CHLOROQUINE AND HYDROXYCHLOROQUINE ARE AVAILABLE TREATMENT OPTIONS TO FIGHT WITH COVID-19

Basrah Journal of Veterinary Research,Vol.19, No.3, 2020. Proceeding of the 17th International Conference. College of
Veterinary Medicine. University of Basrah. Iraq.
297
CHLOROQUINE AND HYDROXYCHLOROQUINE ARE AVAILABLE
TREATMENT OPTIONS TO FIGHT WITH COVID-19
Shadia S. Alhamd* , Manal I. khaleel*
*Department of Biology,College of Education for Pure Sciences,University of Basrah, Iraq .
Corresponding Author : [email protected]
Key words: Chloroquine (CQ), Hydroxychloroquine (HCQ), SARS-CoV-2.
ABSTRACT
The corona virus SARS-CoV-2 caused pandemic Covid-19 disease. At present there is no
vaccine or drug approved by FDA to treat Covid-19 disease. The high fatality rate and extreme
fast spreading of disease in the community make researchers to invent possible therapeutic
inventions a global priority. Recent studies suggested that Chloroquine (ChQ) and
Hydroxychloroquine (HChQ) can be used for the treatment of Covid-19 patients. In-vitro tests
suggest ChQ and HChQ have good efficiency towards SARS-CoV-2 virus. In this report, we
have reviewed latest literature information about ChQ and HChQ drugs to use for the treatment
of this pandemic.
INTRODUCTION
The epidemic of corona virus was declared for the first time in 2019 December in
Wuhan city of China. This is a new SARS-CoV-2 virus which belongs to corona family. On 7th
January, 2020, there was an official announcement from Chinese health officials related to
discovery of carona virus. By this time the new virus SARS-CoV-2 affected 11 million people in
the Wuhan metropolis city. Later on 30th January 2020 the World Health Organization (WHO)
officially declared health emergency globally. Later WHO named the disease caused by this
novel virus as Covid-19. Due to the exponential increase of virus effected patients globally the
WHO upgraded the situation epidemic to pandemic on 11th March 2020 (1, 2).
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The SARS-CoV-2 virus main target in the diseased patients is lower respiratory tract
which cause cold, cough and throat infections. Serious symptoms such as difficulty in breathing
or shortness of breath and chest pain appeared in the Covid-19 patients. On average it takes 5-6
days to observe the symptoms from when someone is infected with the virus; however it can take
up to 14 days. It is notable that adult patients with Covid-19 in early stage, observed with a keen
decrease in CD4+ and CD8+ T-cell subsets (3, 4).
Accordingly the victims suffered with acute respiratory distress condition for 7 to 10 days
after infected with Covid-19 due to the swift growth of virus in the body. The virus replication in
the body also increases the pro-inflammatory cytokines as well as chemokine response and
inflammatory cell infiltrates (4, 5). The incubation period of SARS-CoV-2 virus differs from 2
days to 14 days in different persons, the vague incubation period make it difficult for early
diagnosis. The late diagnosis affecting more on the community spread and majorly initiation of
treatment in early stage of disease (5, 6).
Epidemiology of corona virus:
After an epidemic breakout in China in January of 2020 the outbreak status has been
advanced internationally with the rapid growth in South Korea, Singapore and Japan. Soon after
researchers noticed rapid growth of Covid-19 affected patients in Italy and Iran. In the above
countries it is witnessed as a community transmission with the persons came from China. The
number of Covid-19 patients reached to peak after two months the virus appeared in China. In
March first week the Chinese officials declared that the number of new patients are decreasing
actively in the country and government reopened the public places. However by that time all the
European countries are badly affected with the corona virus (1),
Precisely Italy, Span and France countries. By the March 16th the WHO announced
almost as many cases appeared in China are appeared worldwide with 81,077 Covid-19 patients
in China and 86,438 patient’s rest of the world which includes 143 countries. The WHO
announced that as of May 11th 2020, there were 4,088,848 confirmed Covid-19 cases and
283,153 deaths.
Treatment options:
Basrah Journal of Veterinary Research,Vol.19, No.3, 2020. Proceeding of the 17th International Conference. College of
Veterinary Medicine. University of Basrah. Iraq.
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The center of Disease control and prevention (CDC) on 21st March 2020 in a public
document informed that there is no vaccine or precise medicine for SARS-CoV-2 (7). The
speedy outbreak of corona virus worldwide and the distressing more number of deaths
encouraged the scientific community accelerates the invention of all possible and innovative
controlling methods of this disease( 8).
Quite a few interventional treatment options come up for controlling Covid-19 disease
with indefinite efficiency and safety measures (9). Recent studies recommended a well-known
anti-malarial drug Chloroquine (ChQ) and Hydroxychloroquine (HChQ) to treat the Covid-19
patients. These FDA approved drugs are used to treat malaria and specific inflammatory
conditions at present. In this epidemic situation WHO lists ChQ and HChQ as essential drugs, so
these medicines should be available all times in affordable price (10, 11).The ChQ and HChQ
molecules showed in-vitro activity against SARS-CoV, SARS-CoV-2, and other corona viruses.
It is reported that the HChQ is having relatively high potency than ChQ against SARS-CoV-2
virus (12-14).
Figure 1: The chemical structures of Chloroquine and Hydroxychloroquine
Chloroquine and hydroxychloroquine antiviral activities against COVID-19
The ChQ and HChQ have chemical structure similarities and they are approved by FDA
for anti-malarial and anti-rheumatic treatment. For the literature these drugs also known for their
antiviral activity with various mechanisms (15- 17). In this epidemic outbreak, ChQ and HChQ
have been proposed as anti-SARS-CoV-2 drugs as ChQ inhibited the virus in cell culture
Basrah Journal of Veterinary Research,Vol.19, No.3, 2020. Proceeding of the 17th International Conference. College of
Veterinary Medicine. University of Basrah. Iraq.
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experiments (18, 19), and they also emerge to decrease virus growth in Covid-19 patients in an
open label non-randomized trail (20).
These drugs showed excellent anti-viral properties in-vitro, with its effect on primitive
stages of virus replication through preventing virus-endosome fusion, by growing endosomal pH
(21). It is shown that Corona viruses are able to reach the target cells using pH dependent
mechanism, while acidic pH of lysosome results in to fusion of virus and endosomal membranes.
It is known that results of uncoating of viral particle and successively viral nucleic acid release in
the cytoplasm (22). The ChQ also damages the post translational alterations of virus proteins by
interfering with prolytic processes (23). ChQ also shows inhibition of glycosylation through
inhibiting sugar modifying enzymes or glycosyltransferases (24).
Previous studies show that ChQ molecule inhibits the access of the SARS-CoV into
human cells by interfering with the glycosylation of its cellular receptor angiotensin converting
enzyme 2 receptor (ACE2). Recent literature reveals that SARS-CoV-2 also enters into the
human body through ACE2 receptor. This suggests that a possible inhibition effect of ChQ on
SARS-CoV-2 at this viral replication step (25). On the other hand, because of its antiinflammatory
activity ChQ and HChQ drugs are used to treat multiple diseases where
inflammation is effect such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA)
and osteoarthritis (26). In this regard, the central symptom of COVID-19, the virus induces lungs
inflammation, this symptom can be an advantageous effect of ChQ and HChQ as both the drugs
have capacity to reduce the inflammation.
Efficacy and Toxicity
The ChQ drug in-vitro tests on Vero E6 cells infected by SARS-CoV-2 showing the EC90
of 6.90 μM, is became a promising choice of using ChQ in clinical treatment of SARS-CoV-2 as
completely off-label (27). On the other hand, HChQ drug is considerably more effective compare
to ChQ was observed in vitro results as the EC50 values of HChQ is 0.72 μM and ChQ is with
5.47 μM, and HChQ showing less efficiency for drug interactions in comparison to ChQ.
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Further, physiologically based pharmacokinetic models in vitro inhibition of SARS-COV-2
reveals that the drug molecule HChQ sulfate is showing better results around five days faster
than the drug ChQ phosphate (28).
The most common adverse effects of these two drugs are diarrhea, skin rashes, anorexia,
nausea (29), and a rare Acute Liver failure (30), a type of severe skin toxic epidermal necrolysis
(31) and Long QT syndrome along with cardiotoxicity (32-34).
Over many years people are using both Chloroquine and Hydroxychloroquine drugs in
treating the diseases like SLE and RA and these drugs are in the exhibit proper safety lines in
these diseases. HChQ is showing lesser toxicity in some of the animal studies, in comparison
with the usage of ChQ. Still there is no particular evidence of clinical trial to support the safety
levels of the HChQ molecule to compare the toxicity(35-38). It is require to consume larger
doses than the regular RA and SLE disease doses to treat SARS-CoV-2 and the effect of the
large doses will affect the health and may leads to side effects over the period of life.
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