Covid-19 is an infectious disease caused by SARS-CoV-2. mechsnism, pathogenesis and causes, transmission,symptoms and therapeutic strategies Published by karuna raghuwanshi,M.pharma II semester (pharmaceutics),Pharmacy department.

1. NOVEL CORONAVIRUS (Covid-19)
A pandemic disease
Presented by karuna raghuwanshi
M.pharma || sem
Pharmaceutics

2. Content
• Introduction
• History and origin
• Transmission
• Features and structure of SARS-CoV-19
• Mechanism and replication
• Symptoms
• Diagnosis
• Avoidance
• Precaution
• Protection
• Myth
• Poetntial therapeutic strategies against covid-19
• Ongoing researches

3. INTRODUCTION
• The coronavirus disease 19 (COVID-19) Is a highly transmittable and
pathogenic viral infection caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2),which emerged in Wuhan,China and spread
around the world.Genomic analysis revealed that SARS-CoV-2 is
phylogenetically related to severe acute respiratory syndrome-like (SARS-
like) bat viruses, therefore bats could be the possible primary reservoir.
• This virus was reported to be a member of the β group of coronaviruses.
The novel virus was named as Wuhan coronavirus or 2019 novel
coronavirus (2019-nCov) by the Chinese researchers. The International
Committee on Taxonomy of Viruses (ICTV) named the virus as SARS-CoV-
2 and the disease as COVID-19 .

4. History and origin
• By the end of 2019,WHO was informed by the Chinese government about
several cases of pneumonia with unfamiliar etiology. The outbreak was
initiated from the Hunan seafood market in Wuhan city of China and rapidly
infected more than 50 people. The live animals are frequently sold at the
Hunan seafood market such as bats, frogs, birds, marmots and rabbits [10],
• Wuhan an emerging business hub of China experienced an outbreak of a
novel coronavirus that killed more than eighteen hundred and infected over
seventy thousand individuals within the first fifty days of the epidemic.
• On 12 January 2020,the National Health Commission of China released
further details about the epidemic, suggested viral pneumonia [10].Novel
corona virus (2019) infected 120,000 individuals with mortality rate of 2.9%,
across 109 countries till. However, the rapid human to human transfer has
been confirmed widely. The intermediate source of origin and transfer to
humans is not known.

5. Transmission
• The key reservoirs and mode of transmission of coronaviruses (suspected
reservoirs of SARS-CoV-2 are red encircled) only α and β coronaviruses
have the ability to infect humans.
• The consumption of infected animal as a source of food 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 person.
• The human to human spreading of the virus occurs due to close contact
with an infected person, exposed to coughing, sneezing,respiratory droplets
or aerosols. These aerosols can penetrate the human body (lungs) via
inhalation through the nose or mouth.

6. Graphical Representation

7. Features and structure of SARS-CoV-2
• Corona viruses belong to the Coronaviridae family in the Nidovirales order.
Corona represents crown-like spikes CoV-2 on the outer surface of the
virus; thus, it was named as a coronavirus.
• SARS-CoV-2 is an enveloped positive-sense single-stranded RNA virus
(ssRNA) consisting of 29,903 nucleotides and two untranslated sequences
of 254 and 229 nucleotides at the 5’- and 3’-ends, respectively (GenBank
No. MN908947).

8. Features and structure
• SARS-CoV-2 possesses the typical coronavirus structure with spike protein
and also expressed other polyproteins, nucleoproteins, and membrane
proteins, such as RNA polymerase, 3-chymotrypsin-like protease, papain-
like protease, helicase, glycoprotein, and accessory proteins.
• Corona viruses are minute in size (65–125 nm in diameter) and contain a
single-stranded RNA as a nucleic material,size ranging from 26 to 32kbs in
length.
• The subgroups of coronaviruses family are alpha (α),beta (β),gamma (γ)
and delta (δ) coronavirus. It shows that the transmission rate of SARS-
CoV-2 is higher than SRAS-CoV and the reason could be genetic
recombination event at S protein in the RBD region of SARS-CoV-2 may
have enhanced its transmission ability.
• The severe respiratory distress syndrome acute respiratory syndrome
coronavirus (SARS-CoV),H5N1 influenza A,H1N1 2009 and Middle East
respiratory syndrome coronavirus (MERS-CoV) cause acute lung injury
(ALI) and acute (ARDS) which leads to pulmonary failure and result in
fatality.

9. Mechanism and replication

10. Mechanism and replication
• The novel SARS-CoV-2 enters human cells via binding of the glycoprotien
spikes present on the outer surface of the coronavirus to the human
angiotensin converting enzyme 2 (ACE2).
• The spike protein of SARS-CoV-2 contains a 3-D structure in the RBD
region (receptor binding domain) to maintain the van der Waals forces .
• The 394 glutamine residue in the RBD region of SARS-CoV-2 is recognized
by the critical lysine 31 residue on the human ACE2 receptor.
• The RBD is loosely attached among virus,so the virus may infect multiple
hosts.
• The Spike glycoprotein of the Wuhan coronavirus is modified via
homologous recombination
• The spike glycoprotein of SARS-CoV-2 is the mixture of bat SARS-CoV
and a not known Beta-CoV.
• The single N501T mutation in SARS-CoV-2's Spike protein may have
significantly enhanced its binding affinity for ACE2.

11. The life cycle of SARS-CoV-2 in host
cells
The life cycle of SARS-CoV-2 in host cells

12. The life cycle of SARS-CoV-2 in host cells
• Its life cycle begins when S protein binds to the cellular receptor ACE2. After
receptor binding, the conformation change in the S protein facilitates viral envelope
fusion with the cell membrane through the endosomal pathway.
• Then SARS-CoV-2 releases RNA into the host cell. The Structural proteins are
encoded by the four structural genes, including spike (S), envelope (E), membrane
(M) and nucleocapsid (N) genes.
• The orf1ab is the largest gene in SARS-CoV-2 which encodes the pp1ab protein and
15 nsps. The orf1a gene encodes for pp1a protein which also contains 10 nsps .
• Genome RNA is translated into viral replicase polyproteins pp1a and 1ab, which are
then cleaved into small products by viral proteinases. The polymerase produces a
series of subgenomic mRNAs by discontinuous transcription and finally translated
into relevant viral proteins.
• Viral proteins and genome RNA are subsequently assembled into virions in the ER
and Golgi and then transported via vesicles and released out of the cell. ACE2,
angiotensin-converting enzyme 2; ER, endoplasmic reticulum; ERGIC, ER–Golgi
intermediate compartment.

13. Symptoms
• The signs and symptoms of COVID-19 are a bit similar to influenza and
seasonal allergies fever,Cough,shortness in breathing,,Headache.

14. Diagnosis
• From the sequence-based analysis of isolates from the patients,the virus
was identified as a novel corona virus. Moreover,the genetic sequence was
also provided for the diagnosis of viral infection
•
Avoiding
• Avoid Social gathering,Visiting market or public place unnecessarily.
• Avoid Smoke,tobacco,Cold drink and any type of food and chemicals that
causes cold and short breathing or allergic problems.
• Don’t touch face,eyes and nose without washing your hands

15. precaution
• Wash your hands at every 30 minute by soap or any disinfectant or
sanitizer.
• Maintain social distancing (atleast 1 meter) and Stay at home.
• Cover your face (mouth and nose) with mask and gloves used at the public
place and grocery shop then dispose it properly.
• Wash vegitables and hands properly after coming your home,Follow good
respiratory hygiene. Take care of people with suspected or confirmed
covid-19.
• Do all banking activities online if posiible.

16. Boost immune system
• Take healthy and balanced diet to improve immune system.
• Use pepper longum (pippali),black pepper (kali mirch),dry ginger
(shunthi))and tulsi at regular basis in your food or in the form of decotion to
boost your immunity.

17. Protection from COVID 19-
• If you are unwell, even with mild symptoms, self isolate yourself and seek
medical care to reduce the risk of severe infection.
• An accurate and rapid diagnostic kit or meter use for detection of SARS-
CoV-2 in suspected patients is required. Keep in mind, everyone is at a risk
of getting covid-19.
• Older,adult and person of any age with pre-existing medical condition
appear at a high risk of serious illness than others.

18. Myth
• Viruses can not travel on radio waves or mobile network.
• Covid-19 is spread through respiratory droplets,sneezes or speaks and by
touching a contaminated surface or their eyes,nose and mouth.-19
• You can catch covid-19 in a very sunny and hot whether.
• Frequent or excessive alcohol can increase the risk of your health
problems.

19. POTENTIAL THERAPEUTIC STRATEGIES AGAINST
COVID-19
• There is no clinically approved antiviral drug or vaccine available to be used
against COVID-19.
• Drug repurposing against SARS-CoV-2 using pharmacophore based virtual
screening and molecular docking with main protease as the target
• The concept of drug repurposing (or repositioning) came into the spotlight
against covid-19.
• Few broad-spectrum antiviral drugs have been evaluated against COVID-
19 in clinical trials, resulted in clinical recovery,
• Initially –
• Interferons-α nebulization, broad-spectrum antibiotics, and anti-viral drugs
were used to reduce the viral load.
• hydroxychloroquine, an approved anti-malarial drug, and two known
antivirals, ritonavir and remdesivir, have been reported to be effective
against SARS-CoV-2 in vitro.

20. Potential therapeutic strategies
against covid-19
• Various other anti-virals are currently being evaluated such as -
Nafamostat
Nitazoxanide
Ribaviri
Penciclovir
Favipiravir
Ritonavir
AAK1
• These drugs exhibited moderate results when tested against infection in
patients and in- vitro clinical isolates.
• Combining the antiviral or antibiotics with traditional Chinese medicines
were also evaluated against SARS-CoV-2 induced infection in humans.

21. Potential therapeutic strategies
against covid-19
• In a recent study,it was identified that monoclonal antibody (CR3022)
binds with the spike RBD of SARS-CoV-2,because the antibody’s epitope
not overlapping with the divergent ACE2 receptor-binding motif.
• CR3022 has the potential to be developed as a therapeutic candidate,alone
or in combination with other neutralizing antibodies for the prevention and
treatment of COVID-19 infection.
Vaccines against SARS-CoV-2
• There is no available vaccine against COVID-19, while previous vaccines or
strategies used to develop a vaccine against SARS-CoV can be effective.
• Recently in Shanghai, doctors isolated the blood plasma from clinically
recovered patients of COVID-19 and injected it in the infected patients who
showed positive results with rapid recovery .

22. Vaccines against SARS-CoV-2
• The mRNA based vaccine prepared by the US National Institute of Allergy
and Infectious Diseases against SARS-CoV-2 is under phase 1 trial.
• INO-4800-DNA based vaccine will be soon available for human testing.
• (CDC) working on the development of an inactivated virus vaccine .
• Soon mRNA based vaccine’s sample (prepared by Stermirna Therapeutics)
will be available. Chinese Centre for Disease Control and Prevention.

23. Ongoing research
• Among the 4600 drugs screened 17 drugs were identified as candidate
inhibitors of the viral protease based on the glide scores obtained from
molecular docking.
• Binding free energy calculation showed that 6 drugs viz, Binifibrate,
Macimorelin acetate, Bamifylline, Rilmazafon, Afatinib and Ezetimibe can
act as potential inhibitors of the viral protease.
• Another dimension has been recently added by combining virtual drug
screening methods with
• machine learning approaches for the development of new drugs,
overcoming multidrug resistance , and applications in precision medicine to
select drugs for individualized therapies.

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