The document summarizes information about coronaviruses and COVID-19. It discusses that coronaviruses are small RNA viruses that infect humans and other animals. Seven human coronaviruses have been identified so far, including SARS-CoV-2 which causes COVID-19. COVID-19 spreads mainly from person to person and causes respiratory illness. While most cases are mild, some can progress to acute respiratory distress. There is currently no approved vaccine but many are in development worldwide using approaches like viral vectors and protein subunits.

1. Covid 19 Coronavirus
Sarvjeet SharmaPatliputra University

2. Coronavirusesareminute in size (65–125 nm in diameter) and contain a single-
stranded (+) RNA, size ranging from 26 to 32kbs in length

3. A brief overview of coronavirus
 A total of 39 species belong to the family family
Coronaviridae, sub family Cornidovirineae and order
Nidovirales (Gorbalenya et.,al 2020)
 Most of the species are enzootic
 Currently, seven human CoVs (HCoVs) have
been confirmed. (Schoeman and Fielding,2019)

4. Human coronavirus NL63 (HCoV-NL63)
Human coronavirus 229E (HCoV-229E)(mild resp.infection)
alpha-coronavirus genus
Human coronavirus OC43 (HCoV-OC43)
Human coronavirus (HCoV-HKU1) SARS-CoV, SARS-CoV-2
and Middle East respiratory syndrome coronavirus (MERS-
CoV)
beta-coronavirus genus
The SARS-CoV-2 (the subgenus Sarbecovirus) and mostly
resembles a bat coronavirus, shareing 96.2% sequence
homology( Chan et.,al 2020)
Currently, it is thought that SARS-CoV-2 has been
introduced to human by an unidentified intermediary animal
and then it has spread from human-to-human.

6. Coronavirus disease (COVID-19) outbreak
situation(WHO) Last update: 11 May 2020
. Countries, areas or territories with cases 215
 Confirmed cases 4 006 257
 Confirmed deaths 278 892

7. Salient features
 Health Organization (WHO) declared a pandemic on March 11, 2020.
 The outbreak of emerging severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) disease in China has brought globe at halt.
 The sudden emergence
 Exact origin is a mystery.
 Probably originated in a nonhuman host, most likely bats, amplified in palm
civets, and was transmitted to humans in live animal markets
 Consumption of infected animal is the major cause of animal to human
transmission of the virus and due to close contact with an infected person,
the virus is further transmitted to healthy persons.
.
 As no specific therapeutics and vaccines are available for disease control,
 Great threat for global public health.

9. Transmission

13. Transmision of SARScov2

14. Transmission human to human

15. Unique features
 Coronaviruses exhibit a high frequency of mutation during each
round of replication, including the generation of a high incidence of
deletion mutations.
 Coronaviruses undergo a high frequency of recombination during
replication; this is unusual for an RNA virus with a nonsegmented
genome
 May contribute to the evolution of new virus strains
 Similar to SARScov1
 Human airway trypsin-like protease (HAT), cathepsins and
transmembrane protease serine 2 (TMPRSS2) that split the spike
protein and establish further penetration changes

17. human airwaytrypsin-like protease (HAT), cathepsins and
transmembraneproteaseserine 2 (TMPRSS2) that split the spike protein
and establish further penetration changes

18. Structure and binding of COVID-19 virus to ACE2

19. human airwaytrypsin-like protease (HAT), cathepsins and transmembrane
protease serine 2 (TMPRSS2) that split the spike protein and establish
further penetration changes

21. Disease and pathogenesis

23. 5% -intensive critical care
15%-critical care
80% ambulatory care

24. Symptomsand pathogenesis

28.  Stage I (mild)—earlyinfection
 Includes an incubationperiod associatedwith
mild and often non-specificsymptoms, such as
malaise, fever, and a dry cough.
 SARS-CoV-2 multiplies and establishesresidence
in the host, primarilyon the respiratory system.
 binds to its target using the angiotensin-
converting enzyme 2 receptor on human cells,
abundantlypresent on human lung and small
intestineepitheliumand the vascular
endothelium.

29. Diagnosis includes
respiratory sample RT-PCR,
serum testing for SARS-CoV-2 IgG and IgM,
chest imaging, complete blood count, and liver
function tests.
Complete blood count may reveal a
lymphopenia and neutrophilia without other
significant abnormalities.
Treatment symptomatic relief.

30. Stage II (moderate)—with/without
hypoxia
 establishedpulmonarydisease,
 viral multiplicationand localized inflammationin the lung
 Treatmentsupportivemeasures and availableanti-viraltherapiessuch
as remdesivir

31. Stage III (severe)—systemic hyperinflammation
 Results in a decrease in Th, Th suppressor, and T regulatory cell
counts.
 inflammatory cytokines and biomarkers such as IL-2, IL-6, IL-7,
granulocyte colony-stimulating factor, macrophage inflammatory
protein 1-α, tumor necrosis factor-α, C-reactive protein, ferritin, and
D-dimer are significantly elevated in those patients with more
severe disease.
 Troponin and N-terminal pro B-type natriuretic peptide can also be
elevated.

 At last shock, vasoplegia, respiratory failure, and even
cardiopulmonary collapse are discernable. Systemic organ
involvement, even myocarditis

32. . Primary inflammatoryresponses occur early after viral infection, prior to the
appearanceof neutralizingantibodies(NAb). These responses are mainly driven by
active viral replication,viral-mediatedACE2 downregulation and shedding, and host
anti-viralresponses..
Secondary inflammatory responses begin with the generation of adaptive
immunity and NAb. The virus-NAb complex can also trigger FcR-mediated
inflammatory responsesand acute lung injury

33. Cytokine pathogenesis of coronavirus disease 2019 .

34.  use of cytokine inhibitors such as tocilizumab (IL-6
inhibitor) or anakinra (IL-1 receptor antagonist).
 Intravenous immune globulin may also play a role in
modulating an immune system that is in a
hyperinflammatory state.
 Overall, the prognosis and recovery from this critical
stage of the illness are poor

35. Prevention and Vaccine
development

Being the virus is novel, therefore humans have no natural
immunity to it,
 So need to start from square one to develop a vaccine to
educate the immune system against the virus.
 currently no vaccine or antiviral drug with proven efficacy
against SARS-CoV-2
Around 100 companies including indian biopharma :Bharat
Biotech and Serum institute are currently in development
worldwide,.
Volunteers— more than 14,000 have already signed up.
The scientists identified 29 viral genes corresponding to 29
proteins that human proteins interact with. “,

36. Essential tasks
 1.cultivation: difficult to grow. Presently humam
airway epithelial cell culture for vaccine
development
2. Antiviral research: to test the ability of existing or
experimental antivirals to treat or prevent infection
3. Pathogenesis research: to determine the various ways the
virus can be transmitted to a host, the severity of illness it
causes in a host, how much virus is produced in the body, and
what organs the virus can spread to within the body.
 4.Virus stability research: how long the virus can
remain viable and infectious on surfaces, and the
temperatures.

37. Bottlenecks
 Lack of in-depthknowledgeabout how the newlyemergedvirus
interactswith human cells
 Early-stagedatasuggestsabout unwanted immune responses. whatis
called “disease enhancement,” wherethe immune systemrespondsin
an unusual way, which can cause the illnessto be worse Thereare more
than two dozen companies working on coronavirus vaccines that are
already in early-stagetesting
 Typically, it takes 10 to 15 years of deliberateand careful work to
developa commercial vaccine—andas both the common cold and HIV
have demonstrated
 The most likely timelinesbest—12 to 18 months fora viable vaccine
againstSARS-CoV-2,

38. Viral components as vaccine
candidate

41. Major vaccines in trial

Viral-vectorvaccines:( Johnson & Johnson is
working)
 Nucleic-acidvaccines
 Protein-based vaccines:

42. Sinovac Biotech in Beijing with serum intitute India
Codagenix in Farmingdale, New York, with
the Serum Institute of India

46. Anticovid19 drugs
 Coronavirus puts science to the test
 “COVID-19 is a scientific challenge—how to stop
29,905 RNA bases in a lipid, protein, and sugar shell
from entering and replicating in our
 .

47.  Anti-malaria drug chloroquine
 Arthritis drugs IL6 inhibitors
 Ebola drug remdesivir
 Japanese flu pill favipiravir
 Combination of HIV drugs lopinavir and ritonavir, as
well as a combination of the latter two drugs infused with
Interferon beta
 ciclesonide, an inhaled corticosteroid used to treat
asthma and allergic rhinitismay represent as a potent drug
with dual roles [of antiviral and anti-inflammatory]
 anticancer drug called PB28. 20 times more potent
than hydroxychloroquine

49. Key epidemiological parameters
,
 incubationperiod of COVID-19, the basic reproductionnumber of
COVID-19 infection•
 Clinical presentationof COVID-19 infectionand course of associated
disease •
 Risk factors for transmissionand infection, and identificationof
possibleroutes of transmission
 Impact of infectionpreventionandcontrol measures in health care
settings
 Serological responsefollowingsymptomaticCOVID-19 infection
 Age-stratifiedseroprevalenceof antibodiesagainstCOVID-19 virus
 Cumulativeincidenceof infection, including extentof age-specific
infection
 Infection anddisease-severityratios(case-hospitalizationratio[CHR]
and case-fatalityratio[CFR])
 Viral load and shedding profiles
 Viral persistenceon surfaces

50. VIRAL-VECTOR VACCINES
 Around 25 groups are working. A virus such as measles
or adenovirus is geneticallyengineered so that it can
produce coronavirus proteins in the body.
 These viruses are weakened so they cannot cause
disease.
 There are two types:
 Replicating viral vector (such as weakened measles)
The newlyapproved Ebolavaccine is an exampleof a
viral-vector vaccine that replicates within cells
 Non-replicating viral vector (such as adenovirus) US-
based drug giant Johnson & Johnson is working

52. THANKS