Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19
Surnar et al.,
Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19,
ACS Pharmacol. Transl. Sci., doi:10.1021/acsptsci.0c00179 (In Vitro)
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.
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].
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.
Abstract: This article is made available via the ACS COVID-19 subset for unrestricted RESEARCH re-use
and analyses in any form or by any means with acknowledgement of the original source.
These permissions are granted for the duration of the World Health Organization (WHO)
declaration of COVID-19 as a global pandemic.
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Article
Clinically Approved Antiviral Drug in an Orally Administrable
Nanoparticle for COVID-19
Bapurao Surnar, Mohammad Z. Kamran, Anuj S. Shah, and Shanta Dhar*
Cite This: ACS Pharmacol. Transl. Sci. 2020, 3, 1371−1380
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ABSTRACT: 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.
KEYWORDS: spike protein, severe acute respiratory syndrome virus, angiotensin-converting enzyme 2, RNA virus
trials, one aims to use the “wonder drug” ivermectin (IVM)14
in combination with aspirin, dexamethasone, and enoxaparin
(Table S2). This trial uses IVM via a single dose of 200 μg/kg
and may pose issues of toxicity and accelerated clearance from
the bloodstream resulting in low effective dose.15,16 In this
article, we report an orally administrable IVM-loaded nanoparticle (NP) and its ability to lower the expression of the
ACE2 receptor and the SARS-CoV-2 spike protein.
We recently developed a therapeutic IVM-loaded NP to
treat Zika virus infection in the blood.17 The developed IVM
nanoformulation allows the therapeutic to be gradually
released into the bloodstream, which maintains its level in
the blood at approximately the minimum effective therapeutic
dose while keeping it below the maximum tolerated dose. This
NP was constructed using poly(lactide-co-glycolide)-b-poly(ethylene glycol)-maleimide (PLGA-b-PEG-Mal) polymer,
and was tagged to an Fc immunoglobulin fragment to take
advantage of FcRn-driven crossing of the gut epithelial barrier
to reach the bloodstream (Figure 1A). Here, we adopted the
T
he COVID-19, a..
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