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Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19

Surnar et al., ACS Pharmacol. Transl. Sci., doi:10.1021/acsptsci.0c00179
Dec 2020  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
*, now with p < 0.00000000001 from 104 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments.
In Vitro analysis of ivermectin with orally administrable nanoparticles showing efficacy for decreasing expression of the viral spike protein and ACE2. Inhibition of nuclear transport activities mediated through proteins such as importin α/β1 heterodimer are also considered as a possible mechanism of action. The technology may work for other coronaviruses as well.
68 preclinical studies support the efficacy of ivermectin for COVID-19:
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N766, Dengue32,67,68, HIV-168, Simian virus 4069, Zika32,70,71, West Nile71, Yellow Fever72,73, Japanese encephalitis72, Chikungunya73, Semliki Forest virus73, Human papillomavirus52, Epstein-Barr52, BK Polyomavirus74, and Sindbis virus73.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins66,68,69,75, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing33, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination36,76, shows dose-dependent inhibition of wildtype and omicron variants31, exhibits dose-dependent inhibition of lung injury56,61, may inhibit SARS-CoV-2 via IMPase inhibition32, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation5, inhibits SARS-CoV-2 3CLpro49, may inhibit SARS-CoV-2 RdRp activity24, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages55, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation77, may inhibit SARS-CoV-2 by disrupting CD147 interaction78-81, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1954,82, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage4, may minimize SARS-CoV-2 induced cardiac damage35,43, increases Bifidobacteria which play a key role in the immune system83, has immunomodulatory46 and anti-inflammatory65,84 properties, and has an extensive and very positive safety profile85.
Surnar et al., 4 Dec 2020, peer-reviewed, 4 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19
Bapurao Surnar, Mohammad Z Kamran, Anuj S Shah, Shanta Dhar
ACS Pharmacology & Translational Science, doi:10.1021/acsptsci.0c00179
There is urgent therapeutic need for COVID-19, a disease for which there are currently no widely effective approved treatments and the emergency use authorized drugs do not result in significant and widespread patient improvement. The food and drug administration-approved drug ivermectin has long been shown to be both antihelmintic agent and a potent inhibitor of viruses such as Yellow Fever Virus. In this study, we highlight the potential of ivermectin packaged in an orally administrable nanoparticle that could serve as a vehicle to deliver a more potent therapeutic antiviral dose and demonstrate its efficacy to decrease expression of viral spike protein and its receptor angiotensin-converting enzyme 2 (ACE2), both of which are keys to lowering disease transmission rates. We also report that the targeted nanoparticle delivered ivermectin is able to inhibit the nuclear transport activities mediated through proteins such as importin α/β1 heterodimer as a possible mechanism of action. This study sheds light on ivermectin-loaded, orally administrable, biodegradable nanoparticles to be a potential treatment option for the novel coronavirus through a multilevel inhibition. As both ACE2 targeting and the presence of spike protein are features shared among this class of virus, this platform technology has the potential to serve as a therapeutic tool not only for COVID-19 but for other coronavirus strains as well.
Notes The authors declare no competing financial interest. ■ ACKNOWLEDGMENTS This work was supported by the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine. We thank Shrita Sarkar for her help for the illustration of Figure 1 and Dr. Nagesh Kolishetti for helpful discussion.
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res, doi:10.1016/j.antiviral.2020.104787
Dashraath, Wong, Lim, Lim, Li et al., Coronavirus disease 2019 (COVID-19) pandemic and pregnancy, Am. J. Obstet. Gynecol, doi:10.1016/j.ajog.2020.03.021
Elkassaby, Ivermectin uptake and distribution in the plasma and tissue of Sudanese and Mexican patients infected with Onchocerca volvulus, Trop. Med. Parasitol
Gheblawi, Wang, Viveiros, Nguyen, Zhong, None
Heidary, Gharebaghi, Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen, J. Antibiot, doi:10.1038/s41429-020-0336-z
Li, Geng, Peng, Meng, Lu, Molecular immune pathogenesis and diagnosis of COVID-19, J. Pharm. Anal, doi:10.1016/j.jpha.2020.03.001
Li, He, Zhang, Ran, Wang et al., Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19, J. Autoimmun, doi:10.1016/j.jaut.2020.102463
Mastrangelo, Pezzullo, De Burghgraeve, Kaptein, Pastorino et al., Ivermectin Is a Potent Inhibitor of Flavivirus Replication Specifically Targeting NS3 Helicase Activity: New Prospects for an Old Drug, J. Antimicrob. Chemother, doi:10.1093/jac/dks147
Mcgonagle, Sharif, O'regan, Bridgewood, The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease, Autoimmun. Rev, doi:10.1016/j.autrev.2020.102537
Merad, Martin, Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages, Nat. Rev. Immunol, doi:10.1038/s41577-020-0331-4
Ou, Liu, Lei, Li, Mi et al., Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV, Nat. Commun, doi:10.1038/s41467-020-15562-9
Pandey, Khan, Kumar, Srivastava, Jha, Screening of Potent Inhibitors Against 2019 Novel Coronavirus (Covid-19) from Alliumsativum and Allium cepa: An In Silico Approach, Biointerface Res. Appl. Chem, doi:10.33263/BRIAC111.79817993
Pandey, Khan, Rana, Srivastava, Jha et al., A Drug Repurposing Approach Towards Elucidating the Potential of Flavonoids as COVID-19 Spike Protein Inhibitors, Biointerface Res. Appl. Chem, doi:10.33263/BRIAC111.84828501
Qin, Zhou, Hu, Zhang, Yang et al., Dysregulation of immune response in patients with COVID-19 in Wuhan, China, Clin. Infect. Dis, doi:10.1093/cid/ciaa248
Rowland, Chauhan, Fang, Pekosz, Kerrigan et al., Intracellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein: absence of nucleolar accumulation during infection and after expression as a recombinant protein in Vero cells, J. Virol, doi:10.1128/JVI.79.17.11507-11512.2005
Singh, Chaubey, Chen, Suravajhala, Decoding SARS-CoV-2 hijacking of host mitochondria in COVID-19 pathogenesis, Am. J. Physiol Cell Physiol, doi:10.1152/ajpcell.00224.2020
Sungnak, Huang, Becavin, Berg, Queen et al., None
Surnar, Kamran, Shah, Basu, Kolishetti et al., Orally Administrable Therapeutic Synthetic Nanoparticle for Zika Virus, ACS Nano, doi:10.1021/acsnano.9b02807
Timani, Liao, Ye, Zeng, Liu et al., Nuclear/ nucleolar localization properties of C-terminal nucleocapsid protein of SARS coronavirus, Virus Res, doi:10.1016/j.virusres.2005.05.007
Turner, Raizada, Grant, Oudit, Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System, Circ. Res, doi:10.1161/CIRCRESAHA.120.317015
Wagstaff, Rawlinson, Hearps, Jans, None
Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem. J, doi:10.1042/BJ20120150
Wang, Du, Huang, Wei, Wu et al., The Pseudorabies Virus DNA Polymerase Accessory Subunit UL42 Directs Nuclear Transport of the Holoenzyme, Front. Microbiol, doi:10.3389/fmicb.2016.00124
Wulan, Heydet, Walker, Gahan, Ghildyal, Nucleocytoplasmic transport of nucleocapsid proteins of enveloped RNA viruses, Front. Microbiol, doi:10.3389/fmicb.2015.00553
Yan, Zhang, Li, Xia, Guo et al., Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2, Science, doi:10.1126/science.abb2762
Yang, Atkinson, Wang, Lee, Bogoyevitch et al., The broad spectrum antiviral ivermectin targets the host nuclear transport importin alpha/ beta1 heterodimer, Antiviral Res, doi:10.1016/j.antiviral.2020.104760
Yuki, Fujiogi, Koutsogiannaki, COVID-19 pathophysiology: A review, Clin. Immunol, doi:10.1016/j.clim.2020.108427
Zhang, Penninger, Li, Zhong, Slutsky, Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target, Intensive Care Med, doi:10.1007/s00134-020-05985-9
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