Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection
Fantini et al.,
Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and..,
Int J Antimicrob Agents, 55:5, doi:10.1016/j.ijantimicag.2020.105960 (Theory)
In Silico analysis confirming the antiviral properties of CQ, showing a new mechanism of action of CQ, and showing that HCQ is more potent than CQ.
Fantini et al., 3 Apr 2020, peer-reviewed, 4 authors.
Abstract: Since January 2020 Elsevier has created a COVID-19 resource centre with
free information in English and Mandarin on the novel coronavirus COVID19. The COVID-19 resource centre is hosted on Elsevier Connect, the
company's public news and information website.
Elsevier hereby grants permission to make all its COVID-19-related
research that is available on the COVID-19 resource centre - including this
research content - immediately available in PubMed Central and other
publicly funded repositories, such as the WHO COVID database with rights
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 free by Elsevier for as long as the COVID-19 resource centre
remains active.
International Journal of Antimicrobial Agents 55 (2020) 105960
Contents lists available at ScienceDirect
International Journal of Antimicrobial Agents
journal homepage: www.elsevier.com/locate/ijantimicag
Structural and molecular modelling studies reveal a new mechanism
of action of chloroquine and hydroxychloroquine against SARS-CoV-2
infection
Jacques Fantini a,b,∗, Coralie Di Scala c, Henri Chahinian a,b, Nouara Yahi a,b
a
b
c
INSERM UMR_S 1072, Marseille, France
Department of Biology, Aix-Marseille Université, Marseille, France
INMED, INSERM U1249, Parc Scientifique de Luminy, Marseille, France
a r t i c l e
i n f o
Editor: Jean-Marc Rolain
Keywords:
Coronavirus
Pandemic
SARS-CoV-2
Ganglioside
Spike
Chloroquine
a b s t r a c t
The recent emergence of the novel pathogenic SARS-coronavirus 2 (SARS-CoV-2) is responsible for a
worldwide pandemic. Given the global health emergency, drug repositioning is the most reliable option
to design an efficient therapy for infected patients without delay. The first step of the viral replication
cycle [i.e. attachment to the surface of respiratory cells, mediated by the spike (S) viral protein] offers
several potential therapeutic targets. The S protein uses the angiotension-converting enzyme-2 (ACE-2)
receptor for entry, but also sialic acids linked to host cell surface gangliosides. Using a combination of
structural and molecular modelling approaches, this study showed that chloroquine (CLQ), one of the
drugs currently under investigation for SARS-CoV-2 treatment, binds sialic acids and gangliosides with
high affinity. A new type of ganglioside-binding domain at the tip of the N-terminal domain of the SARSCoV-2 S protein was identified. This domain (111–158), which is fully conserved among clinical isolates
worldwide, may improve attachment of the virus to lipid rafts and facilitate contact with the ACE-2 receptor. This study showed that, in the presence of CLQ [or its more active derivative, hydroxychloroquine
(CLQ-OH)], the viral S protein is no longer able to bind gangliosides. The identification of this new mechanism of action of CLQ and CLQ-OH supports the use of these repositioned drugs to cure patients infected
with SARS-CoV-2. The in-silico approaches used in this study might also be used to assess the efficiency
of a broad range of repositioned and/or innovative drug candidates before clinical evaluation.
© 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Please send us corrections, updates, or comments. Vaccines and
treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, or intervention
is 100% available and effective for all current and future variants. We do not
provide medical advice. Before taking any medication, consult a qualified
physician who can provide personalized advice and details of risks and
benefits based on your medical history and situation.
FLCCC and
WCH
provide treatment protocols.
Submit