Effects of chloroquine on viral infections: an old drug against today's diseases
et al., Lancet Infect. Dis.,
Discussion/review noting that CQ exerts antiviral effects, inhibiting the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Notes that CQ has immunomodulatory effects, suppressing the production/release of tumour necrosis factor α and interleukin 6, which mediate the inflammatory complications of several viral diseases.
Savarino et al., 1 Nov 2003, peer-reviewed, 5 authors.
Abstract: Personal view
Antiviral effects of chloroquine
Effects of chloroquine on viral infections: an old
drug against today’s diseases?
Andrea Savarino, Johan R Boelaert, Antonio Cassone, Giancarlo Majori, and Roberto Cauda.
Chloroquine is a 9-aminoquinoline known since 1934. Apart
from its well-known antimalarial effects, the drug has
interesting biochemical properties that might be applied
against some viral infections. Chloroquine exerts direct
antiviral effects, inhibiting pH-dependent steps of the
replication of several viruses including members of the
flaviviruses, retroviruses, and coronaviruses. Its best-studied
effects are those against HIV replication, which are being
tested in clinical trials. Moreover, chloroquine has immunomodulatory effects, suppressing the production/release of
tumour necrosis factor and interleukin 6, which mediate the
inflammatory complications of several viral diseases. We
review the available information on the effects of chloroquine
on viral infections, raising the question of whether this old
drug may experience a revival in the clinical management of
viral diseases such as AIDS and severe acute respiratory
syndrome, which afflict mankind in the era of globalisation.
Endocytosis of viral particles
in the Golgi
Lancet Infect Dis 2003; 3: 722–27
Chloroquine is a 9-aminoquinoline that has been known
since 1934. Specifically synthesised to be used as an
antimalarial agent, chloroquine was subsequently shown to
have immunomodulatory properties that have encouraged
its application in the treatment of autoimmune diseases
such as rheumatoid arthritis. For this specific pathology,
chloroquine and its hydroxy-analogue hydroxychloroquine
have represented a valid contribution to the available
pharmacological tools, since they proved able to slow down
the progress of the disease while showing limited toxicity.1
Unfortunately, chloroquine is being gradually dismissed
from antimalarial therapy and prophylaxis, due to the
continuous emergence of chloroquine-resistant Plasmodium
falciparum strains. However, the tolerability, low cost, and
immunomodulatory properties of chloroquine/hydroxychloroquine are associated with biochemical effects that
suggest a potential use in viral infections, some of whose
symptoms may result from the inflammatory response.2,3 We
raise the question of whether this old drug whose parent
compound, quinine, was isolated in the late 19th century
from the bark of the tropical cinchona tree, may experience a
revival in the clinical management of viral diseases of the era
General biochemical and cellular effects of
Both chloroquine and hydroxychloroquine are weak bases
that are known to affect acid vesicles leading to dysfunction
of several enzymes. Extracellularly, chloroquine/hydroxychloroquine is present mostly in a protonated form that, due
Transport of newly
formed viral particles
Exocytosis of viral particles
Figure 1. Steps of the replication of different viruses affected by
chloroquine (marked by red rectangles). Chloroquine inhibits the replication
of different viruses either at the early or late stages of viral replication.
to its positive charge, is incapable of crossing the plasma
membrane. However, the non-protonated..
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