ROLE OF CHLOROQUINE IN CORONA VIRUS

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A letter of Understanding:
A Pilot Study to prevent the spreading of Middle
East Respiratory Syndrome using Chloroquine
Almonther Abdullah Hershan, AssistantProfessorof Molecular Medicine
(Virology), Jazan Faculty of Medicine, Jazan University
Mahmoud Ihab Mahmoud, MD, PhD Professor of Clinical Pharmacology,
Jazan Faculty of Medicine, Jazan University.
Mohamed Abdel Ghafaar, MD, consultantpulmonary, University Area
Hospital, Jeddah, KSA
Summary:
Middle East Respiratory Syndrome (MERS) was detected in Saudi
Arabia by 2012, since then it is spreading worldwide. WHO and
Saudi health authorities put the concern of this disease to be an
epidemic. The mortality rate is approximately 30% of the total
infection burden. The present study is mechanistically based to
prevent the spreading of the disease by inhibiting the budding of
the virus from infected cells. Chloroquine is a standard drug used
to treat malaria and other vesicles secretory diseases by disrupting
the acidic pH gradient necessary for Golgi operating condition. The
effect of chloroquine will be tested on pilot clinical trial to prove
this concept.
The letter of understanding is describing the rational and the aim
of the study and also to explore the potential for funding.

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Rationale and aim of work:
Middle East Respiratory Syndrome(MERS) is viralrespiratory infection; it
had been reported first in Saudi Arabia in 2012. Thecausative virus is
coronavirus, called MERS-CoV. The infected people express severeacute
respiratory illness with fever, cough, and shortness of breath. The mortality
rate of this infection is 30% particularly to vulnerable patients with chronic
diseases e.g. diabetes, hypertension, renal and heart problems, and others.
The situation is evolving and the spread of infection is giving an alarm to
epidemic spreading. The MERS Co-V has been detected not only in the
nearby countries of Saudi Arabia e.g. Qatar, Jordan, and the United Arab
Emirates but also cases havebeen reported in Yemen, Egypt…….. The
spreading of infection is linked to the visiting of the wholly places in KSA
(Makkah and Medina) and mainly among Muslims.
CDC is working with partners to better understand the risks of this virus,
including the source, how it spreads, and how infections might be
prevented. CDC has provided information for travelers and is working with
health departments, hospitals, and other partners to prepare for possible
cases in the United States.
The MERS virus becomes a national security issuefor KSA and requires
governmentaland international engagement to controlthe infection. On
April 24, 2014, theWorld Health Organization (WHO) issued a statement
indicating, "although camels are suspected to be the primary sourceof
infection for humans, the exact routes of direct or indirect exposure remain
unknown. Investigations to identify the sourceof infection and routes of
exposureare still ongoing."
Currently, it becomes an orphan disease for clinical trials. The understanding
of the cycle of infection in human and also an animal may shadelight for the
control.
The budding of the SARS-CoV occurs in the Golgi apparatus [1] and results in
the incorporation of the envelope spike glycoprotein into

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the virion. The spike glycoprotein is a type I membrane protein that
facilitates viralattachment to the cellular receptor and initiation of
infection. The budding vesicle across Golgiapparatus is moving from cis to
med and trans Golgi for exocytosis. This intracellular movement is going
across a low pH gradient. The hypothesis is to disruptthe acidic pH gradient
through a protonated species will stop the budding of the viron ad inhibit
the transmission of infection [2].
Chloroquine, a 9-aminoquinoline is a weak base that increases the pH of
acidic vesicles. The non-protonated portion of chloroquinepenetrates the
cell, whereit becomes protonated and concentrated in acidic, low-pH
organelles, such as endosomes, Golgivesicles, and lysosomes. Chloroquine
interrupts the intracellular virus infection in many ways, and its antiviral
effect depends in part on the extent to which the virus utilizes endosomes
for entry [3]
This mechanismof chloroquinehas been exploited to treat human diseases,
such as malaria, amoebiosis, HIV, and autoimmune diseases, without
significant detrimental side effects [4].
chloroquinein animal models of SARS-CoV infection would be warranted as
we progress toward finding effective antivirals for prevention or treatment
of the disease.
The aim of this letter of understanding is to explore the possibility to test
the effect of chloroquineto inhibit the spreading of infection od MERS Co-V
References:
1- Ng ML, Tan SH, See EE, Ooi EE, Ling AE: Proliferativegrowth of
SARS coronavirus in Vero E6 cells. J Gen Virol2003, 84:3291-3303.
2-Nicolas Demaurex, Wendy Furuya, Sudhir D’Souza, Juan S. Bonifacino
and Sergio Grinstein. Mechanism of Acidification of the trans-GolgiNetwork
(TGN) INSITUMEASUREMENTS OF pH USING RETRIEVAL OF TGN38 AND
FURINFROMTHE CELL SURFACE., Journalof BiologicalChemistry, 1998,
273, 2044-2051.

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3- Martin J Vincent, Eric Bergeron, SuzanneBenjannet, Bobbie R Erickson,
Pierre E Rollin, Thomas G Ksiazek, Nabil G Seidah and Stuart T Nichol.
Chloroquine is a potent inhibitor of SARS coronavirus infection and
Spread. Virology Journal2005, 2:69-79
4- Savarino A, Boelaert JR, CassoneA, MajoriG, Cauda R: Effects of
chloroquineon viral infections: an old drug against today's
diseases? Lancet InfectDis 2003, 3:722-727.