Chloroquine has been found to be effective against many viral infections in vitro through several proposed mechanisms: 1) it blocks viral replication by increasing endosomal pH required for viral fusion and uncoating, 2) it acts as a zinc ionophore inhibiting viral RNA polymerase, and 3) it modulates the immune response by reducing cytokine release. Recent studies demonstrate chloroquine can effectively inhibit SARS-CoV-2 in vitro, possibly by blocking viral entry. While chloroquine may have potential for COVID-19 treatment or prophylaxis, further randomized controlled trials are still needed to validate its risks and benefits for this application.

1. CHLOROQUINE- A RESCUE DRUG FROM COVID 19 PANDEMIC?
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Dr. Alimi, H.A.
MB;BS, Lagos

2. USES
• Chloroquine and its hydroxylated form have been found to be
effective against many conditions aside the malaria fever for
which its no longer a drug of choice.
• They have been used for the management of infectious
diseases such as
 Acute Q fever
 Amoebiasis
 Whipple disease
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3. USES
They have also be found useful for conditions such as
sarcoidosis
porphyria cutanea tarda
calcium pyrophosphate deposition disease
connective tissue diseases and
myopathies.
Hydroxyl chloroquine is preferred for long time use due to a
more favourable side effect profile.
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4. ANTI-VIRAL EFFECT
• The antiviral effect of chloroquine is well established in
laboratory studies.
• Many RNA viruses as well as some DNA viruses have
been found susceptible in vitro.
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5. PROPOSED ANTI VIRAL MECHANISMS
BLOCKS VIRAL REPLICATION
Zn IONOPHORE
MODULATION OF THE IMMUNE RESPONSE
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7. HOW CHLOROQUINE BLOCKS VIRAL
REPLICATION
Induction of endosomal-lysosomal dysfunction
chloroquine is a weak diprotic weak base which has
high affinity for intracellular vacuoles especially
endosomes and lysosomes.
It increases the intracellular pH(alkalinization) of
these vacuoles altering their normal function, viz a
viz protein breakdown, synthesis of
macromolecules, post-translational modification of
chemical substrates.
It should be noted that these vacuoles work best
under low pH conditions.
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8. Chloroquine as Zn ionophore
• Chloroquine permits zinc to enter cells.
• It is believed that accumulation of Zinc within the
cell inhibit viral RNA dependent RNA polymerase.
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9. As a modulator of immune response
 Chloroquine limits exaggerated response of the immune
response to viral assault. This makes sense particularly
considering the cytokine storm hypothesis that have been put
forward to explain severe viral assault.
 Chloroquine achieve this by reducing the release of cytokines
such as IL - 1, IL - 2 and TNF alpha.
 There are also reports that it inhibits lymphocyte proliferation,
and release of reactive oxygen species from macrophages.
 This may be the major reason why chloroquine is effective in
viral pneumonia.
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10. Chloroquine Vs Coronavirus
• Wang et al., (2020) demonstrated that chloroquine, in vitro, at small doses
blocks viral infection and showed high selectivity index for SARS-COV 2.
• This can be partly explain by the fact that coronavirus enter cell via
endolysosomal pathway which is disrupted by the chloroquine molecule.
• Disruption of sialic acid synthesis is another way chloroquine inhibits viral
ligand-host receptor (those requiring sialic moieties) interaction and hence viral
entry is prevented. This may not be applicable to SARS- COV 2.
• Overall, the fact that it blocks viral infection may form the scientific basis for
prophylactic use.
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11. DRUG CHARACTERISTICS
• Oral dose is rapidly absorbed and largely excreted by the
kidneys.
• Chloroquine has a large volume of distribution
• It’s narrow therapeutic index and long half life of almost 1
to 2months can be particular problematic in the face of
acute toxicity.
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12. Side effect profile
Experience with the drug has made it possible for its side effect to be more or
less common knowledge among physicians.
 Eye: Visual impairment may ensue with chronic use. Chloroquine causes
visual loss either through retinopathy, macular keratopathy and/ or
disturbance in accommodation.
 Skin: perhaps pruritus is the most recognized side effects especially in dark
patients. It may cause alopecia and exacerbate psoriasis.
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13. Side effect profile cont'd
 Cardiovascular effects: chronic use has been linked to AV block and dilated
cardiomyopathy. However, its QT prolongation effect makes it a nightmare for
cardiac patients. It can also cause postural hypotension.
 Hematological issues: aplastic anemia, agranulocytosis and
thrombocytopenia.
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14. Side effect profile cont'd
 Neurological effects: It may cause peripheral neuropathy, seizures, tinnitus,
ototoxicity, dysphoria and neuropsychiatric reactions.
 Acute toxicity may present with fatal cardiac arrhythmia, electrolyte
derangement especially hypokalaemia, seizures, and even death. It is often
managed with epinephrine, diazepam and mechanical ventilation.
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15. Conclusion
• Chloroquine is an old drug with many applications in
medicine.
• Its antiviral effects has been demonstrated in vitro.
• There is evidence to suggest prophylactic use as well as
to treat SARS-COV 2. However, the risk-benefit ratio
must be considered.
• RCTs will still be required to verify these assertions.
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16. REFERENCES
• Philippe Colson, Jean-Marc Rolain, Jean-Christophe Lagier, Philippe Brouqui, Didier Raoult.
(2020)Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. International
Journal of Antimicrobial Agents https://doi.org/10.1016/j.ijantimicag.2020.105932.
• Wang, M., Cao, R., Zhang, L. et al. (2020) Remdesivir and chloroquine effectively inhibit the recently
emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30, 269–271 .
https://doi.org/10.1038/s41422-020-0282-0.
• Andrea Cortegiani, Giulia Ingoglia, Mariachiara Ippolito, Antonino Giarratano, Sharon Einav, (2020) A
systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. Journal of
Critical Care https://doi.org/10.1016/j.jcrc.2020.03.005.
• Harrison's Principles of Internal Medicine, 20e. New York, NY: McGraw-Hill
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