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. [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. Page 2Table of Contents Acknowledgement COVID-19: An Overview... Quantitative treatment by means of biotechnology .... Elementary structure. LAY 5 Crystal Structure of COVID-19 MP, 8 rotein ion channel activity . , 9 The Mechanism of Attacks wt \ so 10 Qualitative treatment... Diagnosis. AK..Y soca Symptoms senna . 2 Treatment Mh.) ew B Preventions in 8 Vaccination 4 Effect of COVID-19 on Cancer Patients... The risk ® 15 Safety in people with cancer 15 Protection against the virus... Vaccine development nnn 16 Trial test of the FDA-approved drugs for COVID-19 patients. v7 India’s role in biotechnology in the fight against the COVID-19 Pandemic Response to the COVID-19 Pandemic.. Conclusion Bibliography Page 3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 coinected 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-CoY-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 Page 4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 nuilets, 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’ sutface. 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 Rew vitus 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 Page 5Fig: Elementary representation of SARS-CoV-2 structure The coronavirus genome is comprised of about 30,000 nucleotides. Tt 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 $1 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 $2 domain is Fesponsible 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 tole"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, itis found to bea 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 proc s the viral replication and transcription, ‘The M-protein is most abundant in the viral surface and ic 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 76to 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 itis composed by two well-defined protein domain regions: $1 and $2 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, Page 6Fig: (a) SARS-CoV2 3a Ta S'UTR UTR ~~ 74 8b 9b SARS-CoV2 S-protein }-—-— S1 subunit ———++—— 2 subunit. ———| RBD 1.195 __1.255 Tui] [urafray 1B a Spike Glycoprotein Hemagglutinin-esterase dimer ----Membrane protein ~~- Nucleocapsid protein and RNA > Envelop protein 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 SI 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 Page7b) viral surface proteins, spike, envelope and membrane, are embedded in alipid bilayer. The single-stranded positive-sense viral RNA is associated with the nucleocapsid protein. Crystal Structure of COVID-19 MPr° The COVID-19 replicase gene encodes two polyproteins, ppla and pplab 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 pro out by a chymotrypsin-fold proteinase namely main protease (MP). The MP" 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 efystal structure of three-dimensional novel COVID-19 main protease (MP) and deposited in the protein data bank. was carried Region 3 Region 2 Region 1 Fig: Three-dimensional structure of COVID-19 MP"? ¢ of COVID-19 MP 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 8 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 MP is 33797.0Da, ‘Theoretical studies confirmed the weight is 337968 Da. Furthermore, in the literature, veral crystal structure of COVID-19 MP* in complex with different inhibitor are deposited in the protein data bank by On the other hand, using X-ray diffraction technique at resolution between 1.31 A and 3.08: Page 8the HIV-1 protease inhibitors, tipranavir, saquinavir, ritonavir, nelfinavir, lopinavir, indinavir, darunavir, atazanavir, and amprenavir are widely reported to be able to deactivate MP”, 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 a-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 play a significant role in the assembly of the viral genome. This protcin is involved in se eral aspects of the virus life cycle, such as assembly, budding, ehvelope formation, and pathogenesis. E. protein’s ion channel activity is found in the transmembrane fegion 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 coronavitus proteins as well as host cell proteins. E-protein’s ion channel activity and the altération of coronavirus cell ion balance by E- for virus production but the effeet of E-protein ion channel activity sis remains elusive, protein is a necessary proces in virus pathogen: N-TERMINAL TRANSMEMBRANE C-TERMINAL, 7 2 7 w 7 o 7 MYSFVSEETGTLIVNSVLLFLAFVVFLLVTLAILTALRLCAYCCNIVNVSLVKPTVYVYSRVKNLNSSEGVPDLLY 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 stitvived. 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 ct 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 ate reduced the random motion of the human COVID-19 E protein in terms of inhibiting the function of the Page 9human “COVID-19 F-protein”. So far, our understanding about the mechanism of the F-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, similat 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 vitions and process the viral replication and transcription. ‘This is one of the important open reseatch 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:teanscription. 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. sans-cove 8. Virion release S Protein Ace cell Lsars-covzentry J cytoplasm oy Membrane Fusion &> 3. RNA release protein 4. Translation Ribosomes Viral RNA Fig: The schematic diagram of the mechanism of COVID-19 entry and viral RNA packing in the human cell The coronavirus spike (8) 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 (Le. trypsin and Page 10furin), in two sites located at the boundary between the $1 and $2 subunits (S1/S2 site). In a later stage happens the cleavage of the $2 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, ahd 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 fueleoeapsid protein. ‘A different two-step mechanism has been suggested and in this case the vition binds to a receptor on the target host cell surface through its S1 subunit and the Spikelis 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 strinded RNAV is fully released into the cytoplasm. There takes place the replication and transcriptio# 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, $ and E are synthesized ifthe 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 regult they coalesce within the ERGIC membrane in order to self embly 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. Page 11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 56 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 Shortness of Loss of speech breath/ Difficulty or mobility or Chest pain breathing confusion Sr @% Loss of Taste fj a cou > : ge ches soretivot EAP Headoke ne A LESS COMMON SYMPTOMS al a Arash on the skin Redon EYE viantes \7 eriscolouration GIS tated eves of fingers or toes Fig: WHO’s advice to the public on COVID-19 symptoms The | y of toes) The virus can also lead to pneumonia, respiratory failure, heatt problems, liver problems, septic shock, and death. s Common symptoms include: a rash on skin, red or itritated eyes, discoloration of fingers 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 Page 12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 ¢orona 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 duid, 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, whieh 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 €urrently ramp up production for. The probability of developing these symptoms depends on allot 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 HC. 0. “*G KS HO ‘OH 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, Page 13+ 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 ifindoors + 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. + Ifyou 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 Cotincil 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 Page 14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 tisk 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 tisk 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 @fiy 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 ate nearly 2 times higher if you are someone with cancer than a person without cancet. The only people who should not be offered the vaccine are those who may have a harmful reaction, suchas 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 ot after cancer treatment. Page 15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 fof'a pétiod of time, but that assumption needs to be backed by empirical evidence, and some studies suggest otherwise. There ate 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 spetifically,its spike protein. Antibodies then attach to the virus and prevent it fom attaching to the host éells, 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. ee lal) ig. 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 Page 16has come up with an innovation called Lung IQ. This innovation is a holistic Al-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 CY'8 scanners, It can help radiologists detect and quantify findings better in daily practice. Itis 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-BIRAQ) 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 fof the ability to reuse FDA approved/ preclinical trial drugs for the disease. In the literature, we fifid 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 shost time, the response of the scientific €ommunity is such that involve enormous efforts to develop a novel therapy and treatment, For example, Chloroquine and Hydroxychloroquine, old drugs, have been used to t malarial, cheumatoid arthritis, lupus and sun allergies for more than sixty years. The activity of hydroxychloroguine 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 autoimmuine 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 clevation 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 48h, but no further reduction observed at 72h. 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 we 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 assigned 1:1:1:1 ratio to receive ZMapp (a triple monoclonal antibody groups have faster rate of vital clearance than later groups. Remdesivis has been promised antivisal drug against RNA viruses, including SARS/MERS, in cultured cell, shice 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 poténtial agent to be used to combat coronaviruses, Unfortunately, it could not be help to bela patients during the 2019 outbreak in the Democratic Republic of the Congo. A coronavirus research at the university of Towa 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. Hq [7H HY LH H H HOH Fig: Structure of REGN-EB3 Page 18‘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, thinorthea, 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 afitiviral 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 lopinavis-ritonavir group and standard care group. ‘They found that lopinavis-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 gfoup. Such study has found that lopinavir-ritonavir does not scem to be effective for COVID-19 patients and thes has produced more side effects (Cao et al, 2020). In summary, the antiviral drugs, alone and in combinations 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 afniviral property against Zika and Ebola virus in vitro, Itcan 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 f6.18 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 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 87.1% in patients treated with hydroxychloroquine only, and 12.5% 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. azithromycin with 500 mg on day in the control Page 19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, drag design, and high«throughput)screening to identified two drugs of these compound are Ebselen and thiadiazolidinone-8 (IDZD-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 $ 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 zitonavir could improve the conditions of several COVID-19 patients at the Rajavithi Hospital in Bangkok. Based on the repost, Gromica et al., have utilized computational docking approath (o/analysed the effect of synergism of these drugs against the COVID-19 main protease. They fourid 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 eannot 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 hydroxychloroguine 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 FDY approved therapeutics or drugs have not helped to treat, cure or prevent COVID-19, oR HHH Fig: Structure of Chloroquine TUPAC nomenclature: (RS)-N’-(7-chloroquinolin-4-y1)- jethyL-pentane-1,4- diamine Wo AS Oh, fi S cr A Structure of Hydroxychloroquine TUPAC 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 county'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 regul ‘ors have come together to Page 21introduce low-cost diagnostics, develop therapeutics, and conduct research to create safe and cffective vaccines during the COVID-19 pandemic, However, these communities have faced several challenges during different stages including discovery, research and development, clinical tials, 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 Apsil 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 t 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-viteo 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 tesearch and development related to coronavirus. ILS is the fourth lab to set up such an in-vite6 euluute fatility 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 Page 23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 i 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 healthcate 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 'T 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 shating protocols. ‘They also discussed the importance of Page 24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 ptiyate — 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, ahd 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 €merging 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 @ the Chinese government to alert the world early and quickly supply diagnostic data, infection Statistics, and World Health Organization (WHO) access and Gi, 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 Jems at the national and global | expert scientific advice. Of course, politicians have to include other factors besides science in their cls are flawed and political leaders do not listen to highly 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 t0 harness the best scientific advice and take effective action. Positive examples include Singapore, Taiwan, Republic of Korea, Austria, and Germany. Medical experts have poifited to the importance of robust public health care systems, early diagnosis through early broad-based testing, et. 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 to2 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 CEPT)” and “support the launch of joint research projects...and the sharing of facilities.” Yet-ongoing disageeements 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 accelefating “tit for tat” between the leaders has been a self inflicted wound on both cotintries. 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 dey therapeutics, and potential vaccines. International cooperation with initiatives and funding on clopment of new diagnostics, 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 res ch 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 sight 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 Intetgovernmental 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 (SI) 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. 2007 PEACE PRIZE (©@ THE NOBFL FOUNDATION 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 coronavieus 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 acfoss 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, ete. Because Covid-19 was an infectious disease, all those who were infected were instructéd 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, Por 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 diffetent protocols for the protection of people, Page 28Bibliography The following sources have been referred to for the entirety of the project: Cover Page Picture: 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 Il Part A All chemistry Structures - ChEBI, PubCHEM, Opsin SARS-CoV-2 picture: https://www.who.int/health- topics/coronavirusi#tab=tab_1 https://www.who .int/emergencies/diseases/novel-coronavirus-2019/advice- for-public https://www.cancer.gov/about-cancet/coronavirus/coronavirus-cancer- patient-information NEW: Structure of corona https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196923/ https://www.narayanahealth.org/blog/cancer-patients-and-new-corona- virus/ https://www.cancer.net/blog/2022-09/coronavirus-and-covid-19-what- people-with-cancer:need-know https://www.nebi.nim.nih.gov/pmc/articles/PMC7 3681 17/#:~:text=The%20d evelopment%200f%20medical%20biotechnology, COVID%2D 19%207%2C8. https://carnegieindia.org/2021/04/23/role-of-biotechnology-in-india-s-fight- 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/ Elementary Picture of Coronavirus structure: https://www.nature.com/articles/s41565-020-0732-3 Picture of cancer: https://scitechdaily.com/cancer-breakthrough- unexpected-link-discovered-between-most-common-cancer-drivers/ https://www.youtube.com/watch?v=5DGwOJXSxqg http://www.cdfd.org.in/ https://www.sciencediplomacy.org/editorial/2020/response-covid-19- pandemic-catastrophic-failures-science-policy-interface Page 29Page 30