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IP International Journal of Comprehensive and Advanced Pharmacology 2020;5(2):49–57
Content available at: iponlinejournal.com
IP International Journal of Comprehensive and Advanced Pharmacology
Journal homepage: www.ipinnovative.com
Review Article
COVID-19: A pandemic declare by world health organization
Ashwini Arun Zanke1,*, Raju R Thenge1, Vaibhav S Adhao1
1Dr Rajendra Gode College Of Pharmacy, Malkapur, Maharashtra, India
ARTICLE INFO
Article history:
Received 04-05-2020
Accepted 14-05-2020
Available online 25-07-2020
Keywords:
Corona virus
COVID19
Fever
Pandemic
Respiratory
ABSTRACT
A novel coronavirus (SARS-CoV-2, currently known as 2019-nCoV) cause an acute respiratory disease
which is termed as the coronavirus disease 2019 (COVID-19) recently has spread firstly in China and
subsequently to other parts of world too and therefore, received worldwide attention. After the spread in
China, World Health Organization (WHO) on 30 January 2020 officially declared the COVID-19 epidemic
as a public health emergency of international concern. In the twenty-first century, firstly in 2002, the
emergence of SARS-CoV-2 resulted in the severe acute respiratory syndrome followed by the Middle East
respiratory syndrome coronavirus (MERS-CoV) in 2012, which was also remarked as the highly pathogenic
and large-scale epidemic coronavirus affected the human population. As per data released by WHO on 1
March 2020, globally a total of 87,137 cases and 79,968 cases in China were confirmed with 2977 deaths
(3.4%) worldwide. Subsequently, researchers have identified that SARS-CoV-2 belongs to
β
-coronavirus,
which is quite similar to genome which belongs to bat coronavirus, declaring bat as the natural host for
the particular virus. The novel coronavirus make use of the same receptor, angiotensin-converting enzyme
2 (ACE2) which was used by SARS-CoV, and chiefly spreads through the respiratory tract. Dominantly,
this COVID-19 virus shows evidence of sustained human-to-human transmission, across the globe. The
foremost clinical symptoms showing by most of the patients were fever, dry cough, fatigue, difficulty in
breathing and less commonly gastrointestinal infections. The older and persons with underlying diseases
like any cardiac problem, diabetes, cancer or kidney problems are more susceptible to COVID-19 infection
and also vulnerable to serious outcomes, which may be associated with acute respiratory distress syndrome
(ARDS) and cytokine storm. If we talk about the treatment part, currently, there are few specific antiviral
strategies, but several drug regimen and other antibody type investigations are under trial. The present
review summarizes the epidemiology, pathogenesis, and clinical characteristics of COVID-19 with the
current treatment procedures and future scientific advancements to combat the epidemic novel coronavirus.
© 2020 Published by Innovative Publication. This is an open access article under the CC BY-NC license
(https://creativecommons.org/licenses/by-nc/4.0/)
1. Introduction
1.1. What are coronaviruses?
Coronaviruses (CoVs) are a large family of viruses that
cause illness ranging from the common cold to more
severe diseases such as Middle East Respiratory Syndrome
(MERSCoV) and Severe Acute Respiratory Syndrome
(SARS-CoV). A novel coronavirus (nCoV) is a new strain
that has not been previously identified in humans.1
* Corresponding author.
E-mail address: ashwinizanke98@gmail.com (A. A. Zanke).
Coronaviruses are large, enveloped, positive-stranded
RNA viruses. They have the largest genome among all
RNA viruses. The genome is packed inside a helical capsid
formed by the nucleocapsid protein and further surrounded
by an envelope. Associated with the viral envelope are at
least three structural proteins: the membrane protein and the
envelope protein are involved in virus assembly, whereas the
spike protein mediates virus entry into host cells. Among the
structural proteins, the spike forms large protrusions from
the virus surface, giving coronaviruses the appearance of
having crowns (hence their name; corona in Latin means
crown). In addition to mediating virus entry, the spike is a
https://doi.org/10.18231/j.ijcaap.2020.012
2581-5555/© 2020 Innovative Publication, All rights reserved. 49
50 Zanke, Thenge and Adhao / IP International Journal of Comprehensive and Advanced Pharmacology 2020;5(2):49–57
critical determinant of viral host range and tissue tropism
and a major inducer of host immune responses. (Li, 2016)
Birds and mammlas commonly affected by coronaviruses
subsequently causing diversified fatal diseases. Generally
respiratory, gastrointestinal and central nervous system
will get affected by coronaviruses in humans and other
animals which are not only life threatening to human
but also causing economic loss. (Li, 2016) Coronaviruses
are efficient enough for adjusting to varied environments
through mutation and recombination with proficiency and
can affect new hosts and tissues with ease.
Rarely, certain coronaviruses can also affect certain
animal species and can generate new strains which can cross
over to human hosts and finally get transmitted between
humans. In past, humans had never been exposed to such
kind of viruses, therefore even vaccines are not available
not even humans have natural immunity for these. This is
the reason their mutations can swiftly lead to outbreak of
new kind of disease and eventually into pandemics. SARS
and MERS are the examples of such outbreaks.
Coronaviruses derived the specific termology from the
characteristic crown-like viral particles (virions) that present
on their surface like a dot.1–4 With the recent detection of
the 2019 novel coronavirus (COVID-19), there are now a
total of 7 coronaviruses known to infect humans.
1. Human coronavirus 229E (HCoV-229E
2. Human coronavirus OC43 (HCoV-OC43
3. Human coronavirus NL63 (HCoV-NL63
4. Human coronavirus HKU1
5. Severe acute respiratory syndrome-related coronavirus
(SARS-CoV
6. Middle East respiratory syndrome-related coronavirus
(MERS-CoV
7. Novel coronavirus (COVID-19, also known infor-
mally as Wuhan coronavirus)2
8. Novel coronavirus (COVID-19, also known infor-
mally as Wuhan coronavirus2
Prior to the global outbreak of SARS-CoV in 2003,
HCoV-229E and HCoV-OC43 were the only coronaviruses
known to infect humans. Following the SARS outbreak, 5
additional coronaviruses have been discovered in humans,
most recently the novel coronavirus COVID-19, believed to
have originated in Wuhan, Hubei Province, China. SARS-
CoV and MERSCoV are particularly pathogenic in humans
and are associated with high mortality. The present review
summarizes the epidemiology, pathogenesis, and clinical
characteristics of COVID-19 with the current treatment
procedures and future scientific advancements to combat the
epidemic novel coronavirus.
1.2. Origin and transmission of SARS-CoV-2
The SARS-CoV-2 is a
β
-coronavirus, which is enveloped
non-segmented positive-sense RNA virus (subgenus sar-
becovirus,Orthocoronavirinae subfamily) 3Coronaviruses
(CoV) are divided into four genera, including
α
−/
β
−/
γ
−/
δ
-CoV.
α
- and
β
-CoV are able to infect mammals,
while
γ
- and
δ
-CoV tend to infect birds. Previously, six
CoVs have been identified as human-susceptible virus,
among which
α
-CoVs HCoV-229E and HCoV-NL63,
and
β
-CoVs HCoV-HKU1 and HCoV-OC43 with low
pathogenicity, cause mild respiratory symptoms similar to a
common cold, respectively. The other two known
β
-CoVs,
SARS-CoV and MERS-CoV lead to severe and potentially
fatal respiratory tract infections5was found that the genome
sequence of SARS-CoV-2 is 96.2% identical to a bat CoV
RaTG13, whereas it shares 79.5% identity to SARS-CoV.
Based on virus genome sequencing results and evolutionary
analysis, bat has been suspected as natural host of virus
origin, and SARSCoV-2 might be transmitted from bats via
unknown intermediate hosts to infect humans. It is clear
now that SARS-CoV-2 could use angiotensin-converting
enzyme 2 (ACE2), the same receptor as SARS-CoV6to
infect humans.
1.3. How is SARS-CoV-2 coronavirus transmitted?7
a. The transmission of SARS-CoV-2 occurs by the following
mechanisms:
Commonly spread through close contacts between two
persons (about less than 6 feet/1 8 metres
b. Other prevalent reason for person-to-person spread
is primarily via respiratory droplets produced when an
infected person coughs or sneezes, which is similar to the
spread of influenza and other respiratory pathogens.
c. Respiratory droplets further can go inside the mouth,
noses or eyes of people who came in contact with the
infected person or in serious transmission can be inhaled
into the lungs.
d. Even by touching the surface or any object where the
virus reside can be the source of infection of COVID-19 and
get transmitted to the person by touching and further reaches
to their facial part. But this is not the primary way of virus
transmission (Centres for Disease Control and Prevention,
2020). Infact it is evident that coronaviruses can remain
live on inanimate surfaces for several hours or even days.
(Kampf G, 2020).
e. In cases of most respiratory viruses, the most
symptomatic one is supposed to be most contagious. But
COVID-19 reports have suggested even the spread occurs
from an asymptomatic infected person to any close contact.
(Centres for Disease Control and Prevention, 2020) (Rothe,
2020).8Ongoing researches suggest that asymptomatic (or
pre-symptomatic) patients not only transmits the COVID-
19 infection but also the expansion of the disease is really
fast (Ruiyun Li, 2020).9
f. With 10- 14 days of long incubation period and
even after the remission of symptoms patients can remain
contagious for one to two weeks. According to research
Zanke, Thenge and Adhao / IP International Journal of Comprehensive and Advanced Pharmacology 2020;5(2):49–57 51
done by W¨
olfel et al, symptoms only remains for the first
week but even though viral RNA can be detectable in throat
swabs for upto second week. Stool and sputum samples
remained RNA positive for longer periods. (Roman W ¨
olfel,
2020)10
g. Information regarding COVID-19 affect during preg-
nancy is minutest and intrauterine or perinatal transmission
has not been identified till now. There are reports of 18
pregnant women with COVID-19 infection with neonates
have no presence of the virus. However, two neonatal
cases of infection have been documented with COVID-19
positive mother. In one case, the diagnosis was made at
day 17 of life after close contact with the infant’s mother
and a maternity matron who were both infected with the
virus. The other case was diagnosed 36 hours after birth;
the source and time of transmission in that case were
unclear. (McIntosh, Coronavirus disease 2019 (COVID-
19) - Special situation: Pregnant women, 2020). Several
developed countries suggested about pregnant women to
remain isolated as preventive measures because there is
increased risk of infection.11,12
h. Althogh sparse data suggest that in coronovirus
infected mothers, the virus has not been detected in their
breast milk. As we all know breast milk provides immunity
and protection against many diseases to the neonates but
there is no assurance about mothers with COVID-19 can
transmit the virus via breast milk.
i. The CDC has no specific guidelines for continuing the
breastfeeding during infection of mothers with any type of
coronaviruses including with SARS-CoV or Middle Eastern
Respiratory Syndrome (MERS-CoV) or even COVID19.
CDC recommends proper precautions should be taken
during breastfeeding to avoid any kind of transmission of
infection to the neonate. WHO highlights the less chances
of transmission of respiratory viruses through breast milk,
and currently suggest that mothers with COVID-19 can
breastfeed. (Academy of Breastfeeding Medicine, 2020)
1.4. Epidemiology −reservoirs and transmission
The current epidemic of acute respiratory tract infection
of unknown origin spread out initially in Wuhan, China,
since early December 2019, which later suggest its relation
to a seafood market. Further research concluded that bat
can be the potential reservoir of SARS-CoV-2.13,14 Till
now, the origin of SARS-CoV-2 from the seafood is not
established evidentially. Preferably, the fact that bats are
the natural reservoir of a wide variety of CoVs, including
SARS-CoV-like and MERS CoV-like viruses is far better
accepted.15,16 Upon virus genome sequencing, the COVID-
19 was analyzed throughout the genome to Bat CoV
RaTG13 and showed 96.2% overall genome sequence
identity5suggesting that bat CoV and human SARS-CoV-
2 might share the same ancestor, although bats are not
available for sale in this seafood market17 Besides, protein
sequences alignment and phylogenetic analysis18 showed
that similar residues of receptor were observed in many
species, which provided more possibility of alternative
intermediate hosts, such as turtles, pangolin and snacks.
Human-to-human transmission of COVID-19 mainly occurs
due to close contact with the patients or incubation
carriers. A report declares that19 31.3% of patients were
the ones who recently visited Wuhan and 72.3% of
patients contacting with people from Wuhan among affected
nonresidents of Wuhan. National Health Commission of
China declares that COVID-19 transmission occurred in
3.8% healthcare workers. In contrast, the transmission
of SARS-CoV and MERS-CoV was reported to occur
primarily through nosocomial transmission. Infections
of healthcare workers in 33–42% of SARS cases and
transmission between patients (62–79%) was the most
common route of infection in MERS-CoV cases.20,21 Direct
contact with intermediate host animals or consumption
of wild animals was suspected to be the main route of
SARS-CoV-2 transmission. However, the source(s) and
transmission routine(s) of SARS-CoV-2 remain elusive.
Fig. 1: Epidemic pheses
Four transmission scenarios are observed.
Fig. 2: Epidemic phase
1. Four transmission scenarios are observed.
2. Countries with no cases (no cases)
1. Four transmission scenarios are observed.
2. Countries with no cases (no cases)
3. Countries with one or more cases imported or locally
acquired (sporadic cases)
1. Four transmission scenarios are observed.
2. Countries with no cases (no cases)
52 Zanke, Thenge and Adhao / IP International Journal of Comprehensive and Advanced Pharmacology 2020;5(2):49–57
Fig. 3: Epidemic phases
Fig. 4: Epidemic phases
3. Countries with one or more cases imported or locally
acquired (sporadic cases)
4. Countries experiencing clusters of casas in time
geographic location or common exposure (clusters of
cases)
Fig. 5: Epidemic phases
1. Four transmission scenarios are observed.
2. Countries with no cases (no cases)
3. Countries with one or more cases imported or locally
acquired (sporadic cases)
4. Countries experiencing clusters of casas in time
geographic location or common exposure (clusters of
cases)
5. Countries experiencing larger outbreaks of local
transmission (community transmission).
1. Set up screening and triage
2. Set up COVID 19 designated wards in health facilities.
•Set up screening and triage
•Set up COVID 19 designated wards in health facilities.
•COVID-19 designated treatment area
•Repurpose existing buildings
•Community facilities.
Fig. 6: Epidemic phase
Fig. 7:
Fig. 8:
Zanke, Thenge and Adhao / IP International Journal of Comprehensive and Advanced Pharmacology 2020;5(2):49–57 53
Fig. 9: Epidemic area
Fig. 10: Epidemic phases
1. Set up screening and triage
2. Set up COVID 19 designated wards in health facilities.
3. COVID-19 designated treatment area
4. Repurpose existing buildings
5. Community facilities.
6. New covid 19 facilities.
1.5. Clinical symptoms
A recent study led by Prof. Nan-Shan Zhong’s team, by
sampling 1099 laboratory-confirmed cases, found that the
common clinical manifestations included.
fever (88.7%), sputum production (33.4%),cough
(67.8%)shortness of breath, (18.6%), fatigue(38.1%), sore
throat(13.6%), headached17 In addition, a part of patients
manifested gastrointestinal symptoms, with diarrhoea
(3.8%) and vomiting (5.0%). The clinical manifestations
were in consistence with the previous data of 41, 99, and 138
patients analysis in Hubei province.22–24 Fever and cough
were the dominant symptoms whereas upper respiratory
symptoms and gastrointestinal symptoms were rare,
suggesting the differences in viral tropism as compared
with SARS-CoV.25 MERSCoV.26 and influenza. 27
The elderly and those with underlying disorders (i.e.,
hypertension, chronic obstructive pulmonary disease,
diabetes, cardiovascular disease), developed rapidly into
acute respiratory distress syndrome, septic shock, metabolic
acidosis hard to correct and coagulation dysfunction, even
leading to the death.28 In laboratory examination results,
most patients had normal or decreased white blood cell
counts, and lymphocytopenia19,29 But in the severe patients,
the neutrophil count, D-dimer, blood urea, and creatinine
levels were higher significantly, and the lymphocyte
counts continued to decrease. Additionally, inflammatory
factors (interleukin (IL)-6, IL-10, tumournecrosis factor-
α
(TNF-
α
) increase, indicating the immune status of patients.
The data showed that ICU patients had higher plasma
levels of IL-2, IL-7, IL-10, granulocyte colony-stimulating
factor (GCSF), 10 kD interferongamma-induced protein
(IP-10), monocyte chemoattractant protein-1 (MCP-
1), macrophage inflammatory protein 1-
α
(MIP-1
α
), and
TNF-
α
.28 Moreover, the CT imaging showed that computed
tomography on the chest was ground-glass opacity (56.4%)
and bilateral patchy shadowing (51.8%),19 sometimes with
a rounded morphology and a peripheral lung distribution,
analyzed from the patients in the Fifth Affiliated Hospital,
Sun Yat-Sen University.30 Clinicians have been aware that,
a part of confirmed patients appeared the normal CT image
presentations. The diagnostic sensitivity of radiologic is
limited, so it is necessary to verify with clinical symptoms
and virus RNA detections.
2. Treatment of COVID-19
Current therapies Given the lack of effective antiviral
therapy against COVID-19, current treatments mainly
focused on symptomatic and respiratory support according
to the Diagnosis and Treatment of Pneumonia Caused by
COVID-19. issued by National Health Commission of the
People’s Republic of China.31 Nearly all patients accepted
oxygen therapy, and WHO recommended extracorporeal
membrane oxygenation (ECMO) to patients with refractory
hypoxemia.32 Rescue treatment with convalescent plasma
and immunoglobulin G33 are delivered to some critical
cases according to their conditions.Antiviral treatments
Based on the experience of fighting the epidemic
SARSCoV and MERS-CoV previously, we may learn
some lessons for some treatment strategies against
coronavirus.34 Antiviral drugs and systemic corticosteroid
treatment commonly used in clinical practice previously,
including neuraminidase inhibitors (oseltamivir, peramivir,
zanamivir, etc), ganciclovir, acyclovir, andribavirin,as well
as methylprednisolone.3,22for influenza virus, are invalid
for COVID-19 and not recommendedRemdesivir (GS-
5734) is a 1′-cyano-substituted adenosine nucleotide analog
prodrug and shows broadspectrum antiviral activity against
several RNA viruses. Based on the data collected from in
vitro cell line and mouse model, remdesivir could interfere
with the NSP12 polymerase even in the setting of intact
Exon proofreading activity.35 Remdesivir has been reported
54 Zanke, Thenge and Adhao / IP International Journal of Comprehensive and Advanced Pharmacology 2020;5(2):49–57
to treat the first US case of COVID-19 successfully.36
Chloroquine is a repurposed drug with great potential to
treat COVID-19. Chloroquine has been used to treat malaria
for many years.36 with a mechanism that is not well
understood against some viral infections. Several possible
mechanisms are investigated: Chloroquine can inhibit pH-
The other antiviral drugs include nitazoxanide, favipiravir,
nafamostat (See Table 1 for details).
dependent steps of the replication of several viruses,37
with a potent effect on SARS-CoV infection and spread.4
Moreover, chloroquine has immunomodulatory effects,
suppressing the production/release of TNF-
α
and IL-6.
It also works as a novel class of autophagy inhibitor,38
which may interfere with viral infection and replication.
Several studies have found that chloroquine interfered with
the glycosylation of cellular receptors of SARS-CoV39 and
functioned at both entry and at post-entry stages of the
COVID-19 infection in Vero E6 cells.40 A combination of
remdesivir and chloroquine was proven to effectively inhibit
the recently emerged SARS-CoV-2 in vitro. Scientists
previously confirmed that the protease inhibitors lopinavir
and ritonavir, used to treat infection with human immun-
odeficiency virus (HIV),41 could improve the outcome of
MERS-CoV42 and SARSCoV43 patients. It has reported
that
β
-coronavirus viral loads of a COVID-19 patient
in Korea significantly decreased after lopinavir/ritonavir
(Kaletra®, AbbVie, North Chicago, IL, USA) treatment.44
Additionally, clinicians combined Chinese and Western
medicine treatment including lopinavir/ritonavir (Kaletra),
arbidol, and Shufeng Jiedu Capsule (SFJDC, a traditional
Chinese medicine) and gained significant improvement in
pneumonia associated symptoms in Shanghai Public Health
Clinical Center, China.45
Originating from reservoir of bats and unknown
intermediate hosts, SARS-CoV-2 binds to ACE2 with high
affinity as a virus receptor to infect humans. Secondly, the
susceptible population involves the elderly and people with
certain underlying medical conditions, which requires more
attention and care. Thirdly, so far, the supporting treatments,
combined with potent antiviral drugs, such as remdesivir,
chloroquine, or lopinavir/ritonavir, have been conducted
with definite effect on treat COVID-19 patients,while
solid data from more clinical trials are needed. However,
questions remain vague and more studies are urgent to
explore the transmission and pathogenicity mechanism of
the emerging coronavirus. To make clear the evolutionary
path from the original host to cross-species transmission
so as to potentially limit the transmission to animals
or humans. In addition, to uncover the mystery of the
molecular mechanism of viral entry and replication, which
provides the basis of future research on developing targeted
antiviral drugs and vaccines? Given more than 80% of
patients are confirmed in Hubei province, the hospitals and
medical workers in Hubei are facing and bearing enormous
pressure and severe challenge, including a high risk of
infection and
adequate protection, as well as overwork, frustration
and exhaustion 61Chinese Government and authorities have
launched psychological intervention, and we sincerely hope
that Chinese people and other countries overcome the
epidemic as fast as possible.
3. Convalescent plasma therapy
For COVID-19 patients with rapid disease progression,
severe and critical illness, convalescent plasma therapy
(CPT) can be tried (National Health Commission of the
People’s Republic of China, 2020). CPT utilises a certain
titre of virus-specific antibodies in the plasma of the
convalescent individual to enable the patient receiving
the infusion to obtain passive immunity and remove
pathogens from the blood circulation. This method has been
successfully used in the treatment of SARS and H1N1
influenza, and is an effective treatment (Chen L, 2020).46
The use of CPT treatment can follow the following
principles (National Health Commission of the People’s
Republic of China, 2020)
1. In principle, the course of disease does not exceed
three weeks. Also, the patient should have a positive
viral nucleic acid test or viraemia certified by clinical
experts.
2. Patients with severe disease with rapid disease
progression, or critically ill early stage patients, or
patients comprehensively evaluated by clinical experts
as requiring plasma therapy. The infusion dose is
determined according to the clinical situation and the
weight of the patient, usually the infusion dose is
200500 ml (4-5 ml/kg).
3. Before, during, and after the infusion, detailed
records and clinical observation should be made to
assess the adverse effects of plasma infusion. The
main types of adverse transfusion reactions include
transfusion-related circulation overload, transfusion-
related acute lung injury, transfusion-related dyspnoea,
allergic reactions, transfusion-associated hypoten-
sion reactions, non-haemolytic febrile reactions,
acute haemolytic transfusion reactions, and delayed
haemolytic transfusion reaction, infectious transfusion
reaction, other/unknown, etc.
4. Advances in vaccines development for the treatment
of COVID-19
Since the vaccine development process involves procedures
such as virus strain isolation and selection, in vitro
experiments, animal experiments, clinical trials, and
administrative approvals, it takes a long time. At present,
some recognition sites for SARS-CoV-2 have been found
and can be used for vaccine development (Ahmed SF, 2020)
Zanke, Thenge and Adhao / IP International Journal of Comprehensive and Advanced Pharmacology 2020;5(2):49–57 55
Table 1: Common and potent antiviral drugs
Status Drugs Action mode Anti-infective mechanism Target diseases Ref.
Approved Lopinavir/
Ritonavir
Protease
inhibitors
Inhibiting HIV-1 protease for protein
cleavage, resulting in non-infectious,
immature viral particle
HIV/AIDS, SARS,
MERS
41–43
Approved,
Investigational,
Vet approved
Chloroquine 9-
aminoquinolin
Increasing endosomal pH,
immunomodulating, autophagy
inhibitors
Malaria,
autoimmune disease
37-40
Experimental Remdesivir
(GS-5734)
Nucleotide
analogue
prodrug
Interfering with virus post-entry Ebola, SARS,
MERS
46-47-48
Investigationa Nafamostat Synthetic
serine
protease
inhibitor
Prevents membrane fusion by
reducing the release of cathepsin B;
anticoagulant activities
Influenza, MERS,
Ebola
49-50
Approved Ribavirin Synthetic
guanosine
nucleoside
Interfering with the synthesis of viral
mRNA (a broad-spectrum activity
against several RNA and DNA
viruses)
HCV, SARS,
MERS
51-52
Approved Oseltamivir Neuraminidase
inhibitor
Inhibiting the activity of the viral
neuraminidase enzyme, preventing
budding from the host cell,
Influenza viruses A 53-54
Approved Penciclovir/
Acyclovir
Nucleoside
analog
A synthetic acyclic guanine
derivative, resulting in chain
termination HSV, VZ
HSV, VZ 55
Approved,
Investigational
Ganciclovir
Nucleoside
analog
Nucleoside
analog
Potent inhibitor of the Herpesvirus
family including cytomegalovirus
AIDS-associated
cytomegalovirus
infections
56
Investigational Favipiravir
(T-705
Nucleoside
analog
Viral RNA polymerase inhibitor
Acting on viral genetic copying to
prevent its reproduction, without
affecting host cellular RNA or DNA
synthesis
Ebola, influenza
A(H1N1)
57-58
Approved,
Investigational,
Vet approved
Nitazoxanide
Antiprotozoal
agent
Antiprotozoal
agent
Modulating the survival, growth, and
proliferation of a range of
extracellular and intracellular
protozoa, helminths, anaerobic and
microaerophilic bacteria, viruses
A wide range of
viruses including
human/animal
coronaviruses
59-60
(Ramaiah A, 2020).63−64
The Ministry of Science and Technology of the
People’s Republic of China has organised national key
units to carry out joint research, and arranged five
technical routes in parallel, including inactivated vaccines,
recombinant genetically engineered vaccines, adenovirus
vector vaccines, nucleic acid vaccines (mRNA vaccine and
DNA vaccine), and vaccines made from attenuated influenza
viral vaccine vectors.
5. Progress of clinical trials for the treatment of
COVID-19
At present, clinical research projects on new coronavirus
pneumonia drugs are ongoing. As of 9 am on 8 March
2020, a total of 436 clinical trials were retrieved from the
Chinese Clinical Trials Registry, and a total of 181 clinical
trials involving drug treatment were screened out, of which
107 were randomised controlled trials, four were real-world
studies, and 70 were non-randomised controlled trials.Of
the 181 studies, 176 were initiated by Chinese research
institutions, mainly distributed in Hubei (43), Shanghai
(25), Beijing (20), Zhejiang (20) and Guangdong (19). The
remaining five studies were initiated by other countries.
The drugs involved in clinical trials mainly include
traditional Chinese medicine (TCM) interventions (64
items), antiviral drugs (40 items), immunotherapy drugs
(28 items, such as Interferon, Thymosin, Immunoglobulin,
PD1 inhibitors, etc.), anti-malaria drugs (21 items, such as
chloroquine, hydroxychloroquine, chloroquine phosphate),
glucocorticoids (6 items), and other drugs (22 items, such as
vitamin C, vitamin D, polymyocyte injection, zinc sulphate,
acetylcysteine, etc.).
The most clinical trials of antiviral medicines
are anti-HIV medicines (14 items, such as
lopinavir/ritonavir,darunavir/cobistastat, azivudine),
followed by anti-influenza viruses medicines (13, such as
umifenovir, fapilavir), and five clinical trials of remdesivir,
56 Zanke, Thenge and Adhao / IP International Journal of Comprehensive and Advanced Pharmacology 2020;5(2):49–57
which are considered to have potential efficacy against
COVID-19.
6. Prevention
To help control further spread of the virus, people who
are suspected or confirmed to have the disease should be
isolated from other patients and treated by health workers
using strict infection control precautions.
1. People who have had social contact with symptomatic
individuals with confirmed COVID19 should be
followed up as a contact through the local healthcare
teams
2. WHO’s standard recommendations for the general
public to reduce exposure to and transmission of this
and other respiratory illnesses are as follows, which
include hand and respiratory hygiene, and safe food
practices.65−66
3. Frequently clean hands by using alcohol-based hand
rub or soap and water
4. When coughing and sneezing cover the mouth and
nose with a flexed elbow or tissue – throw the tissue
away immediately and wash hands.
5. Avoid close contact with anyone who has fever and
cough
6. If you have fever, cough and difficulty breathing seek
medical care early and share previous travel history
with your healthcare provider.
7. When visiting live markets in areas currently
experiencing cases of novel coronavirus, avoid direct
unprotected contact with live animals and surfaces in
contact with animals.
8. The consumption of raw or undercooked animal
products should be avoided. Raw meat, milk or
animal organs should be handled with care, to avoid
crosscontamination with uncooked foods, as per good
food safety practices. (World Health Organization,
2020).
7. Source of Funding
None.
8. Conflict of Interest
None.
References
1. Li F. Structure, Function, and Evolution of Coronavirus Spike
Proteins. Ann Rev Virol. 2016;3(1):237–61.
2. Riou J, Althaus CL. Pattern of early human-to-human transmission
of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to
January 2020. Euro Surveill. 2020;25(4):2000058.
3. Zumla A, Chan JFW, Azhar EI, Hui DSC, Yuen KY. Coronaviruses
— drug discovery and therapeutic options. Nat Rev Drug Discov.
2016;15(5):327–47.
4. Aguiar ACC, Murce E, Cortopassi WA, Pimentel AS, Almeida
MMFS, Barros DCS, et al. Chloroquine analogs as antimalarial
candidates with potent in vitro and in vivo activity. Int J Parasitol
Drugs Drug Resist. 2018;8(3):459–64.
5. Yin Y. Whttps://doi.org/10.2807/1560-7917.ES.2020.25.4. 2000058;.
6. Zhu N, Zhang D, Mers RG. SARS and other coronaviruses as causes
of pneumonia. Respirol. 2018;23(2):130–7.
7. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A
pneumonia outbreak associated with a new coronavirus of probable
bat origin. Nat. 2020;.
8. Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of
coronaviruses on inanimate surfaces and their inactivation with
biocidal agents. J Hosp Infect. 2020;104(3):246–51.
9. Rothe C. Transmission of 2019-nCoV Infection from an
Asymptomatic Contact in Germany. N Eng J Med - Correspondence.
2020;.
10. Li R, P S. Substantial undocumented infection facilitates the rapid
dissemination of novel coronavirus (SARS-CoV2). Sci. 2020;.
11. W¨
olfel R, M V. Clinical presentation and virological assessment of
hospitalized cases of coronavirus disease 2019 in a travel-associated
transmission cluster; 2020. Available from: https://www.medrxiv.org/
content/10.1101/2020.03.05.20030502v1.full.pdf.
12. Mcintosh K. Retrieved from UpToDate Coronavirus disease 2019
(COVID-19; 2020. Available from: https://www.uptodate.com/
contents/coronavirus-disease-2019-covid-19.
13. Mcintosh K. Coronavirus disease 2019 (COVID-19) - Special
situation: Pregnant women. (M. S. Hirsch, Editor) Retrieved from
UpToDate. 2020;.
14. Giovanetti M, Benvenuto D, Angeletti S, Ciccozzi M. The first two
cases of 2019-nCoV in Italy: Where they come from? J Med Virol.
2020;p. 1–4.
15. Paraskevis D, Kostaki EG, Magiorkinis G, Panayiotakopoulos G,
Sourvinos G, Tsiodras S. Full-genome evolutionary analysis of the
novel corona virus (2019-nCoV) rejects the hypothesis of emergence
as a result of a recent recombination event. Infect Genet Evol.
2020;79:10421.
16. Hampton T. Bats may be SARS reservoir. JAMA. 2005;294(18):2291–
2291.
17. Li W, Shi Z, Yu M, Ren W, Smith C, Epstein JH, et al. Bats are natural
reservoirs of SARS-like coronaviruses. Science. 2005;310(5748):676–
9.
18. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new
coronavirus associated with human respiratory disease in China. Nat.
2020;Available from: https://doi.org/10.1038/s41586-020- 2008-3.
19. Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H, et al. Composition and
divergence of coronavirus spike proteins and host ACE2 receptors
predict potential intermediate hosts of SARS-CoV-2. J Med Virol.
2020;Available from: https://doi.org/10.1002/jmv.25726.
20. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical
characteristics of coronavirus disease 2019 in China. N Engl J Med.
2020;.
21. Chowell G, Abdirizak F, Lee S, Lee J, Jung E, Nishiura H, et al.
Transmission characteristics of MERS and SARS in the healthcare
setting: a comparative study. BMC Med. 2015;13(1):210.
22. Kang CK, Song KH, Choe PG, Park WB, Bang JH, Kim ES, et al.
Clinical and epidemiologic characteristics of spreaders of middle east
respiratory syndrome coronavirus during the 2015 outbreak in Korea.
J Korean Med Sci. 2017;32(5):744–9.
23. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al.
Clinical characteristics of 138 hospitalized patients with 2019 novel
coronavirus-infected pneumonia in Wuhan. JAMA. 2020;Available
from: https://doi.org/10.1001/jama.2020.1585.
24. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features
of patients infected with 2019 novel coronavirus in Wuhan China. .
Lancet. 2020;395:497–506.
25. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al.
Epidemiological and clinical characteristics of 99 cases of 2019 novel
coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet.
2020;395:507–520.
Zanke, Thenge and Adhao / IP International Journal of Comprehensive and Advanced Pharmacology 2020;5(2):49–57 57
26. N L, D H, A W, P C, P C, GM J, et al. A Major Outbreak of
Severe Acute Respiratory Syndrome in Hong Kong. N Engl J Med.
2003;348(20):1986–94.
27. Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar
S, Al-Barrak A, et al. Epidemiological, demographic, and clinical
characteristics of 47 cases of Middle East respiratory syndrome
coronavirus disease from Saudi Arabia: a descriptive study. Lancet
Infect Dis. 2013;13(9):752–61.
28. Tchesnokov E, Feng J, Porter D, G ¨
otte M. Mechanism of Inhibition
of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir.
Viruses. 2019;11(4):326.
29. Wang H, Xiao X, Lu J, Chen Z, Li K, Liu H, et al. Factors associated
with clinical outcome in 25 patients with avian influenza a (H7N9)
infection in Guangzhou, China. BMC Infect Dis. 2016;16(1):534.
30. Kui L, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, et al. Clinical
characteristics of novel coronavirus cases in tertiary hospitals in Hubei
Province. Chin Med J. 2020;.
31. Chung M, Bernheim A, Mei X, Zhang N, Huang M, Zeng X, et al. CT
imaging features of 2019 novel coronavirus (2019-nCoV). Radiol.
2020;.
32. National Health Commission of the People’s Republic of China.
Diagnosis and Treatment of Pneumonia Caused by 2019-nCoV
(version 6); 2020. Available from: http://www.gov.cn/zhengce/
zhengceku/2020-02/19/content 5480948.htm.Accessed.
33. Clinical management of severe acute respiratory infection when
novel coronavirus (nCoV) infection is suspected; 2020. Available
from: https://www.who.int/publicationsdetail/clinical-management-
of-severe-acute- respiratory-infection- when-novelcoronavirus-(ncov)
-infection- is-suspected.Accessed28.
34. Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential
therapy for COVID-19. Lancet Infect Dis. 2020;20(4):398–400.
35. Li H, Wang YM, Xu JY, Cao B. Potential antiviral therapeutics for
2019 Novel Coronavirus. Chin J Tuberc Respir Dis. 2020;43(0):E002.
36. Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu
X, et al. Coronavirus susceptibility to the antiviral remdesivir (gs-
5734) is mediated by the viral polymerase and the proofreading
exoribonuclease. mBio. 2018;9(2):e00221–18.
37. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H,
et al. First Case of 2019 Novel Coronavirus in the United States. N
Engl J Med. 2020;382(10):929–36.
38. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE,
Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS
coronavirus infection and spread. Virol J. 2005;2:69.
39. Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of
chloroquine on viral infections: an old drug against today’s diseases.
Lancet Infect Dis. 2003;3(11):722–7.
40. Golden EB, Cho HY, Hofman FM, Louie SG, Sch¨
onthal AH, Chen
TC, et al. Quinoline-based antimalarial drugs: a novel class of
autophagy inhibitors. Neurosurg Focus. 2015;38(3):E12.
41. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and
chloroquine effectively inhibit the recently emerged novel coronavirus
(2019-nCoV) in vitro. Cell Res. 2020;.
42. Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the
management of HIV infection. Drugs. 2003;63(8):769–802.
43. Arabi YM, Asiri AY, Assiri AM, Jokhdar HAA, Alothman A, Balkhy
HH, et al. Treatment of Middle East respiratory syndrome with
a combination of lopinavir/ritonavir and interferon-
β
1b (MIRACLE
trial): statistical analysis plan for a recursive two-stage group
sequential randomized controlled trial. Trials. 2020;21(1):8.
44. Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, et al.
Role of lopinavir/ritonavir in the treatment of SARS: initial virological
and clinical findings. Thorax. 2004;59(3):252–6.
45. Lim J, Jeon S, Shin HY, Kim MJ, Seong YM, Lee WJ, et al. Case of the
index patient who caused tertiary transmission of COVID-19 infection
in Korea: the application of lopinavir/ritonavir for the treatment of
COVID-19 infected pneumonia monitored by quantitative RT-PCR. J
Korean Med Sci. 2020;35(6):e79.
46. Kang L, Li Y, Hu S, Chen M, Yang C, Yang BX, et al. The mental
health of medical workers in Wuhan, China dealing with the 2019
novel coronavirus. Lancet Psychiatry. 2020;7(3):e14.
Author biography
Ashwini Arun Zanke M.Pharma (Pharmaceutics)
Raju R Thenge Assistant Professor
Vaibhav S Adhao Assistant Professor
Cite this article: Zanke AA, Thenge RR, Adhao VS. COVID-19: A
pandemic declare by world health organization.IP Int J
Comprehensive Adv Pharmacol 2020;5(2):49-57.
