SARS-CoV-2 and COVID-19 _ Taxonomy, Genetics, Life Cycle, Pathophysiology, Treatment, Management and Vaccines.pdf

SARS-CoV-2 and COVID-19
-Corona virus
-SARS-CoV-2 and COVID-19 _ Taxonomy, Genetics, Life Cycle, Pathophysiology, Treatment, Management and Vaccines

1. SARS-CoV-2and COVID-19
A presentation by
Aloo Denish
(Biochemist; Microbiologist)
ChukaUniversity; CSI International Ltd
E-mail:[email protected]
‘‘... if you know your enemies and know yourself, you will not be imperiled in a
hundred battles.’’ Sun Tzu, The Art of War

2. 1.0 History -Did you Know?
In the past, the world has faced respiratory disease pandemics ;
•The 1918 H1N1 (Spanish flu) -50 million deaths worldwide
•The 1957 H2N2 (Asian flu) -1–4 million deaths worldwide
•The 1968 H3N2 (Hong Kong flu) -1–4 million deaths worldwide
•The 2005 H5N1 (Bird flu)
•The 2009 H1N1 (Swine flu)-151,700–575,400 deaths worldwide
•2001 to 2003 severe acute respiratory syndrome (SARS)
•2012 to 2015 Middle East respiratory syndrome (MERS)
•December 2019: Novel coronavirus 2019 (SARS-CoV-2) that causes
Covid-19 discovered in Wuhan city, Hubei Province, China

3. 2.0 Definition
Coronaviruses (CoVs) are enveloped, positive-sense, single-stranded
RNA viruses that belong to the subfamily Coronavirinae, family
Coronavirdiae, order Nidovirales.
There are four genera of CoVs, namely, Alphacoronavirus(αCoV),
Betacoronavirus(βCoV), Deltacoronavirus(δCoV), and
Gammacoronavirus(γCoV)
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is
the virus that causes COVID-19 (coronavirus disease 2019), the
respiratory illness responsible for the COVID-19
Coronavirus disease (COVID-19)is an infectious disease caused by the
SARS-CoV-2 virus.

4. 3.0 Taxonomy of SARS-CoV-2
(unranked):Virus
Realm:Riboviria
Kingdom: Orthornavirae
Phylum:Pisuviricota
Class:Pisoniviricetes
Order:Nidovirales
Family:Coronaviridae
Genus:Betacoronavirus
Subgenus:Sarbecovirus
Species:Severe acute respiratory syndrome–related coronavirus
Virus:Severe acute respiratory syndrome coronavirus 2

5. 3.1 Variants of SARS-CoV-2
•There are many thousands of variants of SARS-CoV-2, which can be grouped into
the much larger clades.
•The World Health Organization has currently (2021) declared four variants of
concern, with evidence of increased transmissibility and virulence, alongside
changes to antigenicity, which are as follows:
•Alpha: Lineage B.1.1.7 emerged in the United Kingdom in September 2020.
Notable mutations include N501Y and P681H. An E484K mutation in some
lineage B.1.1.7 virionshas been noted
•Beta: Lineage B.1.351 emerged in South Africa in May 2020. Notable mutations
include K417N, E484K and N501Y.
•Gamma: Lineage P.1 emerged in Brazil in November 2020. Notable mutations
also include K417N, E484K and N501Y.
•Delta: Lineage B.1.617.2 emerged in India in October 2020.
•Other variantsinclude Lambda (lineage C.37), Mu (lineage B.1.621), Epsilon
(lineages B.1.429, B.1.427, CAL.20C), Zeta (lineage P.2), Theta (lineage P.3), Eta
(lineage B.1.525), Iota (lineage B.1.526), Kappa (lineage B.1.617.1), e.t.c.

6. 4.0 Structure of SARS-CoV-2
•Spherical, enveloped, around 80–120 nm in diameter, with multiple
outwardly projected club-like homotrimeric, glycosylated S proteins
imparting them incredible appearance of a solar corona, prompting
their popular name, CoVs.
•Enclosed within the lipid bilayer envelope of the virionis helically
symmetrical nucleocapsidscomprising complex of +ssRNAand capsid
proteins.
•There are four important structural proteins—spike (S), membrane
(M), envelope (E), and nucleocapsid(N) proteins—that are encoded by
structural genes located within the region preceeding30 end of
genome.
•There are several non-structural and accessory proteins, which
together are responsible for the structural and functional aspects of
virus

8. 5.0 Genome Organization
•SARS-CoV-2 is a positive-sense single-stranded RNA (+ssRNA) virus, with a
single linear RNA segment.
•Genome size ranges from 26 to 32 kb and comprise 6–11 open reading frames
(ORFs) encoding 9680 amino acid polyproteins(Guoet al. 2020).
•Genome has highest composition of U (32.2%), followed by A (29.9%), and a
similar composition of G (19.6%) and C (18.3%). The nucleotide bias arises from
the mutation of guanines and cytosinesto adenosines and uracils, respectively.
•The first ORF (ORF1a and ORF1b) comprises approximately 67% of the genome
that encodes 16 non-structural proteins(nsps), whereas the remaining ORFs
encode for accessory proteinsand structural proteins.
•Accessory genes are interspersed between the structural genes and contain at
least nine ORFs for accessory proteins.
•Its genome lacks the hemagglutinin-esterase gene. However, it comprises two
flanking untranslated regions (UTRs) at 5′end of 265 and 3′end of 358
nucleotides.

11. 6.0 Description of Structural
Organization
Non-structural proteins
Structural Proteins
Accessory proteins

12. 6.1 Non-structural proteins
•The initial two-thirds of the RNA sequence encode the two main
transcriptional units, ORF1a and ORF1ab; these units encode two
polyproteins(PP1a and PP1ab, respectively).
•The pp1a non-structural protein corresponds to NSP1 to NSP11
and pp1ab non-structural protein comprises of NSP12 to NSP16
•The larger unit, PP1ab, contains ORFs for at least 16 non-structural
proteins (Nsp1−16)
•The non-structural proteins have various functions in biological
phenomena that are important for the virus such as replication,
correction of replication errors (‘‘proofreading’’), translation,
suppression of host proteins, immune response blockage, and RNA
stabilization.

14. S.NoNameProtein (Full Name) and function
1 nsp1N-terminal productof the viralreplicase->acts as host translation inhibitor and also degradehost mRNAs
2 nsp2N-terminal product ->Binds to prohibitin1 and prohibitin2 (PHB1 and PHB2)
3 nsp3Papain-likeproteinase ->Responsible for release of NSP1, NSP2, and NSP3 from the N-terminal region of
pp1a and 1ab
4 nsp4Membrane-spanningprotein containingTransmembranedomain 2 ->Involves in double-membrane vesicle
formation
5 nsp5Proteinase and mainproteinase ->Inhibits IFNsignaling
6 nsp6Putativetransmembranedomain ->Induces formation of ER-derived autophagosomes
7 nsp7RNA-dependentRNA polymerase -Acts as a cofactor with nsp8 and nsp12
8 nsp8MultimericRNApolymerase; replicasesingle-stranded ->Makes heterodimer with NSP8 and12
9 nsp9RNA-binding viralprotein ->Involves in dimerization and RNA binding
10 nsp10Growth-factor-likeprotein possessingtwo zinc bindingmotifs ->acts as a scaffold protein for nsp14 and nsp16
11 nsp11short peptide at the end of orf1a -> Unclear function
12 nsp12RNA-dependent RNA polymerase –>forreplication and methylation
13 nsp13Helicase ->Helicase core domain binds ATP.Zinc-binding domain is involved in replication andtranscription
14 nsp14Exoribonucleasedomain(ExoN/nsp14) ->Exoribonucleaseactivity and N7-guanine methyltransferaseactivity
15 nsp15EndoRNAse;nsp15-A1 andnsp15B-NendoU -> Mn(2 + )-dependent endoribonucleaseactivity
16 nsp162’-O-MT: 2’-O-ribose methyltransferase ->mediates mRNA cap 20-O-ribose methylation

15. 6.2 Structural Proteins
•The structural genes encode the structural proteins, spike (S), envelope
(E), membrane (M), and nucleocapsid(N).
6.2.1 The S protein
•The total length of SARS-CoV-2 S is 1273 aaand consists of a signal peptide (amino acids 1–
13) located at the N-terminus, the S1 subunit (14–685 residues), and the S2 subunit (686–1273
residues)
•The S1 subunit and S2 subunit are responsible for receptor bindingand membrane fusion,
respectively.
•The S1 subunit comprises an N-terminal domain (14–305 residues) and a receptor-binding
domain (RBD, 319–541 residues).
•The S2 subunit comprises the fusion peptide (FP) (788–806 residues), heptapeptiderepeat
sequence 1 (HR1) (912–984 residues), HR2 (1163–1213 residues), TM domain (1213–1237
residues), and cytoplasm domain (1237–1273 residues).
•SARS-CoV-2 S harbors a furincleavage site (682–685 residues) at the S1/S2 boundary, which
may increase the efficiency of SARS-CoV-2 transmission

17. 6.2.2 Envelope (E) protein
•The smallest amongst all the structural proteins, around 8–12 kDa.
Function: plays major role in pathogenesis, virus assembly, and release .
6.2.3 Membrane (M) protein
•n is O-linked glycoprotein of around 25–30 kDa, and is most abundant amongst various
structural proteins, and possesses three distinct transmembranedomains .
•The homodimericM protein associates with other viral structural proteins, including
nucleocapsid, facilitating the molecular assembly of virus particles as well as may be
involved during pathogenesis.
6.2.4 Nucleocapsid(N) protein
•It distinctly possesses three highly conserved domains; an N-terminal domain, an RNA-
binding domain or a linker region, and a C-terminal domain.
•It has been observed that these three domains may together orchestrate RNA binding
and its phosphorylated status is prerequisite for triggering a structural dynamism
facilitating the affinity for viral versus non-viral RNA .
•Participates in RNA packaging in a beads-on-a-string type conformation. In addition to
be involved in organization of viral genome, N protein also facilitates virionassembly and
enhances virus transcription efficiency amongst others

18. 6.3 Accessory Factors
•There are nine accessory proteins—ORF3a, 3d, 6, 7a, 7b, 8, 9b, 14, and
10—produced from at least five ORFs encoding accessory genes
(ORF3a, ORF6, ORF7a, ORF7b, and ORF8), novel overlapping ORF3d
(earlier known as 3b), leaky scanning of sgRNAof N gene (ORF9b and
14), and ORF10 from downstream of N gene.
•Accessory proteins play a crucial role in virus replication
•They may also be involved in host immune escape.
•these proteins play an important role in interactions between the
virus and host, including modulating and blocking the production of
pro-inflammatory cytokines

19. 6.3.1 ORF3a and ORF3d Proteins
•Accessory factor 3a is encoded by ORF3a located in between the S
and E genes, and is the largest accessory proteins of SARS-CoV-2,
consisting of 274 amino acid residues.
•ORF3a forms dimer and its six transmembranehelices together create
ion channelinthe host cell membrane, which is highly conducive for
Ca2+/K+ cationscompared to Na+ ion. It is also involved in virus
release, apoptosis and pathogenesis.
•ORF3d encodes 3d protein which consists of 154-aa long
polypeptide chain, and is found to be located in the nucleolus
and mitochondria.
6.3.2 ORF6 Protein
•A61-amino acid long membrane-associated protein.

20. 6.3.3 ORF7a and ORF7b Proteins
•Synthesized from the bicistronicsubgenomicRNA 7 of SARS-CoV-2.
•The 122-aa ORF7a protein is a type-I transmembraneprotein
containing a 15 aasignal peptide sequence, an 81aa luminal domain,
21aa transmembranedomain and a short C-terminal tail.
•The ORF7b protein consists of 44-amino acids, and is an integral
membrane protein, expressed in SARS-CoV-infected cells wherein it
remains localized in the Golgi compartment
6.3.4 ORF8 Protein
•Consists of 121 amino acid residues.
•Has been found to interact with major histocompatibility complex-I
(MHC-I), thereby mediating their degradation in cell culture, and
therefore may help in immune evasion

21. 6.3.5 ORF9b Protein
•Consists of 97 amino acid residues, and is probably expressed by
leaky scanning of sgRNAof N gene.
•Tends to associate with adaptor protein, TOM70, and therby
suppress IFN-I mediated antiviral response
6.3.6 ORF10 Protein
•Encoding by gene predicted to be located downstream of the N
gene
6.3.7 ORF14 Protein
•Made up of 73 amino acid residues, and is also likely to be
synthesized by leaky scanning of sgRNAof N gene. However,
its function is not clearly understood.

22. 7.0 Mutations
•Mutation on the spike protein -Mutation 23403A>G-(D614G)
•Mutation on the NSP12 protein -Mutation 14408C>T-(P323L)
•Mutation on the ORF3a protein -Mutation 25563G>T-(Q57H)
•Mutation on the NSP2 protein -mutation 1059C>T-(T85I)
•Mutations on the NSP13 protein –
•Mutations on the ORF8 protein -two high-frequency
mutations, 28144T>C-(L84S) and 27964C>T-(S24L)
•Mutations on the nucleocapsidprotein -high frequency
mutations, 28881G>A, 28881G>A, and 28883G>C.

23. 8.0Life Cycle of SARS-CoV-2
•Involves cellular invasion of virus, expression of viral
genes, and formation of progeny and eventual exit.
•Involves :
Attachment to Host Cell Surface, Penetration and
Uncoating
Replication-Transcription Complex(RTC) Formation
Synthesis of Viral RNA
Molecular Assembly and Release of SARS-CoV-2

26. 8.1 Attachment to Host Cell Surface,
Penetration and Uncoating.
•The spike (S) protein, via its receptor binding domain (RBD), 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 S protein is subjected to proteolyticcleavages by host proteases
(i.e. trypsin and furin), in two sites located at the boundary between
the S1 and S2 subunits (S1/S2 site).
•In a later stage happens the cleavage of the S2 domain (S2′site) in
order to release the fusion peptide. This event will trigger the
activation of the membrane fusion mechanism. Typically, human cell
ingests the virus in a process called endocytosis

27. •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 cathepsinL proteolysis through intracellular
proteases and further activation of membrane fusion mechanism within
endosomes (Simmons et al., 2005).
•Then, the endosome opens to release virus to the cytoplasm, and
uncoatingof viral nucleocapsid(N) is started via proteasomes which
typically can hydrolyseendogenous proteins, but they are also capable of
degrading exogenous proteins such as the SARS nucleocapsidprotein (Q.
Wang et al., 2010).
•A different two-step mechanism has been suggested (Li, 2016) and in this
case the virionbinds to a receptor on the target host cell surface through its
S1 subunit and the Spike is cleaved by host proteases (Hasanet al., 2020)
and then it is expected the fusion at low pH between viral and host target
membranes via S2 subunit.
•Finally, the viral genetic material a single stranded RNA is fully released
into the cytoplasm.

28. 8.2 Replication-Transcription Complex(RTC)
Formation
•Immediately after release of viral nucleocapsid, +ssRNAserves as
functional mRNA with respect to ORF1a and ORF1b encoding
polyproteinpp1a (440–500 kDa) and pp1ab (740–810 kDa),
respectively.
•pp1a is 1.2–2.2 folds more expressed compared to pp1ab dueto
differential efficiency of frameshiftbetween ORF1a and ORF1b
genes.
•These two polyproteinsundergo autoproteolyticprocessing
yielding 16 nsps, which together form the RTC for viral RNA
synthesis.
•This functional RTC results into formation of a nested set of
sgRNAsvia discontinuous transcription.

29. 8.3 Synthesis of Viral RNA
•The formation of RTC sets molecular process in motion
leading to synthesis of multiple copies of viral RNA.
•These -ssRNA(negative ssRNA) serves as intermediate
template.
•Meanwhile, polymerase switches template at short motifs,
transcription regulated sequences (TRS) during -ssRNA
synthesis, thereby producing a multiple 50-nested set of
negative sense sgRNAswhich, in turn, used as templates to
form a 30-nested set of positive sense sgRNAs.
•Thereafter, they associate with host ribosome, synthesizing
various structural and accessory proteins building multiple
virus structure .

30. 8.4 Molecular Assembly and Release of SARS-CoV-2
•Most of the structural and accessory proteins associated with membrane such as
S, M, and E are synthesized by endoplasmic reticulum-bound ribosomes, whereas
other viral proteins, including N protein, are translated by free cytosolic
ribosomes of host cells.
•In addition, these structural proteins also undergo posttranslational modification
that modulate their functions.
•The assembly of virionconverges at site of endoplasmic reticulum–Golgi
intermediate compartment (ERGIC), wherein M protein provides scaffold and
orchestrate virionmorphogenesis by heterotypic interaction with other structural
proteins, such as M-S and M-E, thereby facilitating molecular incorporation.
•Furthermore, M-N interactions mediates condensation of the nucleocapsidwith
the envelope along with E protein.
•Post molecular assembly, progeny virionsare transported in smoothwallvesicle
and using secretory pathway they are trafficked to plasma membrane and
eventually exit though exocytosis and spread to other parts of body

31. 9.0 Transmission
Covid-19 is a contagious viral infection that can be spread through inhalation or
ingestion of viral respiratory droplets as a result of;
●Coughing ●Sneezing
●Talking/singing ●Sharing airspace 30 minutes infects
●Touching infected surfaces are primary sources of infection.
Silent spreaders of Covid-19
•Asymptomaticpatients: carry active virus in their body but never develop any
symptoms.
•Pauci-symptomatic(Mild) patients: Feel a little unwell from covid-19 infection but
continue to come into close contact with others.
•Pre-symptomaticpatients: Infected and are incubating the virus but no symptoms.
•Children: are not immune from this infection and their symptoms don’t correlate
with exposure and infection.

32. 10.0 PATHOPHYSIOLOGY
10.1 Asymptomatic Phase
•The inhaled virus SARS-CoV-2 binds to epithelial cells in the nasal
cavity via angiotensin converting enzyme 2 (ACE2).
•In vitro data with SARS-CoVindicate that the ciliated cells are
primary cells infected in the conducting airways.
•The virus undergoes local replication and propagation, along with the
infection of ciliated cells in the conducting airways.
•This stage lasts a couple of days and the innate immune response
generated during this phase is a limited one.
•In spite of having a low viral load at this time, the individuals are
highly infectious and the virus can be detected via nasal swab testing.

33. 10.2 Invasion and Infection of the Upper
Respiratory Tract
•The virus propagates and migrates from the nasal epithelium to the upper respiratory
tract via the conducting airways and a more robust innate immune response is triggered.
•Nasal swabs or sputum should yield the virus (SARS-CoV-2) as well as early markers of
the innate immune response.
•Due to the involvement of the upper airways, the disease manifests with symptoms of
fever, malaise and dry cough.
•There is a greater immune response during this phase involving the release of C-X-C
motif chemokine ligand 10 (CXCL-10) and interferons(IFN-β and IFN-λ) from the virus-
infected cells.
•The majority of patients do not progress beyond this phase as the mounted immune
response is sufficient to contain the spread of infection. For about 80% of the infected
patients, the disease will be mild and mostly restricted to the upper and conducting
airways. These individuals may be monitored at home with conservative symptomatic
therapy.

34. 10.3 Involvement Of The Lower Respiratory Tract And
Progression To Acute Respiratory Distress Syndrome (ARDS)
-Hypoxia, ground glass infiltrates/opacity and progression to ARDS
•About 20% of all infected patients progress to this stage of disease and develop severe
symptoms.
•The virus invades and enters the type 2 alveolar epithelial cells via the host receptor ACE-
2 and starts to undergo replication to produce more viral Nucleocapsids.
•The virus-laden pneumocytesnow release many different cytokines and inflammatory
markers such as interleukins (IL-1, IL-6, IL-8, IL-120 and IL-12), tumournecrosis factor-
α(TNF-α), IFN-λ and IFN-β, CXCL-10, monocyte chemoattractantprotein-1 (MCP-1) and
macrophage inflammatory protein-1α (MIP-1α).
•This ‘cytokine storm’ acts as a chemoattractantfor neutrophils, CD4 helper T cells and
CD8 cytotoxic T cells, which then begin to get sequestered in the lung tissue. These cells
are responsible for fighting off the virus, but in doing so are responsible for the
subsequent inflammation and lung injury.
•The host cell undergoes apoptosis with the release of new viral particles, which then
infect the adjacent type 2 alveolar epithelial cells in the same manner.
•Due to the persistent injury caused by the sequestered inflammatory cells and viral
replication leading to loss of both type 1 and type 2 pneumocytes, there is diffuse
alveolar damage eventually culminating in an acute respiratory distress syndrome

35. 11.0 Symptoms of COVID-19
COVID-19 affects different people in different ways. Most infected people will
develop mild to moderate illness and recover without hospitalization.
Most common symptoms:
●Fever ●cough ●Tiredness ●loss of taste or smell.
Less common symptoms:
●sore throat ●headache ●aches and pains ●diarrhoea
●a rash on skin, or discolourationof fingers or toes ●red or irritated eyes.
Serious symptoms:
●difficulty breathing or shortness of breath
●loss of speech or mobility, or confusion ●chest pain.
On average it takes 5–6 days from when someone is infected with the virus for
symptoms to show, however it can take up to 14 days.

37. 11.1 Covid-19 complications
●Acute respiratory failure (ARF) ●Acute respiratory distress syndrome (ARDS)
●Acute liver injury ●Septic shock
●Acute kidney injury ●Rhabdomyolysis
●Acute cardiac injury ●Acute brain injury
●Pneumonia & pulmonary embolism followed by extra-pulmonary systemic
hyperinflammationsyndrome.
●Adipose tissue: increased fat composition & sustained fat loss in recovered
patients, elevated plasma F.As and TAGs (hyperlipidemia).
A●cutePancreas injury: contribute to long-lasting diabetes. Insulin resistance,
hyperglycemia, altered glucose metabolism & development of T2D.
●Disseminated intravascular coagulation/blood clots; hypertension.
●Secondary infections: Strep and Staph that raises the risk of death.
●Multisystem inflammatory syndrome in children (MIS-C)

38. 12.0 COVID-19 Diagnosis
•Clinical features e.gfever, fatigue, Dry cough,
breathlessness etc
•Screening Laboratory Tests –hematologic, biochemical
inflammatory biomarkers etc.
•Imaging–chest x-ray, CT scan
•Molecular Examination –RT-PCR, Quantitative RT-PCR etc.
•Immunological Assays –ELISA, CLIA, IFA etc.
•Novel Techniques-Next generation sequencing, CRISPR,
LAMP etc.

41. 13.0 Treatment
•To date, no single medication has been reported or proposed
to combat the infective viral load of SARS-CoV-2.
•However, previous strategies for developing proper
medications to pulverize SARS-CoVcan be extrapolated to
COVID-19 infection effectively.
•Scientists, several research groups, and clinicians across the
globe are working towards finding effective medications that
can curtail or eliminate the viral load of SARS-CoV-2.
Below is a list of natural products/isolated compounds or
their derivatives and drugs that inhibit the coronavirus
family:

42. CategoriesCompound Name
Proposed Mode of Actions
Involved Viruses
Antiviral
drugs
Remdesivir( GS-5734,
Nucleoside analogue of
Remdesivirtriphosphate) ( RDV-TP )
Inhibitor of RdRp SARS-CoV-2
Lopinavir/Ritonavir
HIV protease
inhibitor
HIV infection,
SARS-CoV-1, and
MERS-CoV
Darunavir/Cobicistat Protease inhibitor
SARS-CoV-2
Favipiravir(T-705) Purine
nucleotide
RNA polymerase
inhibitor
RNA viruses and
SARS-CoV-2
Ribavirin (Guanine analogue)
Inhibits viral RdRp
SARS-CoV-1 and
SARS-CoV-2
Umifenovir(Arbidol)
Targeting the S
protein/ACE2 and inhibits
the membrane fusion of the
envelope of the virus
Influenza and
SARS-CoV-2

43. Antimalarial
drugs
Chloroquine( Synthetic
version of quinine and is
found in the bark of
cinchona trees)
Reduces the
rate of
replication
Malaria,
systemic
inflammatory
diseases, and
SARS-CoV-2
Hydroxychloroquine
Inhibition of glycosylation of
host receptors, proteolytic
processing, and acidification
of endosomes
SARS-CoV-2
and
autoimmune
diseases
Antiparasitic
drugs
Ivermectin
Inhibits nuclear
transport
Parasitic Infections
and SARS-CoV-2
Nitazoxanide(Anti-
helminthic drug)
Unclear
MERS and SARS-
CoV-2

44. Adjunctive
drugs
Corticosteroids/quinolone (n
combination) Prevents ARDS
SARS-CoV and
SARS-CoV-2
Monoclonal Antibodies
(Tocilizumab, Sarilumab,
Eculizumab, Fingolimod,
Bevacizumab)
Immunomodulatoryeffect,
inhibition of terminal
complement, and anti–VEGF
medication
SARS-CoV-2 and
Chronic
Inflammatory
disorders
ACE-Inhibitors and ARBs
( enzyme )
Activates RAAS
mechanism
SARS-CoV-2
Interferon-(α and β) Unclear
MERS-CoV and
SARS-CoV-2
Vitamin-D (Adjunct with
vitamin C and zinc)
Inhibits inflammatory
response and attenuates
cytokine storm
SARS-CoV-2

45. 13.1 Management of Patients with Confirmed
COVID-19
Check these two links for detailed explanation on
Management of Patients with Confirmed COVID-19
•https://www.health.go.ke/wp-
content/uploads/2020/06/Updated-Case-Management-
Guidelines-26_03_20-1.pdf
•https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-
guidance-management-patients.html

46. 14.0 Vaccines
There are four categories of vaccines in clinical trials:
Whole Virus Vaccines-use a weakened (attenuated) or deactivated form of the
pathogen that causes a disease to trigger protective immunity to it.
Nucleic Acid Vaccines-use genetic material (DNA or RNA) from a disease-
causing virus or bacterium (a pathogen) to stimulate an immune response against it
Viral Vector Vaccines-use a modified virus (the vector) to deliver genetic code
for antigen into human cells, thus infecting cells and instructing them to make large
amounts of antigen, which then trigger an immune response.
Protein Subunit Vaccines-use fragments of protein from the disease-causing
virus to trigger protective immunity against it.
Below is a list of authorized/approved vaccines against SARS-CoV-2 for
COVID-19 ($ FDA Approved, Emergency Use Authorization (EUA)
vaccines):

47. S/No
Vaccine
Name
Vaccine
Type
Developers
Country
of Origin
Current Schedule
andRoute of
Administration
Reported
Effectiveness
FollowingClinical
Trial
1.
Comirnaty
(formerly
BNT162b2)
mRNA-based
vaccine(encode
s mutated form
of
S protein)
Pfizer,
BioNTech;
Fosun
Pharma
Multinati
onal
Two doses, 21
days apart,
intramuscular
injection
95% efficacy in Phase
3
clinical trial
(NCT04368728).
92% efficacy in
vaccinated
healthcare workers .
2
Moderna
COVID-19
Vaccine
$
( mRNA -1273)
mRNA-
based
vaccine
Moderna,
BARDA,
NIAID
USA
Two doses, 28 days
apart, intramuscular
injection
94.1% efficacy in
Phase
3 clinical trial
(NCT04470427) .
3
COVID-19
Vaccine Janssen
(JNJ-78436735;
Ad26. COV2.S)
$
Non-
replicating
viral vector
Janssen
vaccines
(Johnsons &
Johnsons)
The
Netherla
nds, US
Single dose
vaccine,
intramuscular
injection
85% efficacy in
Phase 3
ENSEMBLE trial
(NCT04505722).

48. 4
COVID-19
Vaccine
AstraZenec
a
(Covishield)
Adenovirus
vaccine
BARDA,
OWS
UK
Two doses,
between
4–12 weeks
apart,
intramuscular
injection
79% efficacy in
Phase 3clinical trial
(NCT04516746).
100% efficacy in
severe disease
and
hospitalization
patients.
5
Sputnik V
(Gam-
COVIDVac)
Recombinant
adenovirus
vaccine ( rAd
26 and rAd5)
Gamaleya
Research Institute,
AcellenaContract
Drug Research
and development
Russia
Two doses, 21
days apart,
intramuscular
injection
94.1% efficacy
in Phase3
clinical trial
(NCT04530396)
6
CoronaVac
(formerly
PiCoVacc)
Inactivated
vaccine (
formalin with
alum adjuvant)
SinovacChina
Two doses,
between
14–18 days apart,
intramuscular
50% efficacy in
Phase 3
clinical trial
(NCT04456595) .

49. 7 BBIBP-CorV
Inactivated
SARS-CoV-
2 vaccine
(Vero cell)
Beijing Institute
of Biological
Products; China
National
Pharmaceutical
Group
(Sinopharm)
China
Two doses,
intramuscular
injection
86% efficiency Phase 3
clinical trial
( ChiCTR2000034780).
High effectiveness in
terms of neutralizing
antibody production in
rhesus macaques.
8 EpiVacCorona
Peptide
vaccine
Federal
Budgetary
Research
Institution State
Research Center
of Virology and
Biotechnology
Russia
Two doses,
21–28 days
apart,
intramuscular
injection
Phase1/2 trial
(NCT04527575)
Trial is still going
and evaluation
regarding
efficiency being
carried out.
9
Convidicea
(Ad5-nCoV)
Recombinant
vaccine
(adenovirus type
5 vector)
CanSino
Biologics
China
Single dose vaccine,
but also evaluated in
trial with 2-doses,
intramuscular
65.7% efficiency in
Phase 3 clinical
trial
(NCT04526990).

50. 10Covaxin
Inactivated
vaccine
Bharat Biotech in
collaboration
with National
Institute of
Virology), ICMR.
India
Two doses,
intradermally
81% in Interim
phase 3 trial
11
Name is
yet to be
specified
Inactivated
vaccine
Sinopharmand the Wuhan
Institute of
Virology under the Chinese
Academy of
Sciences China
Final number of
doses and
interval not yet
decided
Phase1/2 clinical trial
(ChiCTR2000031809) is
completed and 72.51 %
efficacy in on-going
phase 3 clinical trial.
12CoviVac
Inactivated
vaccine
Chumakov
Federal Scientific
Center for
Research and
Development of immune
and
Biological
Products
Russia
Not yet
finally
decided
Phase1/2
trial is
undergoing
13ZF2001
Recombinan
t vaccine
(CHO)
Anhui Zhifei
Longcom
Biopharma
ceutical, Institute of
Microbiology of the
Chinese
Academy of
Sciences
China,
Uzbekistan
Not yet finally
decided,
intramuscular
injection
Phase 3 clinical
trial
(NCT04646590) is
being evaluated.

51. 15.0 Control/Prevention
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 metreapart from others, even if they don’t appear to be sick.
•Wear a properly fitted mask when physical distancing is not possible or when in
poorly ventilated settings.
•Choose open, well-ventilated spaces over closed ones. Open a window if indoors.
•Wash your hands regularly with soap and water or clean them with alcohol-based
hand rub.
•Cover your mouth and nose when coughing or sneezing.
•If you feel unwell, stay home and self-isolate until you recover.

52. 16.0 Comparison of SARS-CoV2, SARS-
CoV, and MERS-Co

54. 17. References
1)https://www.who.int/emergencies/diseases/novel-coronavirus-2019
2)https://www.afro.who.int/health-topics/coronavirus-covid-19
3)https://en.wikipedia.org/w/index.php?title=Severe_acute_respirator
y_syndrome_coronavirus_2&oldid=1045920399
4)https://doi.org/10.1016/j.cell.2020.04.013
5). Romano M, Ruggiero A, SquegliaF, MagaG, BerisioR. A Structural
View of SARS-CoV-2 RNA Replication Machinery: RNA Synthesis,
Proofreading and Final Capping. Cells. 2020;9:1267.
6)S. Raskin, Genetics of COVID-19, Jornalde Pediatria,
https://doi.org/10.1016/j.jped.2020.09.002
7)Nanotechnology for Environmental Engineering (2021) 6:19.
https://doi.org/10.1007/s41204-021-00109-0

55. 7)Yadav, R.; Chaudhary, J.K.; Jain, N.; Chaudhary, P.K.; Khanra, S.; Dhamija, P.;
Sharma, A.; Kumar, A.; Handu, S. Role of Structural and Non-Structural Proteins
and Therapeutic Targets of SARS-CoV-2 for COVID-19. Cells 2021, 10, 821.
https://doi.org/10.3390/cells 10040821
8)https://doi.org/10.1371/journal.ppat.1008536.g003
9)Jha, N.K.; Jeyaraman, M.; Rachamalla, M.; Ojha, S.; Dua, K.; Chellappan, D.K.;
Muthu, S.; Sharma, A.; Jha, S.K.; Jain, R.; et al. Current Understanding of Novel
Coronavirus: Molecular Pathogenesis, Diagnosis, and Treatment Approaches.
Immuno2021, 1, 30–66. https://doi.org/ 10.3390/immuno1010004
10)https://en.wikipedia.org/w/index.php?title=Special:CiteThisPage&page=Influen
za_pandemic&id=1042124779&wpFormIdentifier=titleform
11)https://upload.wikimedia.org/wikipedia/commons/thumb/b/b4/Symptoms_of_
coronavirus_disease_2019_3.0.svg/800px-
Symptoms_of_coronavirus_disease_2019_3.0.svg.png
12)J Gene Med. 2021;23:e3303. https://doi.org/10.1002/jgm.3303
13)Audio: https://youtu.be/Q2MmREArTds

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