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.