Insights from nanomedicine into chloroquine efficacy against COVID-19
Hu et al.,
Insights from nanomedicine into chloroquine efficacy against COVID-19,
Nature Nanotechnology, 15, 247–249, 2020, doi:10.1038/s41565-020-0674-9 (Theory)
CQ is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatment of COVID-19.
Hu et al., 23 Mar 2020, peer-reviewed, 3 authors.
Abstract: comment
Insights from nanomedicine into chloroquine
efficacy against COVID-19
Chloroquine — an approved malaria drug — is known in nanomedicine research for the investigation of
nanoparticle uptake in cells, and may have potential for the treatment of COVID-19.
Tony Y. Hu, Matthew Frieman and Joy Wolfram
R
ecent multicentre clinical trials1 and
cell culture studies2 suggest that the
70-year-old malaria drug, chloroquine,
may potentially display therapeutic efficacy
against COVID-19 (corona virus disease
2019), a rapidly spreading viral infection that
can cause pneumonia-induced death in
approximately 2.5% of infected individuals1,3.
Based on the preliminary clinical trial
findings, chloroquine has been included
in federal guidelines for treatment of
COVID-19 in the People’s Republic of
China. However, caution should be exercised
when making premature interpretations, as
clinical trials are still ongoing and interim
trial data have not yet been made available.
Given the current lack of an approved and
effective vaccine for severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2)1,
the virus causing COVID-19, it is important
to evaluate potential prophylactic and/or
therapeutic effects of drugs that are clinically
approved for other indications. Chloroquine
and its derivative, hydroxychloroquine,
have a long history as safe and inexpensive
drugs for use as prophylactic measures
in malaria-endemic regions and as daily
treatments for autoimmune diseases with the
most common side effect being eye damage
after long-term use4. Although previous
studies have revealed that chloroquine
has therapeutic activity against viruses5,
including human coronavirus OC43 in
animal models6 and SARS-CoV in cell
culture studies7, anti-viral mechanisms of
chloroquine remain speculative. Chloroquine
has been used in the field of nanomedicine
for the investigation of nanoparticle uptake
in cells, and, therefore, insights from
synthetic nanoparticle interactions with
cells in the presence of chloroquine may
reveal mechanisms that are active at early
stages prior to viral replication. Specifically,
nanomedicine studies may provide clues on
chloroquine-induced alterations of SARSCoV-2 cellular uptake.
Chloroquine mechanisms of action
The precise mechanisms through which
chloroquine may act to attenuate
SARS-CoV-2
Clathrin
Cell cytoplasm
Cell cytoplasm
PICALM
Chloroquine
Fig. 1 | Potential mechanism by which chloroquine exerts therapeutic effects against COVID-19.
The proposed mechanism involves chloroquine-induced suppression of PICALM, which prevents
endocytosis-mediated uptake of SARS-CoV-2.
SARS-CoV-2 infections are of considerable
interest, as this information could be
valuable for identifying new prophylactic
and therapeutic candidates. Chloroquine
is a weak base that becomes entrapped in
membrane-enclosed low pH organelles,
interfering with their acidification5. In
malaria-causing plasmodium parasites,
chloroquine accumulates in the digestive
vacuole where it is thought to prevent
pH-dependent detoxification of heme,
which is produced upon parasitic
consumption of haemoglobin to obtain
free amino acids8. This sequestering effect
is also apparent in mammalian cells, in
which chloroquine treatment leads to an
increase in lysosomal pH. Speculation
on chloroquine-induced antiviral effects
include inhibition of pH-dependent viral
fusion/replication and prevention of viral
envelope glycoprotein as well as host
receptor protein glycosylation5...
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