University of traditional medicine

General medicine
Microbiology

Topic: coronavirus
Name: Jemima Guttiganti
Group: 202
Structure
• At their core, coronaviruses contain a genetic blueprint called RNA (beige), similar to DNA. The single-stranded RNA acts as a molecular message that enables production
of proteins needed for other elements of the virus.
• Bound to this string of RNA are nucleoproteins— (dark blue discs)—proteins that help give the virus its structure and enable it to replicate
• Encapsulating the RNA genome is the viral envelope (teal), which protects the virus when it is outside of a host cell. This outer envelope is made from a layer of lipids, a
waxy barrier containing fat molecules. As well as protecting the precious genetic cargo, this layer anchors the different structural proteins needed by the virus to infect cells.
• Envelope proteins (dark blue dots) embedded in this layer aid the assembly of new virus particles once it has infected a cell.
• The bulbous projections seen on the outside of the coronavirus are spike proteins (red-orange). This fringe of proteins gives the virus its crown-like appearance under the
microscope, from which the Latin name corona is derived. The spike proteins act as grappling hooks that allow the virus to latch onto host cells and crack them open for
infection. Like all viruses, coronaviruses are unable to thrive and reproduce outside of a living host
Replication cycle of coronavirus
• Virions bind to specific receptor glycoproteins or glycans via the spike protein.
• Penetration and uncoating occur by S protein-mediated fusion of the viral envelope with the plasma membrane or endosomal membranes. Gene 1 of viral genomic RNA is
translated into a polyprotein, which is processed to yield the transcriptase–replicase complex.
• Genomic RNA is used as a template to synthesize negative-stranded RNAs, which are used to synthesize full-length genomic RNA and subgenomic mRNAs.
• Each mRNA is translated to yield only the protein encoded by the 5′ end of the mRNA, including nonstructural proteins.
• The N protein and newly synthesized genomic RNA assemble to form helical nucleocapsids.
• Membrane glycoprotein M is inserted in the endoplasmic reticulum (ER) and anchored in the Golgi apparatus.
• Nucleocapsid (N plus genomic RNA) binds to M protein at the budding compartment (ERGIC).

• E and M proteins interact to trigger the budding of virions, enclosing the nucleocapsid.
• S and HE glycoproteins are glycosylated and trimerized, associate with M protein, and are incorporated into the maturing virus particles.
• Virions are released by exocytosis-like fusion of vesicles with the plasma membrane.
• Virions may remain adsorbed to the plasma membranes of infected cells.
• The entire cycle of coronavirus replication occurs in the cytoplasm.
Pathogenesis
• Coronaviruses have a high species-specificity and typically target
epithelial cells in the respiratory or gastrointestinal tract of animals.
• SARS coronavirus can infect epithelial cells in salivary gland ducts and
can spread to other organs, causing serious respiratory illness including
pneumonia and respiratory failure.
• The SARS virus likely originated in bats, amplified in palm civets, and
transmitted to humans in live animal markets.
• Chinese horseshoe bats are natural reservoirs of SARS-like
coronaviruses.Conditions in rural regions of southern China, where
outbreaks often begin, promote the emergence of new viral strains due
to close proximity of humans, pigs, domestic fowl, and the widespread
use of wild species for food and traditional medicine.
• Coronaviruses can cause gastroenteritis in humans.
• Animal models for enteric coronaviruses include porcine transmissible
gastroenteritis virus (TGEV), causing epithelial cell destruction and loss
of absorptive capacity.
• A novel porcine respiratory coronavirus (PRCV) emerged in Europe in
the 1980s, derived from TGEV by a large deletion in the S1
glycoprotein, causing widespread epizootics in pigs.
Clinical findings
• The human coronaviruses produce “colds,” usually afebrile, in adults. The symptoms are similar to those produced by
rhinoviruses, typified by nasal discharge and malaise.
• The incubation period is from 2 to 5 days, and symptoms usually last about 1 week. The lower respiratory tract is
seldom involved, although pneumonia in military recruits has been attributed to coronavirus infection.
• Asthmatic children may suffer wheezing attacks, and chronic pulmonary disease in adults may exacerbate respiratory
symptoms.
• The SARS coronavirus causes severe respiratory disease. The incubation period averages about 6 days. Common early
symptoms include fever, malaise, chills, headache, dizziness, cough, and sore throat, followed a few days later by
shortness of breath. Many patients have abnormal chest radiographs. Some cases progress rapidly to acute respiratory
distress, requiring ventilatory support. Death from progressive respi- ratory failure occurs in almost 10% of cases, with
the death rate highest among the elderly. SARS involves a cytokine storm, with elevated levels of multiple chemokines
and cyto- kines in the peripheral circulation for about 2 weeks.
• Clinical features of coronavirus-associated enteritis have not been clearly described. They appear to be similar to those
of rotavirus infections.
Immunity
• As with other respiratory viruses, immunity develops but is
not absolute. Immunity against the surface projection anti-
gen is probably most important for protection. Resistance to
reinfection may last several years, but reinfections with simi-
lar strains are common.
• Most patients (>95%) with SARS developed an antibody
response to viral antigens detectable by a fluorescent anti-
body test or enzyme-linked immunoassay (ELISA).
 Laboratory diagnosis
A. Antigen and Nucleic Acid Detection:
• ELISA test can detect coronavirus antigens in respiratory secretions if high-quality antiserum is available.
• Electron microscopy can be used to examine stool samples for enteric coronaviruses.
• Polymerase chain reaction (PCR) assays are useful for detecting coronavirus nucleic acid in respiratory secretions and stool samples.
• SARS virus RNA was detectable in plasma by PCR, with peak viremia between days 4 and 8 of infection.
B. Isolation and Identification of Virus:
• Isolating human coronaviruses in cell culture is challenging, but the SARS virus was successfully isolated from oropharyngeal
specimens using Vero monkey kidney cells.
C. Serology:
• Due to the difficulty of virus isolation, serodiagnosis using acute and convalescent sera is practical for confirming coronavirus
infections.
• ELISA, indirect immunofluorescent antibody assays, and hemagglutination tests can be used for serologic diagnosis.
• A passive hemagglutination test is used for serologic diagnosis of infections with strain 229E, where red cells coated with coronavirus
antigen are agglutinated by antibody-containing sera.
Epidemiology
• Coronaviruses are globally distributed and are a significant cause of respiratory illness, particularly during winter months.
• They cause 15–30% of all colds, with varying incidence from year to year (1% to 35% in one study).
• Antibodies to respiratory coronaviruses are common in adults, but antibodies to SARS coronavirus are uncommon.
• Coronaviruses commonly affect the elderly, with a frequency estimated to be about half that of rhinoviruses.
• SARS coronavirus can be airborne in healthcare settings and can contaminate surfaces.The SARS outbreak in 2002–2003
resulted in over 8000 cases in 29 countries, with a case fatality rate of 9.6%. Close contact with a SARS patient or recent
travel to an affected area was common among cases.
Treatment and prevention
• There is no proven treatment for coronavirus infections and no vaccine.
• Protease inhibitors used in the treatment of human immunodeficiency virus infections (eg, lopina- vir)
have in vitro activity against SARS coronavirus. SARS vaccines are under development.
• Control measures that were effective in stopping the spread of SARS included isolation of patients,
quarantine of those who had been exposed, and travel restrictions, as well as the use of gloves, gowns,
goggles, and respirators by health care workers.
Conclusion
• Coronaviruses are enveloped and contain a genome of single-stranded positive-sense RNA that is the largest genome among RNA viruses.
• Coronaviruses tend to be highly species-specific. How- ever, a novel coronavirus that originated in a nonhuman host caused a worldwide
outbreak of a severe acute respi- ratory syndrome (SARS) in 2003.
• Human coronaviruses typically cause common colds. SARS causes severe respiratory disease with a high mor- tality rate.
• Coronaviruses are distributed worldwide, with the exception of SARS virus.
• There is no proven treatment and no vaccine for coronaviruses.