In this document i present to you some information of drugs which used to treat Covid-19. We know in 2020 Covid-19 turns very dengerous. I hope this document will help you a lot.

1. Southeast University
Drugs used to treat
Covid-19
Prepared by- Md. Mehedi Hasan Shawon
Department of Pharmacy
Southeast University, Banani, Dhaka, Bangladesh

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Contents
Introduction..................................................................................................................................... 3
Symptoms.................................................................................................................................... 3
Cause ........................................................................................................................................... 3
Treatment .................................................................................................................................... 3
Hydroxychloroquine ....................................................................................................................... 3
Chemistry.................................................................................................................................... 4
Mechanism of action................................................................................................................... 4
Synthesis...................................................................................................................................... 4
Metabolism.................................................................................................................................. 5
Favipiravir....................................................................................................................................... 5
Chemistry.................................................................................................................................... 5
Mechanism of action................................................................................................................... 5
Synthesis...................................................................................................................................... 6
Metabolism.................................................................................................................................. 6
Azithromycin .................................................................................................................................. 6
Chemistry.................................................................................................................................... 7
Mechanism of action................................................................................................................... 7
Synthesis...................................................................................................................................... 7
Metabolism.................................................................................................................................. 7
Ivermectin ....................................................................................................................................... 7
Chemistry.................................................................................................................................... 8
Mechanism of action................................................................................................................... 8
Synthesis...................................................................................................................................... 8
Metabolism.................................................................................................................................. 8
Dexamethasone ............................................................................................................................... 9
Chemistry.................................................................................................................................... 9
Mechanism of action................................................................................................................... 9
Synthesis...................................................................................................................................... 9

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Metabolism................................................................................................................................ 10
Chloroquine................................................................................................................................... 10
Chemistry.................................................................................................................................. 10
Mechanism of action................................................................................................................. 11
Synthesis.................................................................................................................................... 11
Metabolism................................................................................................................................ 11
Bibliography.................................................................................................................................. 11

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Introduction
Coronavirus disease 2019 (COVID-19) is defined as illness caused by a novel coronavirus now
called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly called 2019-
nCoV), which was first identified amid an outbreak of respiratory illness cases in Wuhan City,
Hubei Province, China. It was initially reported to the World Health Organization (WHO) on
December 31, 2019. On January 30, 2020, the WHO declared the COVID-19 outbreak a global
health emergency. On March 11, 2020, the WHO declared COVID-19 a global pandemic, its
first such designation since declaring H1N1 influenza a pandemic in 2009.
Symptoms
Fever is the most common symptom of COVID-19, but is highly variable in severity and
presentation, with some older, immunocompromised, or critically ill people not having fever at
all. Other common symptoms include cough, loss of appetite, fatigue, shortness of breath,
sputum production, and muscle and joint pains. Symptoms such as nausea, vomiting, and
diarrhea have been observed in varying percentages.
Cause
COVID-19 spreads primarily when people are in close contact and one person inhales small
droplets produced by an infected person (symptomatic or not) coughing, sneezing, talking, or
singing. The WHO recommends 1 metre (3 ft) of social distance; the U.S. CDC recommends 2
metres (6 ft). People can transmit the virus without showing symptoms, but it is unclear how
often this happens. One estimate of the number of those infected who are asymptomatic is 40%.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel severe acute
respiratory syndrome coronavirus, first isolated from three people with pneumonia connected to
the cluster of acute respiratory illness cases in Wuhan.
Treatment
Currently, no medication is recommended to treat COVID-19, and no cure is available.
Antibiotics aren't effective against viral infections such as COVID-19. Researchers are testing a
variety of possible treatments. There are some drugs which used in treatment of Covid -19. They
are: Ivermectin, Dexamethasone, Hydroxychloroquine, Chloroquine, Favipiravir, Avigan,
Azitromycin etc.
Hydroxychloroquine
Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to
prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses
include treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda. It is taken by
mouth.

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Chemistry
Hydroxychloroquine affects the function of lysozomes in humans as well as plasmodia. Altering
the pH of the lysozomes reduces low affinity self-antigen presentation in autoimmue diseases
and interferes with the ability of plasmodia to proteolyse hemoglobin for their energy
requirements. Hydroxychloroquine has a long duration of action as it may be taken on a weekly
basis for some indications. Hydroxychloroquine may lead to severe hypoglycemia and so
diabetic patients are advised to monitor their blood glucose levels. Hydroxychloroquine is not
effective against malaria in areas where chloroquine resistance has been reported.
Mechanismof action
The exact mechanisms of hydroxychloroquine are unknown. It has been shown that
hydroxychloroquine accumulates in the lysosomes of the malaria parasite, raising the pH of the
vacuole. This activity interferes with the parasite's ability to proteolyse hemoglobin, preventing
the normal growth and replication of the parasite. Hydroxychloroquine can also interfere with the
action of parasitic heme polymerase, allowing for the accumulation of the toxic product beta-
hematin. Hydroxychloroquine inhibits terminal glycosylation of ACE2, the receptor that SARS-
CoV and SARS-CoV-2 target for cell entry. ACE2 that is not in the glycosylated state may less
efficiently interact with the SARS-CoV-2 spike protein, further inhibiting viral entry.
Synthesis
The commercial HCQ synthesis employs a key intermediate, 5-(ethyl(2-
hydroxyethyl)amino)pentan-2-one (6), which is a major cost driver in the process. ... Scheme 2:
Retrosynthetic strategy to hydroxychloroquine. Scheme 2: Retrosynthetic strategy to
hydroxychloroquine.

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Metabolism
Hydroxychloroquine is N-dealkylated by CYP3A4 to the active metabolite
desethylhydroxychloroquine, as well as the inactive metabolites desethylchloroquine and
bidesethylchloroquine. Desethylhydroxychloroquine is the major metabolite. (Anonymus,
Hydroxychloroquine, 2020)
Favipiravir
Favipiravir, sold under the brand name Avigan or Abigan, is an antiviral medication used to treat
influenza in Japan. It is also being studied to treat a number of other viral infections. Like the
experimental antiviral drugs, it is a pyrazinecarboxamide derivative.
Chemistry
Favipiravir functions as a prodrug and undergoes ribosylation and phosphorylation intracellularly
to become the active favipiravir-RTP.7,10 Favipiravir-RTP binds to and inhibits RNA dependent
RNA polymerase (RdRp), which ultimately prevents viral transcription and replication.
Mechanismof action
The mechanism of action of favipiravir is novel compared to existing influenza antivirals that
primarily prevent entry and exit of the virus from cells. The active favipiravir-RTP selectively
inhibits RNA polymerase and prevents replication of the viral genome. There are several

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hypotheses as to how favipiravir-RTP interacts with RNA dependent RNA polymerase (RdRp).
Some studies have shown that when favipiravir-RTP is incorporated into a nascent RNA strand,
it prevents RNA strand elongation and viral proliferation. Studies have also found that the
presence of purine analogs can reduce favipiravir’s antiviral activity, suggesting competition
between favipiravir-RTP and purine nucleosides for RdRp binding.
Synthesis
Favipiravir was first synthesized from an inexpensive and commercially available starting
material, 2-aminopyrazine. The preferred route embedded within Scheme 4 consisted of seven
steps, and was highlighted by the novel and efficient synthesis of 3,6-dichloropyrazine-2-
carbonitrile 8.
Metabolism
Favipiravir is extensively metabolized with metabolites excreted mainly in the urine. The
antiviral undergoes hydroxylation primarily by aldehyde oxidase and to a lesser extent by
xanthine oxidase to the inactive metabolite, T705M1. (Anonymus, Favipiravir, 2020)
Azithromycin
Azithromycin is an antibiotic used for the treatment of a number of bacterial infections. This
includes middle ear infections, strep throat, pneumonia, traveler's diarrhea, and certain other
intestinal infections.

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Chemistry
Macrolides stop bacterial growth by inhibiting protein synthesis and translation, treating
bacterial infections 4. Azithromycin has additional immunomodulatory effects and has been used
in chronic respiratory inflammatory diseases for this purpose
Mechanismof action
In order to replicate, bacteria require a specific process of protein synthesis, enabled by
ribosomal proteins. Azithromycin binds to the 23S rRNA of the bacterial 50S ribosomal subunit.
It stops bacterial protein synthesis by inhibiting the transpeptidation/translocation step of protein
synthesis and by inhibiting the assembly of the 50S ribosomal subunit. This results in the control
of various bacterial infections. The strong affinity of macrolides, including azithromycin, for
bacterial ribosomes, is consistent with their broad‐ spectrum antibacterial activities.
Azithromycin is highly stable at a low pH, giving it a longer serum half-life and increasing its
concentrations in tissues compared to erythromycin
Synthesis
Azithromycin, which has improved pharmacological profiles compared with erythromycins, was
the target of an enantioselective synthesis. All the stereogenic quaternary carbon centers were
elaborated by a desymmetrization of 2‐ substituted glycerols using a chiral imine/CuCl2 catalyst.
Metabolism
In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed;
however, this drug is eliminated by the liver. (Anonymus, Azithromycin, 2020)
Ivermectin
Ivermectin is a medication used to treat many types of parasite infestations. This includes head
lice, scabies, river blindness, strongyloidiasis, trichuriasis, ascariasis, and lymphatic filariasis.

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Chemistry
Ivermectin is a semisynthetic, anthelminitic agent. It is an avermectin which a group of
pentacyclic sixteen-membered lactone (i.e. a macrocyclic lactone disaccharide) derived from the
soil bacterium Streptomyces avermitilis. Avermectins are potent anti-parasitic agents. Ivermectin
is the most common avermectin. It is a broad spectrum antiparasitic drug for oral administration.
It is sometimes used to treat human onchocerciasis (river blindness). It is the mixture of 22,23-
dihydro-avermectin B1a (at least 90%) and 22,23-dihydro-avermectin B1b (less than 10%).
Mechanismof action
Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in
invertebrate muscle and nerve cells of the microfilaria. This binding causes an increase in the
permeability of the cell membrane to chloride ions and results in hyperpolarization of the cell,
leading to paralysis and death of the parasite. Ivermectin also is believed to act as an agonist of
the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting GABA-mediated
central nervous system (CNS) neurosynaptic transmission. Ivermectin may also impair normal
intrauterine development of O. volvulus microfilariae and may inhibit their release from the uteri
of gravid female worms.
Synthesis
Ivermectin is obtained through selective, catalytic hydrogenation of the cis-22,23-double bond of
the avermectins B1a and B1b. The reaction is catalysed by the Wilkinson’s catalyst
chlorotris(triphenylphosphine)rhodium(I)[RhCl(PPh3)3]. The catalyst has to be removed after
the synthesis.
Metabolism
Ivermectin is metabolized in the liver, and ivermectin and/or its metabolites are excreted almost
exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose
excreted in the urine. The plasma half-life of ivermectin in man is approximately 18 hours
following oral administration.

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Dexamethasone
Dexamethasone is a type of corticosteroid medication. It is used in the treatment of many
conditions, including rheumatic problems, a number of skin diseases, severe allergies, asthma,
chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, and
along with antibiotics in tuberculosis.
Chemistry
Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and
promoting anti-inflammatory signals. Dexamethasone's duration of action varies depending on
the route. Corticosteroids have a wide therapeutic window as patients may require doses that are
multiples of what the body naturally produces. Patients taking corticosteroids should be
counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased
susceptibility to infections.
Mechanismof action
The short term effects of corticosteroids are decreased vasodilation and permeability of
capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids
binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple
downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and
demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid
derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote
anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-
inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids
for an extended period bind to the mineralocorticoid receptor, raising sodium levels and
decreasing potassium levels.
Synthesis
To synthesize dexamethasone, 16β-methylprednisolone acetate is dehydrated to the 9,11-dehydro
derivative. This is then reacted with a source of hypobromite, such as basic N-
bromosuccinimide, to form the 9α-bromo-11β-hydrin derivative, which is then ring-closed to an
epoxide.

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Metabolism
The metabolism of the synthetic glucocorticoid dexamethasone in human liver microsomal
incubations has been studied. ... Dexamethasone underwent side-chain cleavage to form 9 alpha-
F-AS. This metabolite was then a substrate for 6-hydroxylation. There was considerable
interindividual variability in metabolic profiles.
Chloroquine
Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria
remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases
typically require different or additional medication.
Chemistry
Chloroquine inhibits the action of heme polymerase, which causes the buildup of toxic heme in
Plasmodium species. It has a long duration of action as the half-life is 20-60 days. Patients
should be counselled regarding the risk of retinopathy with long term usage or high dosage,
muscle weakness, and toxicity in children.

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Mechanismof action
Chloroquine inhibits the action of heme polymerase in malarial trophozoites, preventing the
conversion of heme to hemazoin. Plasmodium species continue to accumulate toxic heme, killing
the parasite. Chloroquine passively diffuses through cell membranes and into endosomes,
lysosomes, and Golgi vesicles; where it becomes protonated, trapping the chloroquine in the
organelle and raising the surrounding pH. The raised pH in endosomes, prevent virus particles
from utilizing their activity for fusion and entry into the cell. Chloroquine does not affect the
level of ACE2 expression on cell surfaces, but inhibits terminal glycosylation of ACE2, the
receptor that SARS-CoV and SARS-CoV-2 target for cell entry. ACE2 that is not in the
glycosylated state may less efficiently interact with the SARS-CoV-2 spike protein, further
inhibiting viral entry.
Synthesis
Chloroquine, 7-chloro-4-(4-diethylamino-1-methylbutylamino)-quinoline (37.1. 3), is made by
reacting 4,7-dichloroquinoline (37.1. ... 1.4), which then undergoes high-temperature
heterocyclization to make the ethyl ester of 7-chloro-4-hydroxyquinolin-3-carboxylic acid.
Metabolism
Chloroquine is 60% bound to plasma proteins and equally cleared by the kidney and liver.
Following administration chloroquine is rapidly dealkylated via cytochrome P450 enzymes
(CYP) into the pharmacologically active desethylchloroquine and bisdesethylchloroquine.
Bibliography
Anonymus.(2020, June 20). Azithromycin.RetrievedfromDragBank:
https://www.drugbank.ca/drugs/DB00207
Anonymus.(2020, June 12). Favipiravir.RetrievedfromDrugbank:
https://www.drugbank.ca/drugs/DB12466
Anonymus.(2020, june 20). Hydroxychloroquine.RetrievedfromDrugbank:
https://www.drugbank.ca/drugs/DB01611

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