Sri Chaitanya Educational Institutions, India.

COVID-19

HONOUR THE HEROES:

DOCTORS, NURSES AND OTHER FRONTLINE WORKERS, MANY OF WHOM HAVE GIVEN
THEIR LIVES.

DO YOUR PART.
WEAR A MASK.

Student Name: Krithik

Class: 12
Group: PCMB
Subject: Biology
 Acknowledgement
It gives me a great sense of pleasure to present the report of the Project Work
undertaken during my final year of higher secondary education, class XII. I would like to
express my gratitude and appreciation to all those who gave me the possibility to complete
this project. Special thanks is to my Zoology lecturer Mr. Chandra Sekhar V. S., and my
Botany lecturer Mr. Lingareddy Immareddy, whose guidance, knowledge and absolute
support helped me in all time of fabricating this document.
My deepest thanks to my College Principal, Mr. Prasad, and my Biology Teacher, Ms.
Santhi C.H, for granting me the golden opportunity to do this fantastic project.
It would be my privilege to extend my special thanks of gratitude with much
appreciation to my uncle, Dr. M. Karthikeyan, my aunt, Dr. Usha Devi, my elder cousin,
Dr. Vignesh K., and my parents for their crucial guidance and encouragement in achieving
the goal as well as to maintain the coherency, and by extension, the progress, in track. I also
sincerely thank them for the time spent in proofreading this project.
I would also like to thank CBSE for providing such innovative projects and wonderful
platform. This project has enlightened me in understanding the structure of the virus and
the principles of the mechanism the virus’ attack.
Last but not the least, my profound thanks go to all my friends, for spending their time
in the contribution and overall development of this project.

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 Table of Contents
Acknowledgement ........................................................................................... 2
COVID-19: An Overview ..................................................................................... 4
Quantitative treatment by means of biotechnology .......................................... 5
Elementary structure .................................................................................................................................................. 5
Crystal Structure of COVID-19 MPro ........................................................................................................................ 8
E-Protein ion channel activity ................................................................................................................................... 9
The Mechanism of Attack ........................................................................................................................................ 10

Qualitative treatment ...................................................................................... 11

Diagnosis.................................................................................................................................................................... 11
Symptoms .................................................................................................................................................................. 12
Treatment ................................................................................................................................................................... 13
Preventions ................................................................................................................................................................ 13
Vaccination ................................................................................................................................................................ 14

Effect of COVID-19 on Cancer Patients ............................................................ 15

The risk ....................................................................................................................................................................... 15
Safety in people with cancer .................................................................................................................................. 15

Protection against the virus ............................................................................. 16

Vaccine development .............................................................................................................................................. 16
Trial test of the FDA-approved drugs for COVID-19 patients .......................................................................... 17

India’s role in biotechnology in the fight against the COVID-19 Pandemic ....... 21
Response to the COVID-19 Pandemic ............................................................... 25
Conclusion ...................................................................................................... 28
Bibliography .................................................................................................... 29

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 COVID-19: An Overview
COVID-19 is the disease caused by SARS-CoV-2, the coronavirus that emerged in December
2019. This disease can cause mild to severe respiratory illness, including death. A coronavirus is a
kind of common virus that causes an infection in your nose, sinuses, or upper throat.
Coronaviruses are a group of related RNA viruses. They are called “corona” because of crown-
like spikes on the surface of the virus. It should be mentioned that SARS-CoV-2 is responsible for
the 3rd respiratory syndrome, caused by coronaviruses during last two decades, while SARS-CoV
and Middle East Respiratory Syndrome coronavirus (MERS-CoV) were both connected to the
development of severe respiratory syndromes in 2003 and 2012, respectively.

Fig: A SARS-CoV-2 virus

In early 2020, after a December 2019 outbreak in China, the World Health Organization identified
SARS-CoV-2 as a new type of coronavirus (Covid-19). The outbreak quickly spread around the
world (pandemic). It spreads the same way other corona viruses do, mainly through person-top-
person contact. Infections range from mild to deadly. Most of the time, it spreads when a sick
person coughs or sneezes. They can spray droplets as far as 6 feet away.
SARS-CoV-2 may have originated in an animal and changed (mutated) so it could cause illness in
humans. In the past, several infectious disease outbreaks have been traced to viruses originating in
birds, pigs, bats and other animals that mutated to become dangerous to humans.
The Coronavirus must infect living cells in order to reproduce. Inside the virus, genetic material
contains the information to make more copies of itself. A protein shell provides a hard protective
enclosure for the genetic material as the virus travels between the people it infects. An outer
envelope allows the virus to infect cells by merging with the cell’s outer membrane. Projecting
from the envelope are spikes of protein molecules. Both a typical influenza virus and the new
corona virus use their spikes like a key to get inside a cell in one’s body, where it takes over the
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cell’s internal machinery, repurposing it to build the components of new viruses. When an infected
person talks, coughs or sneezes, droplets carrying the virus may land in a non-infected person’s
mouth or nose and then move into their lungs. Once inside the body, the virus comes in contact
with cells in the throat, nose or lungs. One spike on the virus inserts into a receptor molecule on
the healthy cell membrane, just like the lock-and-key mechanism during acrosomal reaction (during
fertilization) in humans. This action allows the virus to get inside the cell. A typical flu virus would
travel inside a sac made from the cell membrane to the cell’s nucleus that houses all its genetic
material. The coronavirus, on the other hand, doesn’t need to enter the host cell nucleus. It can
directly access parts of the host cell, more specifically, the ribosomes. Ribosomes use genetic
information from the virus to make viral proteins such as the spikes on the virus’ surface. A
packaging structure in the cell (Golgi complex) carries the spikes in vesicles which merge with the
cell’s outer layer – the cell membrane. All the parts needed to create a new virus gathered just
beneath the cell membrane. Then, a new virus begins to emerge from the cell membrane.

Quantitative treatment by means of

biotechnology
Elementary structure

Nucleocapsid (N)
Spike glycoprotein (S)

Membrane protein (M)

Envelope (E)

RNA

Hemagglutinin esterase-
dimer

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 Fig: Elementary representation of SARS-CoV-2 structure

The coronavirus genome is comprised of about 30,000 nucleotides. It encodes four structural
proteins, Nucleocapsid (N) protein, Membrane (M) protein, Spike (S) protein and Envelop (E)
protein and several non-structural proteins (NSPs). Among them, S glycoprotein, with two
domains of S1 and S2, has been as of interest of recent studies, while it is responsible for invasion
and entry into the host cells; the Receptor-Binding Domain (RBD) of S1 interacts with
Angiotensin-Converting Enzyme 2 (ACE2) on the cell surface, while the S2 domain is responsible
for virus-cell membrane fusion and viral entry with higher affinity. The capsid is the protein shell,
inside the capsid, there is nuclear capsid or N-protein which is bound to the virus single positive
strand RNA that allows the virus to hijack human cells and turn them into virus factories.

The N protein coats the viral RNA genome which plays a vital role in its replication and
transcription, and hence are good cells for targeting. Although the pathogenesis of SARS-CoV-2
has not been clearly understood yet, it is found to be a large-enveloped positive-sense RNA virus.
The N-terminal of the N protein which is binding to genomic and sub-genomic RNAs in MHV
and IBV virions and process the viral replication and transcription.

The M-protein is most abundant in the viral surface and it is believed to be the central organizer
for the coronavirus assembly. The S-protein is integrated over the surface of the virus, it mediates
attachment of the virus to the host cell surface receptors and fusion between the viral and host
cell membranes to facilitate viral entry into the host cell. The E-protein is a small membrane
protein composed of about 76 to 109 amino acids and minor component of the virus particle, it
plays an important role in virus assembly, membrane permeability of the host cell and virus-host
cell interaction. A lipid envelop encapsulates the genetic material. Hemagglutinin-esterase dimer
(HE) have been located on the surface of the viral. The HE protein may be involved in virus entry,
is not required for replication, but appears to be important for infection of the natural host-cell.
State-of-the-art cryo-EM experiments have revealed the full structure of the Spike (S) protein in
the close and open (prefusion) states. Such glycoprotein is made of three identical chains with
1273 amino acid each and it is composed by two well-defined protein domain regions: S1 and S2
subunits which are associated to cell recognition and the fusion of viral and cellular membranes
respectively. The latter process occurs through different protein conformational changes that
remain still uncharacterized.

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Fig: a) Schematic representation of the genome organization and functional domains
of S protein for COVID-19. The single-stranded RNA genomes of COVID-19
encode two large genes, the ORF1a and ORF1b genes, which encode 16 non-
structural proteins (nsp1–nsp16). The structural genes encode the structural
proteins, spike (S), envelope (E), membrane (M), and nucleocapsid (N). The
accessory genes denoted in shades of green. The structure of S protein is
shown beneath the genome organization. The S protein is consisting of the S1
and S2 subunits. The S1/S2 cleavage sites are highlighted by dotted lines. In
the S-protein, cytoplasm domain (CP); fusion peptide (FP); heptad repeat
(HR); receptor-binding domain (RBD); signal peptide (SP); transmembrane
domain (TM) are shown
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 b) The viral surface proteins, spike, envelope and membrane, are embedded in
a lipid bilayer. The single-stranded positive-sense viral RNA is associated with
the nucleocapsid protein.

Crystal Structure of COVID-19 Mpro

The COVID-19 replicase gene encodes two polyproteins, pp1a and pp1ab with molecular weight
450 and 750 KD respectively. These polyproteins are required for viral replication and
transcription. In the proteolytic process, the functional polypeptides of spike, membrane, envelop,
nucleoprotein, replicase and polymerase are released from polyproteins. This process was carried
out by a chymotrypsin-fold proteinase namely main protease (Mpro ). The Mpro has a vital role in
polyprotein processing and virus maturation, hence, it is considered to be an attractive target for
antiviral drug design as an approach toward COVID-19 treatment. The Chinese scientists have
first published the genome and with overseas collaboration have obtained the crystal structure of
three-dimensional novel COVID-19 main protease (Mpro ) and deposited in the protein data bank.

Fig: Three-dimensional structure of COVID-19 𝐌𝐩𝐫𝐨

The crystal structure of COVID-19 Mpro has 306 amino acids with the three regions, in the first
region represented in blue contains 8-101 residues, second region in green are 102-184 residues
and third region in orange are 201-303 residues. The first and third regions have an antiparallel β-
sheet structure, third region has five alpha helices arranged into a cluster. The third region is
connected to second region through a long loop region contains 185-200 residues. Mass
spectroscopy determined the weight of COVID-19 Mpro is 33797.0 Da. Theoretical studies
confirmed the weight is 33796.8 Da. Furthermore, in the literature, several crystal structure of
COVID-19 Mpro in complex with different inhibitor are deposited in the protein data bank by
using X-ray diffraction technique at resolution between 1.31 Å and 3.084 Å. On the other hand,

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the HIV-1 protease inhibitors, tipranavir, saquinavir, ritonavir, nelfinavir, lopinavir, indinavir,
darunavir, atazanavir, and amprenavir are widely reported to be able to deactivate Mpro .

E-Protein ion channel activity

The COVID-19 E-protein is a short and integral membrane protein that contains 76-109 amino
acids, size ranging between 8.4 and 12 kDa, consist of 35 α-helices and 40 loops. The protein has
short hydrophilic amino terminus consisting of 7–12 amino acids, followed by a large hydrophobic
transmembrane domain of 25 amino acids long hydrophilic C-terminal domain (shown in box).
The hydrophobic region can generate oligomerization and form an ion-conductive pore in
membranes, it plays a significant role in the assembly of the viral genome. This protein is involved
in several aspects of the virus life cycle, such as assembly, budding, envelope formation, and
pathogenesis. E protein’s ion channel activity is found in the transmembrane region of the protein.
The membrane potential has been regulated by E-protein controlling the ion flow between the
intracellular and extracellular environment. The ion conductivity triggered by E-protein via the
manipulation of COVID-19 genome seems to be a novel route involved in virus pathogenesis.
Although, the E-protein has been interacted with other coronavirus proteins as well as host cell
proteins. E-protein’s ion channel activity and the alteration of coronavirus cell ion balance by E-
protein is a necessary process for virus production but the effect of E-protein ion channel activity
in virus pathogenesis remains elusive.

Few efforts have been found that mutation of the E-protein in the extracellular membrane could
disrupt the ion-conductivity and the normal viral assembly, hence control the E protein dynamics
is a promising target for preventing pathogenesis associated with the COVID-19. For example,
Nieto-torres et al. (2014) have demonstrated that, Mice infected with COVID-19 viruses exhibited
E-protein ion channel activity, with wild-type E-protein sequence, that restored ion transport,
resulting in the mice death with the loss of weight. In contrast, mice infected with mutant E-
protein showed lack of ion channel activity and has result they recovered from the disease and
most survived. This evidence confirmed that ion channel activity correlated well with the virus
growth. The strong E-protein ion channel activity is generated a higher chance for the mortality
of mice is observed. Hence, inhibitor target to E-protein process can help to prevent virus
production. In this respect, Wilson et al., showed that hexamethylene amiloride inhibitor has
shown to block the E-protein ion channel conductance in cell membrane and inhibits replication
of the parent coronavirus in cultured cells. Recently, Gupta et al. (2020) have identified the
medicinal properties of Belachinal, Macaflavanone E and Vibsanol B inhibitors which are
successfully passed the ADMET test and Lipinski’s rule 5 s. These compounds are reduced the
random motion of the human COVID-19 E protein in terms of inhibiting the function of the
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human “COVID-19 E-protein”. So far, our understanding about the mechanism of the E-protein
ion channel activity in the viral assembly is an ongoing debate. This is one of the most important
research topics to investigated which deals with E-protein ion channel activity in viral production
to reduce the mortality rate of diseased human by deletion of E-protein by inhibitor.

The Mechanism of Attack

As mentioned earlier, as the pathogenesis of the virus is not understood, it is, to this day, decided
almost indeterminately that it is a large enveloped, positive-sense RNA virus, similar to other
coronaviruses, which contains several proteins including M (membrane), S (spike), E (envelope),
and N (nucleocapsid), which are good candidates for targeting. The N-terminal of the N protein
which is binding to genomic and sub-genomic RNAs in MHV and IBV virions and process the
viral replication and transcription. This is one of the important open research problems the
developing of an effective drug targeting to prevent the contacts between N-terminal of N-protein
and single positive RNA strand which can stop viral replication and transcription. Sarma et al.
(2020) reported that two important class of compounds, theophylline and pyrimidone drugs as
possible inhibitors of RNA binding to the N terminal domain of N protein of coronavirus, thus
opening new avenues for in vitro validations. With this data, the mechanism of viral entry and
replication and RNA packing in the human cell is now mapped.

Fig: The schematic diagram of the mechanism of COVID-19 entry and viral RNA
packing in the human cell
The coronavirus spike (S) protein attaches to angiotensin converting enzyme 2 (ACE2) receptors
that is found on the surface of many human cells, including those in the lungs allowing virus entry.
The coronavirus S protein is subjected to proteolytic cleavages by host proteases (i.e. trypsin and

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furin), in two sites located at the boundary between the S1 and S2 subunits (S1/S2 site). In a later
stage happens the cleavage of the S2 domain (S2′ site) in order to release the fusion peptide.
This event will trigger the activation of the membrane fusion mechanism. Searching for antibodies
can find support on molecular targeting which can utilize the structural information (aa sequence)
of the binding region which is found in angiotensin-converting enzyme 2 receptor. In this way this
protocol could device a treatment to block the viral entry. Typically, human cell ingests the virus
in a process called endocytosis. Once entered the cytoplasm, it has been suggested most likely that
COVID-19 employs a unique three-step method for membrane fusion, involving receptor-binding
and induced conformational changes in Spike (S) glycoprotein followed by cathepsin L proteolysis
through intracellular proteases and further activation of membrane fusion mechanism within
endosomes. Then, the endosome opens to release virus to the cytoplasm, and uncoating of viral
nucleocapsid (N) is started via proteasomes which typically can hydrolyse endogenous proteins,
but they are also capable of degrading exogenous proteins such as the SARS nucleocapsid protein.
A different two-step mechanism has been suggested and in this case the virion binds to a receptor
on the target host cell surface through its S1 subunit and the Spike is cleaved by host proteases
and then it is expected the fusion at low pH between viral and host target membranes via S2
subunit. Finally, the viral genetic material a single stranded RNA is fully released into the
cytoplasm. There takes place the replication and transcription processes which are mediated by
the so-called replication/transcription complex (RTC). Such complex is encoded in the viral
genome and it is made of non-structural proteins (NSP). The RTC is believed to induced double-
membrane structures in the cytoplasm of the infected cell. Following the positive RNA genome is
translated to generate replicase proteins from open reading frame 1a/b (ORF 1a/b). These
proteins use the genome as a template to generated full-length negative sense RNAs, which
subsequently serve as templates in generating addition full-length genomes. Structural viral
proteins, M, S and E are synthesized in the cytoplasm and then inserted into the endoplasmic
reticulum (ER), and transfer to endoplasmic reticulum-Golgi intermediate compartment (ERGIC).
Also, in the cytoplasm nucleocapsids are formed from the encapsidation of replicated genomes by
N protein, and as a result they coalesce within the ERGIC membrane in order to self-assembly
into new virions. Finally, novel virions are exported from infected cells by transport to the cell
membrane in smooth-walled vesicles and then secreted via a process called exocytosis, so that can
infect other cells. In the meantime, the stress of viral production on the endoplasmic reticulum
eventually leads to cell death. However, the mechanism of action for novel COVID-19 is still
unknown.

Qualitative treatment
Diagnosis
Nasal swab test and antibody tests (including RT-PCR) are used to diagnose corona virus.

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Symptoms
COVID-19 affects different people in different ways. Most infected people will mild to moderate
illness and recover without hospitalization. On average it takes 5–6 days from when someone is
infected with the virus for symptoms to show, however it can take up to 14 days.
The main symptoms include: Fever, Coughing, Shortness of breath, Trouble breathing, Fatigue,
Chills, sometimes with shaking, Body aches, Headache, Sore throat, Congestion/runny nose, Loss
of smell or taste, Nausea, Diarrhea, the most serious symptoms being chest pain, loss of speech
or mobility and/or confusion.

SERIOUS COVID-19 SYMPTOMS REQUIRING IMMEDIATE MEDICAL CARE

Fig: WHO’s advice to the public on COVID-19 symptoms

The less common symptoms include: a rash on skin, red or irritated eyes, discoloration of fingers
or toes. The virus can also lead to pneumonia, respiratory failure, heart problems, liver problems,
septic shock, and death.

Elementary review of the development of pneumonia symptoms

A clearer concept of this can be achieved by focusing on the lungs. Each lung has separate sections
called lobes. Normally, as we breathe, air moves freely through the trachea or wind pipe, then
through large tubes called bronchi, through smaller tubes called bronchioles and finally into tiny
sacs called alveoli. Our airways and alveoli are flexible and springy.

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When we inspire, each alveolus inflates like a small balloon, and when we expire, the sacs deflate.
Small blood vessels called capillaries surround the alveoli. Oxygen from the inspired air passes into
the capillaries and then carbon dioxide from the body passes out of the capillaries into the alveoli,
and then excreted out through expiration. Our airways catch most germs in the mucus that lines
the trachea, bronchi and bronchioles. In a healthy body, hair-like cilia lining the tubes constantly
push the mucus and germs out of the airways where these are expelled by coughing.
Normally, cells of our immune system attack viruses and germs that make it past the mucus and
cilia and enter the alveoli. However, if the immune system is weakened, like in the case of a corona
virus infection, the virus can overwhelm the immune cells, and the alveoli and bronchioles become
inflamed as the immune system attack the multiplying viruses. The inflammation can cause the
alveoli to fill with fluid, making it difficult for the body to get the oxygen it needs. Low burn
pneumonia is a possibility, where one lobe of the lungs is affected. Another possibility is
bronchopneumonia, which affects many areas of both lungs. Pneumonia may cause difficulty
breathing, chest pain, coughing, fever and chills, confusion, headache, muscle pain and fatigue. It
can also lead to more serious complications like respiratory failures, which occur when breathing
becomes immensely difficult that a ventilator is required to facilitate breathing. These are the
machines that save lives and that medical device companies currently ramp up production for. The
probability of developing these symptoms depends on a lot of factors, like age, existing medical
conditions, etc.

Treatment
The antiviral medication called remdesivir (Veklury) is the first medication to get FDA approval
for treatment of patients hospitalized with COVID-19.

Fig: Structure of Remdesivir

Preventions
To prevent infection and to slow transmission of COVID-19, do the following:
 Get vaccinated when a vaccine is available to you.

 Stay at least 1 metre apart from others, even if they don’t appear to be sick.

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  Wear a properly fitted mask when physical distancing is not possible or when in poorly
ventilated settings.
 Make sure your mask covers your nose, mouth and chin.
 Clean your hands before you put your mask on, before and after you take it off, and
after you touch it at any time.
 When you take off your mask, store it in a clean plastic bag, and every day either
wash it if it’s a fabric mask or dispose of it in a trash bin if it’s a medical mask.
 Don’t use masks with valves.
 Choose open, well-ventilated spaces over closed ones. Open a window if indoors.
 Wash your hands regularly with soap and water or clean them with alcohol-based hand
rub. Keep good hygiene. Clean and disinfect surfaces frequently, especially those which
are regularly touched, such as door handles, faucets and phone screens.
 Cover your mouth and nose when coughing or sneezing.
 If you feel unwell, stay home and self-isolate until you recover.

Vaccination
Government of India allowed two vaccines in our country: Covishield and Covaxin.
 Covaxin, India's indigenous COVID-19 vaccine by Bharat Biotech is developed in
collaboration with the Indian Council of Medical Research (ICMR) - National Institute
of Virology (NIV). It is an inactivated vaccine, which has been prepared on a tried and
tested platform of dead viruses. This vaccine is developed with Whole-Virion Inactivated
Vero Cell-derived technology.
 Covishield vaccine (Oxford - Astra Zeneca vaccine) manufactured locally by the Serum
Institute of India, the world's largest vaccine manufacturer. It is made from a weakened
version of a common cold virus (known as an adenovirus) from chimpanzees. It comes
under attenuated vaccines.

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 Effect of COVID-19 on Cancer Patients
A patient with cancer has a higher risk of having severe symptoms of COVID-19. Ex-cancer
patients are also at higher risk of severe
COVID-19. Other factors that increase
the risk for severe COVID-19 include
having a weakened immune system
(being immunocompromised), older
age, and other medical conditions.
People with blood cancers may be at
higher risk of prolonged infection and
death from COVID-19 than people
with solid tumors. That is because
patients with blood cancers often have
abnormal or depleted levels of immune
Fig: Connections between cancer drivers
cells that produce antibodies against
viruses.

The risk
Cancer treatments like chemotherapy and immune suppressants taken after surgical cancer
removal usually weaken the patient’s immune system. This means that any infection around may
possibly affect you more than any healthy individual. For the people still undergoing
chemotherapy, it is all the more challenging. Even amongst cancer patients, children are at
maximum risk of getting affected due to this infection.
Safety in people with cancer
Experts agree that the COVID-19 vaccine is recommended for people with cancer, cancer
survivors, and those currently on cancer treatment, including chemotherapy and immunotherapy.
The best available evidence suggests the odds of dying or experiencing severe complications from
COVID-19 are nearly 2 times higher if you are someone with cancer than a person without cancer.
The only people who should not be offered the vaccine are those who may have a harmful reaction,
such as anaphylaxis, to a specific vaccine component. Talk with your doctor or your cancer care
team about whether a COVID-19 vaccine is recommended for you, based on your own medical
history. Even though the original COVID-19 vaccine clinical trials did not specifically include
people with cancer, including the pneumococcal pneumonia vaccine and the flu vaccine. Some
vaccines are OK to receive during cancer treatment, when the immune system is weak, but some
vaccines, such as live virus vaccines, should not be given during cancer treatment. The COVID-
19 vaccines are not live virus vaccines and may be given during or after cancer treatment.

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 Protection against the virus
Considering the fact that the immune system is affected by the SARS-CoV-2, immune-based
treatment, including corticosteroids, monoclonal antibodies against pro-inflammatory cytokines,
plasma therapy, and intravenous immunoglobulin was practiced in some patients in a few studies.
However, the efforts should not be limited to such treatments, while novel therapeutic approaches
could be considered, using medical biotechnology. Such pandemics are a complex problem, which
needs transdisciplinary studies.

Vaccine development
Studies of other corona viruses led most researchers to assume that people who have recovered
from a SARS-CoV-2 infection could be protected from reinfection for a period of time, but that
assumption needs to be backed by empirical evidence, and some studies suggest otherwise. There
are several different approaches for a potential vaccine against the corona virus; the basic idea is
to receive a shot containing faint versions of the virus. The vaccine would expose our body to a
version of the virus that is too weak to cause infection but just strong enough to stimulate an
immune response. Within a few weeks, cells in the immune system would create antibodies which
would be specific for only the corona virus, or specifically, its spike protein. Antibodies then attach
to the virus and prevent it from attaching to the host cells. The immune system then responds to
signals from the antibodies by consuming and destroying the clumps of viruses. If the real virus is
contracted at a later stage, the body will recognize it and destroy it, hence being primed. Collecting
evidence on whether this would be possible, safe and effective is part of what had taken researchers
a long time to develop a vaccine.

Fig. COVISHIELD
A potential solution for monitoring severity of COVID-19 patients
Application of Artificial Intelligence (AI) is revolutionizing various sectors including
healthcare. Innovators are already using AI to deliver better health-related facilities for the masses
through Apps. AI is marching forward in the medical field. A start-up Predible Health Pvt. Ltd
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has come up with an innovation called Lung IQ. This innovation is a holistic AI-based application
for the diagnosis and monitoring of respiratory conditions. The solution enables early detection
of lung cancer, characterization of chronic obstructive pulmonary diseases and monitoring of
interstitial lung diseases. This innovation has been developed by using large proprietary datasets
with customized algorithms for detection, qualification and diagnosis. It is compatible with all
kinds of CT 8 scanners. It can help radiologists detect and quantify findings better in daily practice.
It is also available as a joint solution with teleradiology for an end-to-end reading. The DBT’s
public sector undertaking Biotechnology Industry Research Assistance Council (DBT-BIRAC) is
supporting the innovation. It is a potential solution for monitoring the severity of COVID-19
patients. It can help radiologists detect, quantify and communicate COVID-19 findings from Lung
CT images. The findings of COVID-19 are very similar to that of other infectious and
inflammatory diseases and this ready-to-use product can be helpful in the fight against COVID-
19 pandemic.

Trial test of the FDA-approved drugs for COVID-19

patients
Nowadays, the drug repurposing has been used to identify potential drugs against
coronavirus. Enormous efforts have been paid for the ability to reuse FDA approved/preclinical
trial drugs for the disease. In the literature, we find several promised drugs candidate targeted to
multiple virus protein (Graham et al., 2013; Khan et al., 2020; Yang et al., 2003). The WHO has
provided the permission to doctors and scientist carry out the trial test with the combination of
different FDA-approved drugs for COVID-19 treatment. In the view of urgency and current need,
to reduce the cost, time and risks of the drug development process, scientists are involved in
reusing already approved drug candidates to test in COVID-19 patients. In a short time, the
response of the scientific community is such that involve enormous efforts to develop a novel
therapy and treatment. For example, Chloroquine and Hydroxychloroquine, old drugs, have been
used to treat malarial, rheumatoid arthritis, lupus and sun allergies for more than sixty years. The
activity of hydroxychloroquine on viruses is probably same as that of chloroquine since the
mechanism of the action of these two molecules is identical. Chloroquine as an antimalarial and
autoimmune disease drugs has shown a synergistically enhancing effect as antiviral drugs in vivo
studies (Savarino et al., 2006; Yan et al., 2013). It interferes with terminal glycosylation of cellular
receptor, angiotensin-converting enzyme 2. This may negatively influence-receptor binding and
abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting the
spread of SARSCov in cell culture has been prevented (Vincent et al., 2005).
The hydroxychloroquine has shown a potent efficacy in treating patients with COVID-19
pneumonia. More than hundred patients showed the superiority of chloroquine compared with
treatment of standard care in terms of reduction of exacerbation of pneumonia, viral load and
symptoms. Colson group have suggested that chloroquine and hydroxychloroquine as available
weapons to fight COVID-19 (Colson et al., 2020). In 2014-2017, ivermectin antiviral drug used
for phase 3 treatment of dengue infection, daily oral dose significantly reduced in serum level of

Page 17
viral NS1 protein. Caly et al. (2020) have demonstrated Ivermectin-treatment can reduce ∼5000-
fold viral RNA load compared to the control sample in cell cultural at 48 h, but no further
reduction observed at 72 h.
Mulangu et al. (2019) have conducted a trial of four investigational therapies for Ebola virus
diseased patients. A total of 681 patients were registered between November 18, 2018 and August
9, 2019. The patients were assigned 1:1:1:1 ratio to receive ZMapp (a triple monoclonal antibody
agent), remdesivir (a nucleotide analogue RNA polymerase inhibitor), Mab114 (a single human
monoclonal antibody derived from an Ebola survivor), and REGN-EB3 (a coformulated mixture
of three human IgG1 monoclonal antibodies). Both Mab114 and REGN-EB3 groups were
superior than ZMAP and remdesivir group in reducing mortality for Ebola patients, primary
groups have faster rate of viral clearance than later groups. Remdesivir has been promised antiviral
drug against RNA viruses, including SARS/MERS, in cultured cell, mice and nonhuman primate
model. It is under the clinical development for Ebola virus treatment and typically it is distributed
in the entire human body including lung after oral administration. Sheahan et al. (2017) tested a
Remdesivir inhibitor that has shown activity against Ebola virus as a potential agent to be used to
combat coronaviruses. Unfortunately, it could not be help to Ebola patients during the 2019
outbreak in the Democratic Republic of the Congo. A coronavirus research at the university of
Iowa suggested that Remdesivir antiviral acting much more potential if patient takes it early,
patients with mild symptoms. Importantly, M. Wang et al. (2020) study reported that remdesivir
and chloroquine are highly effective in the control of COVID-19 infection in vitro experiments.

Fig: Structure of REGN-EB3

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 The first COVID-19 patient, 35-year-old in Washington, admitted to a hospital on 15 January
2020, in the united states because of dry cough, two-day history of nausea and vomiting. He
reported that he had no shortness of breath or chest pain. The important signs, fever, cough,
rhinorrhea, fatigue, nausea, vomit, diarrhea and abdominal discomport, were in normal condition.
He had high fever 39.4° C with cough at the eleventh day of hospitalized, on the evening of same
day, clinical began treatment with intravenous remdesivir, next day, his clinical condition had
improved. As January 30, he was still hospitalized but his symptoms had resolved exception of
cough, which has decreased in severity.
Cao et al. (2020) have conducted trial test using lopinavir-ritonavir antiviral drugs for
COVID-19 patients. A total of 199 patients were enrolled for the test, 99 patients were assigned
to the lopinavir-ritonavir group, remaining 100 patients to be treated in the standard care group,
resulting the mortality rate was similar in both lopinavir-ritonavir group and standard care group.
They found that lopinavir-ritonavir treatment failed to significantly accelerate clinical
improvement, reduce mortality, diminish throat viral RNA detectability in patients with serious
COVID-19. In case of the severe COVID-19 adult patients, no benefit was observed with
lopinavir-ritonavir treatment in comparison to the standard care group. Such study has found that
lopinavir-ritonavir does not seem to be effective for COVID-19 patients and these combinations
has produced more side effects (Cao et al., 2020). In summary, the antiviral drugs, alone and in
combination, have been tested in human body, all showed some evidence of effectiveness against
SARS and MERS, they seem not to be effective for COVID-19 (Baden & Rubin, 2020).
Azithromycin has been displayed an antiviral property against Zika and Ebola virus in vitro.
It can prevent severe respiratory tract infection in the case of viral infected patients. Gautret group
have treated successfully chronic disease patients with long-term hydroxychloroquine medicines
with 600 mg per day for 12 to 18 months. As 17 march 2020, A paper reported (Gautret et al.,
2020), they are monitored the viral load in the COVID-19 patients with and without receiving
drugs for the six days. They have examined a total of 36 patients, 20 hydroxychloroquine-treated
patients and 16 control patients. Among hydroxychloroquine-treated patients, six patients received
azithromycin with 500 mg on day 1 followed by 250 mg per day for the next four days. At day 6,
100% patients treated with hydroxychloroquine and azithromycin combination have cured
comparing with 57.1% in patients treated with hydroxychloroquine only, and 12.5% in the control
group. Finally, they found that hydroxychloroquine and azithromycin combination have cured the
COVID-19 patients but the drawback of this study is used a very small size of survey.

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 Fig: Structure of Azithromycin
Z. Jin et al. (2020) have screened a library of ∼10,000 compounds which are consisting of
approval drugs, clinical trial drugs and natural products. They were used combined structural-
based abinitio, drug design, and high-throughput screening to identified two drugs of these
compound are Ebselen and thiadiazolidinone-8 (TDZD-8). Quantitative real-time RT-PCR
demonstrated that in comparison to treatment in the absence of inhibitor, treatment of Ebselen
reduced the amount of COVID-19 by 20.3-fold, and TDZD-8 and N3 (N3 inhibitor designed by
Z. Jin et al. (2020) that can inhibit multiple Coronavirus Mpro S including those from COVID-19
and MERS-CoV) showed 10.9-fold and 8.4-fold reduction in COVID-19 growth, respectively.
These data suggested that Ebselen as a potential antiviral inhibitor for COVID-19 treatment.
Doctor’s team reported, a large doses of the flu drug oseltamivir combined with HIV drugs
lopinavir and ritonavir could improve the conditions of several COVID-19 patients at the Rajavithi
Hospital in Bangkok. Based on the report, Gromica et al., have utilized computational docking
approach to analysed the effect of synergism of these drugs against the COVID-19 main protease.
They found that the combination of three drugs, lopinavir, oseltamivir and ritonavir, showed a
better binding energy than that of individual drug, and they reported the protein in complexed
with three drugs are stable during the simulations.
The CPAM (China international exchange and promotive association for medical and health
care) recommends to take lopinavir 400 mg, ritonavir 100 mg (two tablets by mouth twice in daily)
or chloroquine (500 mg tablet by mouth twice in daily) for older patients or patients with under
underlying conditions and serious symptoms. In case chloroquine is unavailable, consider to use
of hydroxychloroquine (400 mg by mouth once daily). It cannot be recommended to take ribavirin

Page 20
and interferon drug because of the high risk for side effects but these drugs may be considered if
treatment with lopinavir, ritonavir, chloroquine or hydroxychloroquine are ineffective. To this end,
some drugs have become promises, other are being ruled out including lopinavir and ritonavir,
mix of two drugs used to treat HIV disease. So far, trial test results are confirmed as FDA-
approved therapeutics or drugs have not helped to treat, cure or prevent COVID-19.

Fig: Structure of Chloroquine

IUPAC nomenclature: (RS)-N’-(7-chloroquinolin-4-yl)-N,N-diethyl-pentane-1,4-
diamine

Fig: Structure of Hydroxychloroquine

IUPAC nomenclature: 2-[4-[(7-chloroquinolin-4-yl)amino]pentyl-ethylamino]ethanol

India’s role in biotechnology in the fight

against the COVID-19 Pandemic
India’s response to the coronavirus pandemic has highlighted the country’s strengths as well
as its weaknesses. Though it is not obvious to most people, every facet of what a country needs to
detect, diagnose, and respond to biological threats like pandemics requires scientific research and
technical capacity that can be mobilized at large scale. In India, the scale is almost unimaginably
large. To their credit, Indian researchers, innovators, and regulators have come together to
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introduce low-cost diagnostics, develop therapeutics, and conduct research to create safe and
effective vaccines during the COVID-19 pandemic. However, these communities have faced
several challenges during different stages including discovery, research and development, clinical
trials, or commercialization of their products, which became acutely apparent around May 2021.
The DBT’s Centre for DNA Fingerprinting and Diagnostics (CDFD) Hyderabad, has
entered into a Memorandum of Understanding with Nizam Institute of Medical Sciences (NIMS)
for a joint project on genomic analysis of SARS-CoV-2 sequence in Indian patients.

Fig: CDFD, Hyderabad

The Hyderabad-based premier scientific institution, which is involved in COVID-19 testing
for samples from Telangana, has also so far tested over 8,500 samples. It had started testing on
COVID-19 samples on 18th April 2020 after due approval from DBT and Indian Council of
Medical Research. It was nominated by the Office of Director, Medical Education, Government
of Telangana along with CSIR-CCMB and ESIC as a centre for pooling of samples from selected
districts of Telangana with less than 2% prevalence of COVID-19 positive cases. Subsequent to
an advisory issued by ICMR on 2nd April 2020, notifying that it has no objection to initiation of
COVID-19 testing in laboratories operating under the DBT, CDFD had reorganised the
infrastructure to create a designated COVID-19 testing laboratory, procured testing kits and
personal protective equipment, and trained the manpower. Senior scientists Dr Ashwin Dalal, Dr
Murali Bashyam, Dr Rashna Bhandari, and Dr Harinarayanan are supervising and providing
leadership to the task with support from the staff and students. Volunteers were trained at CSIR-
CCMB and Osmania Medical College Koti, Hyderabad to conduct RNA preparation and RT-PCR
analysis of samples received from different regions of Telangana. It has, among other things,
drawn-up detailed standard operating procedures for the COVID-19 testing facility set up at its
campus. The document has been prepared based on inputs from different recommendations by
the World Health Organisation, United State’s Centers for Disease Control and Prevention (CDC),
and the handbook prepared by the office of the Principal Scientific Advisor to the Government
of India for COVID-19 testing in research laboratories. It covers all aspects beginning from how
the security guard of the Institute must receive the vehicle carrying samples at the entrance of the
building to how the samples will be analysed and a report sent to the office of the district medical
Page 22
and health officer from where the specific sample had come. It also gives clear protocol for how
the biohazardous waste produced in the process should be handled and disposed of, how to
sanitise the work and how to protect those engaged in the analysis from getting exposed to the
virus.

DBT-ILS establishes in-vitro culture facility for coronavirus

The DBT’s Bhubaneswar-based Institute of Life Sciences (ILS) has established an in-vitro
culture facility for coronavirus. The cultures are from patient sources using vero cells. Seventeen
virus cultures have been established from swab samples with varying virus loads. Dr Soma
Chattopadhyay and Dr Gulam Syed at the Institute are taking the lead in establishing and
maintaining these culture units. This measure will be of great importance for COVID-related
research in the country. In addition, it will aid the industry for appropriate testing and validation
of various antiviral products thereby contributing to diagnostics, pathological intervention, as well
as management of the disease. This facility is in addition to a biorepository facility at ILS, which is
aimed at collecting and storing clinical samples for furthering research and development related to
coronavirus. ILS is the fourth lab to set up such an in-vitro culture facility in India.

Fig: Institute of Life Sciences, Bhubaneswar

Highlights & regulatory measures

 Diagnostics in India
A great deal of collaboration amongst researchers, private sector, and the regulatory
community has been observed during the coronavirus pandemic. Support from the
regulatory authorities motivated several academic and private labs to develop diagnostic kits
indigenously. However, experts argued that India still imports most testing kits. The need
for imports stems from a quantitative shortage of production capacity and qualitative

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 problems in ensuring that indigenous kits are reliable. Experts suggest that regulators and
researchers should work more closely to develop diagnostics that meet international
standards.
 Vaccine Development in India
The coronavirus pandemic has brought to the forefront the potential of the scientific
community and the private sector to develop and manufacture vaccines in a limited time
frame. During the initial stages of the pandemic, Indian vaccine companies were trying to
import vaccine development technology and only conduct clinical development in India.
But within a year, India has developed a few vaccines indigenously. However, a few
academicians believe that the regulatory system in India, in light of the pandemic, is not
fully conducive for smaller firms to fast-track potential candidates, given lack of resources
and a clarity of path, thereby constricting the scope of vaccine manufacturing and delivery
in India. They therefore suggested that whenever the pandemic is controlled, Indian
researchers, industry, and government should assess the impediments to indigenous
discoveries, production, and distribution and create strategies to overcome them.
 Therapeutic Interventions in India
India has been the generics pharmacy to the world. But the coronavirus pandemic has
exposed deep fault lines in India’s healthcare capacity to treat people. These shortcomings
derive from the generally poor status of public health infrastructure in India. Experts
highlighted that in addition to developing safe and effective drugs, India needs to invest in
manufacturing personal protective equipment, scaling up oxygen supply, developing new
medical infrastructure, and building a cohort of healthcare workers to ensure availability
and resilience in the system.
 Digitization of Health Data in India
Experts underscored the importance of an urgent charter for digitized health data in India.
They emphasized that IT companies and public-private partnerships across the country can
be deployed to digitize health data. They emphasized yet again that data standardization, a
procedure to bring data into a common format for collaborative research, analytics, and
sharing of methodologies is critical to pandemic preparedness and response. This can help
us solve a variety of challenges that people faced during the current pandemic, they
highlighted.

 Disease Surveillance in India

Experts underscored that India has too many silos for surveillance of infectious diseases.
There are multiple organizations across the local, state, and national level that collect data
for the same disease but with differing case definitions and limited coordination. This leads
to different disease numbers being reported under different programs, according to experts.
They therefore highlighted the need for India to invest in an integrated disease surveillance
mechanism with better data sharing protocols. They also discussed the importance of

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 public-private collaboration to setup centres that can sequence pathogens which can lead
to timely detection of outbreaks. However, they discussed that reliance on imports for
reagents and lack of skilled people have constrained India’s capacity to scale up their
sequencing efforts. They underlined that India should invest in developing quality reagents
indigenously to broaden the scope of genome sequencing.
 South-South Cooperation in Health
Scientists in India are in collaboration with researchers in other developing countries such
as Brazil and Cuba which have relatively strong biotechnology capacity. An enabling
community has been provided to the academic community – both public and private – for
them to come up with solutions that can be used for pandemic preparedness and response.

Response to the COVID-19 Pandemic:

Catastrophic Failures of the Science-Policy
Interface
The science-policy interface is a short-hand description of the system by which the best
scientific information and advice is provided by the most knowledgeable institutions and experts,
acted upon by key decision-makers in government, and provided to the public. Catastrophic
failures of the science-policy interface in many countries and globally have led to disastrous
outcomes for public health, the economy, and international collaboration. Many of the failures are
due to incompetence in government, but there have also been failures by scientific institutions and
advisors who recognized the emerging threat but were unable to marshall support for timely
effective action.
The initial missteps have been costly as top government leaders downplayed or covered up
the crisis in the beginning. Well documented are failures by
(i) the Chinese government to alert the world early and quickly supply diagnostic data,
infection statistics, and World Health Organization (WHO) access and
(ii) the United States government to take timely mitigation action and employ early testing.
Mistakes in early action occurred elsewhere as well, including in the United Kingdom,
several countries in the European Union, and at WHO.
Misinformation campaigns by some government leaders and actors on social media created public
confusion and delayed action. If all governments had acted early and in unison, the public health
and economic impacts would have been far less. This global pandemic is the first truly global crisis
in history, affecting virtually every person on the planet at approximately the same time.
That so many advanced countries with highly capable science advisory ecosystems had
failures and were unable to act wisely and early is astounding. This outcome is especially surprising

Page 25
since the worldwide public health community was very much aware of the threat of pandemics
coming from experience with 2003 SARS, MERS, Ebola, Avian Flu, and knowledge of pandemics
throughout history. The significant threat to the world posed by a new pandemic was also well
known by many scientists, economists, health experts, and security professionals inside
governments. Plans and preparations were on the shelf.
Dealing with this powerful adversary illustrates what can be lost if the science advisory
systems at the national and global levels are flawed and political leaders do not listen to highly
expert scientific advice. Of course, politicians have to include other factors besides science in their
decisions, but ignoring science until a crisis is a prescription for disaster. Notably, there have been
some successes in dealing with COVID-19 that illustrate it is possible for nations to harness the
best scientific advice and take effective action. Positive examples include Singapore, Taiwan,
Republic of Korea, Austria, and Germany. Medical experts have pointed to the importance of
robust public health care systems, early diagnosis through early broad-based testing, etc.
Efforts at global cooperation at the nation-state level have been incomplete at best. The
leaders of the G7 in March issued a communique committing to a strong global response to the
COVID-19 pandemic through closer cooperation and enhanced coordination of efforts. It said
“we will increase coordinated research efforts, including through support for the global alliance
Coalition for Epidemic Preparedness and Innovation (CEPI)” and “support the launch of joint
research projects…and the sharing of facilities.” Yet ongoing disagreements between many
governments continue to affect the ability to optimize responses to the pandemic, maintain access
to medicines and medical supplies, and support scientific collaboration and information sharing.
The global effort to tackle the COVID-19 pandemic has been hampered by political conflicts
between the U.S. and China. The accelerating “tit for tat” between the leaders has been a self-
inflicted wound on both countries. The G7 communique did not mention China. Collaboration
among all nations is especially needed to assist the poorest countries as the virus spreads. These
countries are at even greater risk of enormous suffering and potential societal collapse.
The worldwide science and technology communities in the public and private sectors have
been mobilized to deal with the pandemic, rapidly advancing the development of new diagnostics,
therapeutics, and potential vaccines. International cooperation with initiatives and funding on
vaccines—such as through GAVI (the vaccine alliance), CEPI, and private foundations—working
with promising vaccine developers have helped to accelerate progress. Experts have also provided
their advice in public fora. Even with worldwide collaboration of scientists in many fields,
roadblocks to international scientific collaboration have been growing in recent years. Scientific
collaboration between the U.S. and China has been under siege. The Chinese government caused
a backlash in the U.S. with clandestine programs employing some of their scientists to use research
collaborations to steal technologies and research information in ways antithetical to the accepted
norms of scientific collaboration. Scientific communities are clear that this behavior is a threat to
scientific collaboration and must end. U.S. scientists have also feared that the current
administration would overreact with new policies having considerable negative impact: restricting

Page 26
scientific collaborations, causing top foreign scientists working in the U.S. to leave, and halting the
flow of bright scientists from other countries to pursue education, training, and research in
American institutions. All scientists need to help their governments to find the right policies to
permit scientific collaboration to go forward. The right policies include governments and scientific
institutions ensuring that accepted norms of transparency and ethics in scientific collaboration are
followed and enforced. Also essential is continuing the policy that to the greatest extent possible
the products of fundamental research should remain unrestricted.
The science-policy interface at the international level for dealing with all of our global
challenges has shown weaknesses and successes. A positive development long before the current
crisis came from the creation of the Intergovernmental Panel on Climate Change (IPCC). It has
been a partnership of the worldwide scientific community, national governments, and the U.N.
for understanding the implications of anthropogenic climate change and policies that could help
mitigate the damages. This partnership helped lead to the Paris Climate Agreement. Another
positive development came in 2015 from the diplomats who negotiated the seventeen Sustainable
Development Goals (SDGs) as part of the UN 2030 Agenda. They wisely recognized that the
science-policy interface had to be strengthened at the national and global level. The Technology
Facilitation Mechanism (TFM) was created as part of the 2030 Agenda to provide advice on how
to harness better knowledge from science, technology, and innovation (STI) to achieve the
seventeen SDGs. All of our international institutions should accelerate their efforts to incorporate
high quality science advisory mechanisms and utilize them to confront our many global challenges.

Fig: IPCC – Intergovernmental Panel on Climate Change

The hope is that the current political tensions and the pandemic will not cause further
roadblocks to building better science advisory ecosystems, within countries and globally, and to
strengthening international scientific partnerships and collective action. That collaboration—
currently being accelerated in the global scientific enterprise to defeat SARS-COV-2—is needed
for all countries to deal with these global challenges as well as for advancing science to improve
the lives of all people and protect our planet.

Page 27
 Conclusion
The coronavirus was responsible for the Covid-19 pandemic. It is an infectious disease that
has affected millions of people’s lives. The pandemic has impacted people all across the world in
diverse ways. It was first discovered in Wuhan, China, in 2019. However, the World Health
Organization (WHO) proclaimed it a pandemic in March 2020, claiming that it has spread
throughout the globe like wildfire. The pandemic has claimed the lives of millions of people. The
virus had negative consequences for those who were infected, including the development of a
variety of chronic disorders. The main symptoms of this disease were loss of smell and taste,
fatigue, pale skin, sneezing, coughing, oxygen deficiency, etc. Because Covid-19 was an infectious
disease, all those who were infected were instructed to segregate themselves from those who were
not. The folks who were affected were separated from their families and locked in a room. The
government has prioritised people’s safety. The frontline personnel were like superheroes, working
tirelessly to ensure the public’s safety. For the sake of their patients’ and close relatives’ safety,
many doctors had to stay away from their families and babies. The government had also taken
significant steps and implemented different protocols for the protection of people.

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The following sources have been referred to for the entirety of the project:
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https://www.sciencediplomacy.org/editorial/2020/response-covid-19-
pandemic-catastrophic-failures-science-policy-interface
 Cover page Quote : The Good Doctor (TV Series) Season 4
 https://www.hopkinsmedicine.org/health/conditions-and-
diseases/coronavirus
 https://my.clevelandclinic.org/health/diseases/21214-coronavirus-covid-19
 Varsity Education Management Limited, Biology XII Volume II Part A
 All chemistry Structures – ChEBI, PubCHEM, Opsin
 SARS-CoV-2 picture: https://www.who.int/health-
topics/coronavirus#tab=tab_1
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for-public
 https://www.cancer.gov/about-cancer/coronavirus/coronavirus-cancer-
patient-information
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people-with-cancer-need-know
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against-covid-19-pandemic-event-7633
 Varsity Education Management Limited, Biology XII Volume II Part D
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377401/
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 Picture of cancer: https://scitechdaily.com/cancer-breakthrough-
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 https://www.youtube.com/watch?v=5DGwOJXSxqg
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