B S T R A C T 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 occasions. 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.
Experiment no Target Treatment Viral titers (Log10 TCID 50 )* BRSV BPIV-3 BoHV-1 BCoV BVDV #2 Virus attachment Non-treated 10 6.75 10 7.00 10 5.75 10 4.50 10 5.50 IVM-treated 10 6.75 10 6.75 10 5.50 10 4.50 10 5.50 #3 Virus penetration Non-treated 10 5.50 10 6.50 10 5.75 10 4.75 10 3.50 IVM-treated 10 5.25 10 6.50 10 5.25 10 4.25 10 2.75 * No statistical significance was observed between titers obtained from treated and non-treated experiments of the particular virus species. Author statement Kadir Yesilbag: Conceptualization, Methodology, Supervising, Writing, Redactions, Funding acquisition. Eda Baldan Toker: Writing-Original draft preparation, Validation, Investigation, Formal analysis Ozer Ates: Resource, Investigation. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi: 1016/j.virusres.2021.198384.
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