ABSTRACT treatment. Though the vaccines are not yet
available,but can be made using genetic material of Coronavirus disease (COVID-19) is an infectious virus as like vaccine-derived poliovirus (VDPV), in disease caused by a newly discovered coronavirus. oral polio vaccine(OPV) contains an attenuated Most people infected with the COVID-19 virus will (weakened) vaccine-virus,activating an immune experience mild to moderate respiratory illness and response in body,so by using the concept we can recover without requiring special treatment. Older make an antidote of COVID-19 .An another way to people, and those with underlying medical problems stop COVID-19 in humans is increase the humoral like cardiovascular disease, diabetes, chronic immunity of humans by Supplements or any respiratory disease, and cancer are more likely to medicine,which resists against the virus. In short, develop serious illness. Coronavirus are the second reducing the activity of virus increasing the leading cause of the common cold (after strength of immunity. Or by reverse transcripting rhinoviruses) and until recent decades, rarely the genetic material of the virus as it contains single caused any disease more serious than a common stranded RNA as genetic material,by reverse cold in humans.The first coronavirus was isolated transcripting RNA and modifying it into double in 1937. Some cause illness in people and others stranded DNA,which will disable the activity of the circulate among other animals, including camels, virus .When this artificially modified DNA will cats and bats. Since its discovery, related comes in contact with the cells ,the golgi bodies of coronaviruses have been found to infect cattle, pigs, cell starts to replicate this DNA,so this can reduce horses, turkeys, cats, dogs, rats, and mice. The first or stop the activity of SARS-CoV-2. human coronavirus was cultured in the 1960s from nasal cavities of people with the common cold. The Keywords: CoronaVirus, Covid_19,SARS-CoV-2. new SARS-CoV-2 virus which is responsible for recent outbreak in Wuhan,China is also from Coronavirus family.As per most of reports uptil 1. INTRODUCTION now,this virus is transmitted to humans through Bats from Wuhan's raw meat market.World health SARS-CoV-2 is a new virus which belongs to the organization [WHO] has declared this,as pandemic coronavirus family. coronaviruses were only thought disease on 11 March 2020.Today many countries all to cause mild, self-limiting respiratory infections in over the world are facing this pandemic crisis and humans. Two of these human coronaviruses are α- researchers all across the world are trying to coronaviruses (HCoV-229E and HCoV-NL63) vaccine or antidote of it.Here we have given the while the other two are β-coronaviruses (HCoV- details of SARS-CoV-2 and idea of vaccination and OC43 and HCoV-HKU1). HCoV-229E and HCoV- OC43 were isolated nearly 50 years ago while of age. The outbreak began in a hotel in Hong Kong HCoV-NL63 and HCoV-HKU1 were only recently and ultimately spread to more than two dozen identified following the SARS-CoV outbreak . These countries. During the epidemic, closely related viruses are endemic in the human populations, viruses were isolated from several exotic animals causing 15–30% of respiratory tract infections each including Himalayan palm civets and raccoon dogs . year. They cause more severe disease in neonates, the However, it is widely accepted that SARS-CoV elderly, and in individuals with a greater incidence of originated in bats as a large number of Chinese lower respiratory tract infection in these populations. horseshoe bats contain sequences of SARS-related HCoV-NL63 is also associated with acute CoVs and contain serologic evidence for a prior laryngotracheitis (croup) . One interesting aspect of infection with a related CoV . In fact, two novel bat these viruses is their differences in tolerance to SARS-related CoVs were recently identified that are genetic variability. HCoV-229E isolates from around more similar to SARS-CoV than any other virus the world have only minimal sequence divergence identified to date . They were also found to use the while HCoV-OC43 isolates from the same location same receptor as the human virus, angiotensin but isolated in different years show significant converting enzyme 2 (ACE2), providing further genetic variability . This likely explains the inability evidence that SARS-CoV originated in bats. of HCoV-229E to cross the species barrier to infect Although some human individuals within wet animal mice while HCoV-OC43 and the closely related markets had serologic evidence of SARS-CoV bovine coronavirus, BCoV, are capable of infecting infection prior to the outbreak, these individuals had mice and several ruminant species. Based on the no apparent symptoms . Thus, it is likely that a ability of MHV to cause demyelinating disease, it has closely related virus circulated in the wet animal been suggested that human CoVs may be involved in markets for several years before a series of factors the development of multiple sclerosis (MS). facilitated its spread into the larger population. However, no evidence to date suggests that human CoVs play a significant role in MS. SARS-CoV primarily infects epithelial cells within the lung. The virus is capable of entering macrophages and dendritic cells but only leads to an abortive infection . Despite this, infection of these cell types may be important in inducing pro- inflammatory cytokines that may contribute to disease . In fact, many cytokines and chemokines are produced by these cell types and are elevated in the serum of SARS-CoV infected patients . The exact mechanism of lung injury and cause of severe disease in humans remains undetermined. Furthermore, Fig 1: 3D modelling of Coronavirus animals infected with rodent-adapted SARS-CoV strains show similar clinical features to the human 1.1. SARS-CoV disease, including an age-dependent increase in disease severity . These animals also show increased SARS-CoV, a group 2b β-coronavirus, was identified levels of proinflammatory cytokines and reduced T- as the causative agent of the Severe Acute cell responses, suggesting a possible Respiratory Syndrome (SARS) outbreak that immunopathological mechanism of disease . occurred in 2002–2003 in the Guangdong Province of China. It is the most severe disease caused by any 1.2. SARS-CoV-2 coronavirus. During the 2002–2003 outbreak approximately 8098 cases occurred with 774 deaths, Severe acute respiratory syndrome coronavirus 2 resulting in a mortality rate of 9%. This rate was (SARS-CoV-2),previously known by the provisional much higher in elderly individuals, with mortality name 2019 novel coronavirus (2019-nCoV), is a rates approaching 50% in individuals over 60 years positive-sense single-stranded RNA virus. It is contagious in humans and is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19) that has been designated a Public Health Emergency of International Concern by the World Health Organization [WHO]. SARS-CoV-2 has close genetic similarity to bat coronaviruses, from which it likely originated. An intermediate animal reservoir such as a pangolin is also thought to be involved in its introduction to humans. From a taxonomic perspective, SARS-CoV-2 is classified as a strain of the species severe acute respiratory syndrome-related coronavirus (SARSr-CoV). disease, lung disease and diabetes, for example — The strain was first discovered in Wuhan, China, so it seem to be at higher risk of developing serious has sometimes been referred to as the "Wuhan virus" COVID-19 illness.From a study ,it seems that people or "Wuhan coronavirus". Because the World Health with 45+ age group are at high risk . Organization discourages the use of names based upon locations and to avoid confusion with the disease SARS, it sometimes refers to the virus as "the virus responsible for COVID-19" or "the COVID-19 virus" in public health communications.
The SARS-CoV-2 virus is a betacoronavirus, like
MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats.Early on, many of the patients at the epicenter of the outbreak in Wuhan, Hubei Province, China had some link to a large seafood and live animal market, suggesting Graphical representation of risk factor in age groups. animal-to-person spread. Later, a growing number of patients reportedly did not have exposure to animal SARS-CoV-2 is an airborne disease and spreading markets, indicating person-to-person spread. Person- rapidly among all the countries of the world like to-person spread was subsequently reported outside forest fire,daily new cases are reported.Apart from Hubei and in countries outside China, including in this a relief news is that,although cure or treatment is the United States. Some international destinations not yet discovered,some patients are recovering now have ongoing community spread with the virus succesfully. that causes COVID-19, as do some parts of the United States. Community spread means some people have been infected and it is not known how or where they became exposed.
The complete clinical picture with regard to COVID-
19 is not fully known. Reported illnesses have ranged from very mild (including some with no reported symptoms) to severe, including illness resulting in death. While information so far suggests that most COVID-19 illness is mild, a report external icon out of China suggests serious illness occurs in 16% of No.of increasing cases and recovery and death cases cases. Older people and people of all ages with severe chronic medical conditions — like heart electron microscopy, is the protein responsible for allowing the virus to attach to the membrane of a host cell.
Fig 2 CoronaVirus Structure with RNA and protein
Spikes
Protein modeling experiments on the spike protein of
the virus soon suggested that SARS-CoV-2 has A report and graph by the World Health Organization [WHO],upto sufficient affinity to the angiotensin converting 25th March. enzyme 2 (ACE2) receptors of human cells to use 1.3. INFECTION THROUGH SARS- them as a mechanism of cell entry. By 22 January CoV-2. 2020, a group in China working with the full virus genome and a group in the United States using The exact origin of infection is not known but reverse genetics methods independently and according to previous reports,the infection was first experimentally demonstrated that ACE2 could act as transmitted from Bats to human and then human to the receptor for SARS-CoV-2. Studies have shown human. And Human-to-human transmission of that SARS-CoV-2 has a higher affinity to human SARS-CoV-2 has been confirmed during the 2019– ACE2 than the original SARS virus strain. SARS- 20 coronavirus pandemic. Transmission occurs CoV-2 may also use basigin to gain cell entry. primarily via respiratory droplets from coughs and Initial spike protein priming by transmembrane sneezes within a range of about 2 metres (6 ft 7 protease, serine 2 (TMPRSS2) is essential for entry in).Indirect contact via contaminated surfaces is of SARS-CoV-2. After a SARS-CoV-2 virion another possible cause of infection. Preliminary attaches to a target cell, the cell's protease TMPRSS2 research indicates that the virus may remain viable on cuts open the spike protein of the virus, exposing a plastic and steel for up to three days, but does not fusion peptide. The virion then releases RNA into the survive on cardboard for more than one day or on cell, forcing the cell to produce copies of the virus copper for more than four hours, and is inactivated by that are disseminated to infect more cells.[better soap.Viral RNA has also been found in stool samples source needed] SARS-CoV-2 produces at least three from infected people. virulence factors that promote shedding of new 1.4. UNCOATING THE VIRUS virions from host cells and inhibit immune response.
Each SARS-CoV-2 virion is approximately 50–
200 nanometres in diameter.Like other coronaviruses, SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins; the N protein holds the RNA genome, and the S, E, and M proteins together create the viral envelope. The spike protein, which has been imaged at the atomic level using cryogenic Fig.3 Corona Population under lungs cells genome.
The new SARS-CoV-2 sequence was compared to
existing genomes using online NCBI BLAST 1.5. Coronavirus Replicate Protein (https://blast.ncbi.nlm.nih.gov/Blast.cgi). Expression and Processing The final genome of sequenced SARS-CoV-2 The proteinase activities for all coronaviruses include consists of a single, positive-stranded RNA that is both papain-like proteinase (PLP) and picornavirus 29,811 nucleotides long, broken down as follows: 3C-like proteinase activities that are encoded within 8,903 (29.86%) adenosines, 5,482 (18.39%) the replicase polyproteins and mediate both cis and cytosines, 5,852 (19.63%) guanines, and 9,574 trans cleavage events (Ziebuhr et al., 2000). Because (32.12%) thymines. of the parallel evolution of the proteinases, their cleavage sites, and the hierarchical cleavage The sequence of BetaCoV/Nepal/61/2020 from processes, the proteolytic processing of the coordinates 1 to 29811 is identical to the sequence of coronavirus replicase proteins may serve as distinct isolate Wuhan-Hu-1 (GenBank accession number regulatory and genetic elements (Ziebuhr et al., NC_045512) from 16 to 29826 (29810/29811), 2001). Specifically, there are both conserved and except at site 24019, with the same substitution of a divergent regions of the replicase polyproteins by C from isolate Wuhan-Hu-1 for T. amino acid identity and similarity, with the sequences The C24019T mutation corresponds to C24034T if and predicted mature proteins beginning with the 3C- we use the sequence located under GISAID strain like proteinases through the carboxy terminus of the identifier EPI_ISL_405839 as a reference. This was a replicase polyprotein retaining higher identity and silent mutation at the spike gene (codon AAC to similarity across the predicted proteins. In contrast, AAT). Based on the reference sequence, the the amino-terminal third of the replicase following five mutations were also identified: demonstrates the most variation in proteins, cleavage T8782C (in ORF1a, codons AGT to AGC, silent site locations, and the number of proteinases that mutation), T9561C (in ORF1a, codons TTA to TCA, mediate maturation processing. SCoV appears to non silent mutation), C15607T (in ORF1b, codons have the general organization of, and similar protein CTA to TTA, silent mutation), C28144T (in ORF8b, sizes to, the group 2 coronaviruses such as MHV in codons TCA to TTA, non silent mutation), and this part of the genome (Snijder et al., 2003). T29095C (in nucleocapsid, codons TTT to TTC, However, SCoV likely uses only one PLP to mediate silent mutation). the cleavages, similar to the group 3 coronavirus infectious bronchitis virus (IBV). Thus this region of 1.7. Data availability. the replicase may experience the most variability, suggesting either the encoding of accessory functions This sequence has been deposited in GenBank under that are flexible and tolerant of changes, or the accession number MT072688 and at the GISAID conversely group or host-specific roles that are EpiCoV newly emerging coronavirus SARS-CoV-2 subject to pressure for more rapid change. platform under identifier EPI_ISL_410301. The accession numbers for the Illumina MiSeq sequence 1.6. Genetic seqeuencing raw reads in the NCBI Sequence Read Archive The new virus responsible for COVID-19 has (SRA) are PRJNA608651 (BioProject), genomic sequence of 29,811 bp with no gap and high average coverage (>77,000×). Primer binding sites at the 5′ and 3′ ends were removed, resulting in this genome being 59 nucleotides (nt) shorter than a reference genome in GenBank (accession number NC_045512), excluding the poly(A) tail of the Fig 4. 20,2020). Genome SARS-CoV can be efficiently grown in cell Code of culture and rapidly spread from person to person . It can survive in feces and urine at room temperature for >2 days (http://www.who.int/csr/sars/en) and may cause serious, even fatal, disease. SARS- CoV, a National Institute of Allergy and Infectious Diseases Biodefense Category C CoronaVirus priority pathogen (http://www2.niaid.nih.gov/Biodefense/band Data taken from ASM journal.”Complete Genome c_priority.htm) could be used by Sequence of a 2019 Novel Coronavirus (SARS- bioterrorists as a biological weapon. CoV-2) Strain Isolated in Nepal” Therefore, development of effective and safe vaccines is urgently needed to prevent a new SARS epidemic and for biodefense 2. REVIEW LITERATURE preparedness. As COVID-19 is a new outbreak,obviously Currently, 3 major classes of SARS vaccines we don’t have any treatment or cure uptil are under development: now. Researchers all over the world are 1) inactivated SARS-CoV working on getting the solution to this. we’ll 2) full-length S protein look to the reference for the general idea for 3) those based on fragments containing antidote or vaccine , maybe it will not be neutralizing epitopes . enough for it but it can be the beginning of Another way is the prevention from it.From the past research ,which have done disease.Though we don’t know the cure ,but on vaccination for viral disease or anti-viral prevention we know. Many countries all vaccines,it has seen that curcumin present in over the world has announced the lockdown turmeric have antiviral properties,for like including India ,USA, Russia,and etc.and HIV, HCV ,HBV and etc. peoples are strictly advised to follow the (reference:HIV,Sui et al.1993, Mazumder et quarantine .Patients affected with al.1995,Barthelemy et al.1998. COVID-19 are kept in isolation and given HCV:Anggakusuma et al.2014. HBV:Wei et proper care.Increase rate in new cases and al.2017,kim et al.2009,2011.) Curcumin’s death rate is the matter of concern but world antiviral properties are yet not discovered health organizations [WHO] and for COVID-19, but it can be effective if governments ,medical staff and research is conducted on it.(reference: Lisa services,researchers and investigators all kirchoff et al.2019) over the world are trying their best. In Medical Terms,the concept of viral infections are related and dependent on immunogenicity."Knowing the immunogenicity of certain viral regions, or in other words, which parts of the virus the immune system reacts to and how strongly, is of immediate relevance for the design of promising vaccine candidates and their evaluation," explained principal Investigator Alessandro Sette, Dr Biol Sci (reference:kenneth bender et al.March 3. IDEAS OF TREATMENT coronaviruses faces many challenges . First, for mucosal infections, natural infection does not prevent Currently, there are no antiviral therapeutics that subsequent infection, and so vaccines must either specifically target human coronaviruses, so induce better immunity than the original virus or treatments are only supportive. In vitro, interferons must at least lessen the disease incurred during a (IFNs) are only partially effective against secondary infection. Second, the propensity of the coronaviruses . IFNs in combination with ribavirin viruses to recombine may pose a problem by may have increased activity in vitro when compared rendering the vaccine useless and potentially to IFNs alone against some coronaviruses; however, increasing the evolution and diversity of the virus in the effectiveness of this combination requires further the wild . Finally, it has been shown in Fractional evaluation . The SARS and MERS outbreaks have dose of inactivated poliovirus [ FIPV] that stimulated research on these viruses and this research vaccination with S protein leads to enhanced disease . has identified a large number of suitable anti-viral Despite this, several strategies are being developed targets, such as viral proteases, polymerases, and for vaccine development to reduce the likelihood of entry proteins. Significant work remains, however, to recombination, for instance by making large deletions develop drugs that target these processes and are able in the nsp1 or E proteins , rearranging the 3" end of to inhibit viral replication. the genome , modifying the TRS sequences , or using mutant viruses with abnormally high mutation rates We have only limited options for coronavirus. that significantly attenuate the virus . Vaccines have only been approved for IBV, TGEV, and Canine CoV, but these vaccines are not always As we know,that SARS-CoV 2 affects the human used because they are either not very effective, or in respiratory system,which is directly related to lungs some cases have been reported to be involved in the and pulmonary body parts,due to which the patients selection of novel pathogenic CoVs via suffering from disease faces problem in breathing and recombination of circulating strains. Vaccines for other respiratory functions.Though the vaccines are veterinary pathogens, such as Porcine epidemic not yet available,but can be made using genetic diarrhea virus [PEDV], may be useful in such cases material of virus as like vaccine-derived poliovirus where spread of the virus to a new location could (VDPV), in oral polio vaccine(OPV) contains an lead to severe losses of veterinary animals. In the attenuated (weakened) vaccine-virus,activating an case of SARS-CoV, several potential vaccines have immune response in body,like this the vaccine for been developed but none are yet approved for use. covid-19 can be made. These vaccines include recombinant attenuated viruses, live virus vectors, or individual viral proteins expressed from DNA plasmids. Therapeutic SARS- CoV neutralizing antibodies have been generated and could be retrieved and used again in the event of another SARS-CoV outbreak. Such antibodies would be most useful for protecting healthcare workers. In general, it is thought that live attenuated vaccines would be the most efficacious in targeting coronaviruses. This was illustrated in the case of Transmissible gastroenteritis virus [ TGEV], where Fig 6:Strategy for designing vaccines for severe acute an attenuated variant, Porcine respiratory coronavirus respiratory syndrome (SARS) using inactivated [ PRCV], appeared in Europe in the 1980s. This SARS-associated coronavirus. This virus expresses variant only caused mild disease and completely several structural proteins, including nucleocapsid protected swine from TGEV. Thus, this attenuated (N), membrane (M), envelope (E), and spike (S). virus has naturally prevented the reoccurrence of severe TGEV in Europe and the U.S. over the past 30 years . Despite this success, vaccine development for Another way to stop SARS-CoV in humans is tetracycline. increase the humoral immunity of humans by supplements or any medicine,which resists against 2.6. Another way of treatment is to maintain a the virus. In short, reducing the activity of viruses little higher temperature than normal room and increasing the strength of immunity. temperature,as the virus is less stable at high temperature and high humidity.Avoid using 3.1. The curcuminoids were detected as air conditioned places . curcumin, desmethoxy curcumin, and bisdesmethoxy curcumin,present in turmeric Owing to the lack of effective therapeutics or have anti inflammatory effects.Also vaccines, the best measures to control human turmeric contains curcumin oil,which have coronaviruses remain a strong public health antibacterial ,antiviral ,antimicrobial and surveillance system coupled with rapid diagnostic antifungal uses. testing and quarantine when necessary. For international outbreaks, cooperation of governmental 3.2. In ayurveda,turmeric is said to be a Golden entities, public health authorities and health care spice which can cure various diseases providers is critical. including common cold and pneumonia,so curcumin abstracts can be used to increase CONCLUSION immunal strength. The above study concludes the information of human 2.4 In traditional way vaccines,the genetic coronavirus and SARS-CoV-2 ,the past outbreak material from weakened virus is injected in history and ideas of treatment ,vaccination and the body so that the immunal cells recognize antidote. We hope it will help in discovering the ideal it and destroys it,and the other way is to cure or vaccine for COVID-19. 1)An ideal vaccine insert the modified genetic material into the should be able to deactivate the activities of viruses body ,so that the immunal cells produce that in the human body. 2)It should be able to provide the kind of molecule that destroys or disable the immunity strength to the cells of the body. virus.or by reverse transcripting the genetic 3)Currently many countries all the world have started material of the virus as it contains single their clinical trials of inactivated COVID -19 stranded RNA as genetic material,by reverse vaccines like USA,China and Russia .4) Recent transcripting RNA and modifying it into studies have demonstrated that recombinant RBD double stranded DNA,which will disable the consists of multiple conformational neutralizing activity of the virus .when this artificially epitopes that induce highly potent neutralizing modified DNA comes in contact with the antibodies against SARS-CoV (9,26,35–38). Unlike cells ,the golgi bodies of cell starts to full-length S protein, RBD does not contain replicate this DNA,so this can reduce or stop immunodominant sites that induce non neutralizing the activity of SARS-CoV-2. antibodies. RBD sequences are relatively conserved. Thus, recombinant RBD or vectors encoding RBD 2.5 Antidote can be made from the may be used as safe and efficacious vaccines for genetic material of animals who don't preventing infection by SARS-CoV with distinct get affected by SARS-CoV-2,or the genotypes. ones who have survived from SARS- CoV-2. REFERENCES
2.5. Patients of SARS-CoV-2 at pneumonial 1. Institute of Medicine (US) Forum on
stage can be treated with anti-pneumonial Microbial Threats; Knobler S, Mahmoud A, supplements like Macrolide Lemon S, et al., editors. antibiotics,Fluoroquinolones,Tetracyclines Washington (DC): National Academies groups medicines which include Press (US); 2004. ciprofloxacin,levofloxacin, doxycycline and 2. Mark R. Denison, M.D."CORONAVIRUS Morales, Runa Jha, Daniel K. W. Chu, RESEARCH:KEY TO DIAGNOSIS, Haogao Gu, Malik Peiris, Anup Bastola, Bibek TREATMENT AND PREVENTION OF Kumar Lal, Hemant Chanda Ojha, Ali A. SARS.".2004 Rabaan, Lysien I. Zambrano, Anthony 3. Mayo Foundation for Medical Education Costello, Kouichi Morita, Basu Dev Pandey, and Research (MFMER)."Coronavirus Leo L. M. Poon.”Complete Genome Sequence disease 2019 (COVID-19)".2020 of a 2019 Novel Coronavirus (SARS-CoV-2) 4. "Coronavirus Disease 2019 (COVID-19)". Strain Isolated in Nepal.”American society for Centers for Disease Control and Prevention microbiology.March 2020. (CDC). 11 February 2020. 15. Shibo Jiang, * Yuxian He,* and Shuwen 5. "Coronavirus disease (COVID-19) Liu*”SARS Vaccine Development.”Emerging outbreak". World Health Organization infectious disease.July 2005. (WHO). 16. Dimas Praditya,1,2,3,† Lisa Kirchhoff,4,† 6. "SARS-CoV-2 (Severe acute respiratory Janina Brüning,1,† Heni Rachmawati,5,6 Joerg syndrome coronavirus 2) Sequences". National Center for Biotechnology Steinmann,4,7,* and Eike Steinmann1,*”Anti- Information (NCBI). infective Properties of the Golden Spice Curcumin”. frontier in microbiology.2019 7. "COVID-19 Resource Centre". The Lancet.
8. "2019-nCoV Data Portal". Virus Pathogen
17.Kenneth Bender “Study Team Identifies Database and Analysis Targets for COVID-19 Vaccine”. Contagions live. March 20,2020 9. Huang P (22 January 2020). "How Does Wuhan Coronavirus Compare with MERS, 17. SARS and the Common Cold?". NPR. Archived from the original on 2 February 18. 2020. Retrieved 3 February 2020. 19. 10. Shield C (7 February 2020). "Coronavirus: From bats to pangolins, how do viruses reach us?". Deutsche Welle. Retrieved 13 March 2020.
11. Rodney Rohde"2019 Novel Coronavirus
(2019-nCoV) Update: Uncoating the Virus".American society for microbiology.jan 31.2020
12. David A.J. Tyrrell and Steven H.
Myint."Medical Microbiology 4th edition".
13. Spaan W, Cavanagh D, Horzinek MC.
Coronaviruses: structure and genome expression. J Gen Virol. 1988;69:2939.