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The Most Recent Updates On CoVID-19
Done By:
Ali Mostafa Ali
Sara Salama Alganzoury
Under Supervision Of:
Dr. Mohamed M. Omran
Associated professor of Biochemistry Helwan university, Faculty of
science, chemistry department
Table of Contents
1.Genome of corona viruses
2.Comparative analysis of emergence
and spreading
3.Entry Mechanism
4. COVID-19 Case Study
5.Face mask Case Study
6.Pharmacologic Treatments for
Coronavirus Disease
Introduction to Corona Family
• Coronaviruses belong to the Coronaviridae family in the Nidovirales order.
Corona represents crown-like spikes on the outer surface of the virus; thus, it
was named as a coronavirus.
• Coronaviruses are minute in size (65-125nm in diameter) and contain a single-
stranded RNA as a nucleic material, of 26 to 32kbs in length.
• The subgroups of the family are alpha (α), beta (β), gamma (γ) and delta (δ)
coronavirus.
• The severe 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 respiratory distress
syndrome (ARDS) which leads to pulmonary failure and result in fatality
Corona Virus genome
Figure 1: Structure of respiratory syndrome causing human
94%
6%
Infected 1,506,420 Death 88,100
SARS-coV-2
2019 until now
74%
26%
Infected 2.428 Death 838
MERS-coV
2013
91%
9%
Infected 8,000 Death 776
SARS-coV
2003
China Saudi Arabia The whole World
Figure 2: Comparative analysis of emergence and spreading of
Structure Protein Function
Membrane Protein (M) • Central organizer of CoV
assembly
• Determine Shape of Viral
Protein
RNA • positive-strand RNA virus
with high homology to bat
coronavirus
Nucleocapsid Protein (N) • Bound to RNA genome to
make up nucleocapsid
Spike Protein (S) • Critical for binding of host
cell receptors to facilitate
entry of host cell
Envelope Protein (E) • Interacts with M to form
viral envelope
Figure 3: Structure of Corona
Key features and entry mechanism of human
coronaviruses
All coronaviruses contain specific genes in ORF1 downstream regions that
encode proteins for viral replication, nucleocapsid and spikes formation
1. The receptor-binding domain (RBD) is loosely attached among virus,
therefore, the virus may infect multiple hosts.
2. The entry mechanism of a coronavirus depends upon cellular proteases
which include, human airway trypsin-like protease (HAT), cathepsins
and transmembrane protease serine 2 (TMPRSS2) that split the spike
protein and establish further penetration changes
3. MERS-coronavirus employs dipeptidyl peptidase 4 (DPP4), while HCoV-
NL63 and SARS-coronavirus require angiotensin-converting enzyme 2
(ACE2) as a key receptor
Figure 4: The life cycle of SARS-CoV-2 in host cells
Mechanism of Infection
• Begins its life cycle 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. 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.
Mechanism of viral infection
Genomic variations in SARS-CoV-2
• The genome of the SARS-CoV-2 has been reported over 80% identical to the
previous human coronavirus (SARS-like bat CoV)
• 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
• Recent studies have indicated notable variations in SARS-CoV and SARS-CoV-2 such
as the absence of 8a protein and fluctuation in the number of amino acids in 8b and
3c protein in SARSCoV-2
• It is also reported that 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 .In a fluorescent study, it was confirmed that the SARS-CoV-2 also uses the same
ACE2 (angiotensin-converting enzyme 2) cell receptor and mechanism for the entry to host
cell which is previously used by the SARS-CoV.
• The single N501T mutation in SARS-CoV-2’s Spike protein may have significantly enhanced
its binding affinity for ACE2 .
Genomic variations in SARS-CoV-2
Figure 5: Beta coronaviruses genome organization
Comparative analysis of emergence and spreading of coronaviruses
• These viruses were thought to infect only animals until the world witnessed a severe acute
respiratory syndrome (SARS) outbreak caused by SARS-CoV, 2003 in Guangdong, China Fig
(2).
• The virus was confirmed as a member of the Beta-coronavirus subgroup and was named
SARS-CoV
• A decade later in 2012, a couple of Saudi Arabian nationals were diagnosed to be infected
with another coronavirus and named as the (MERS-CoV)
Coronavirus lingered in a woman's eyes long
after it cleared from her nose
• Italy's first confirmed COVID-19 patient had detectable levels of infectious viral
particles in her eyes, long after the infection had cleared from her nose, according to a
report of the case.
• On Jan. 23, a 65-year-old woman flew from Wuhan, China — where the coronavirus
outbreak first began — to Italy.
• Five days later, she began experiencing symptoms of COVID-19 and was admitted to
the hospital the following day. Her initial symptoms included a dry cough, sore throat,
coryza, or inflammation of the mucous membrane in the nose, and conjunctivitis, or
pink eye.
• She tested positive for the new coronavirus, SARS-CoV-2, and a few days later, she later
also developed a fever, nausea and vomiting.
• On the third day she was at the hospital, healthcare professionals took an eye swab
and discovered she had RNA, or genetic material, from the coronavirus in her eyes.
Cont.
• The healthcare professionals continued to take eye swabs daily. Though the woman's pink
eye cleared on the 20th day she was at the hospital, they found the virus lingered up to the
21st day, according to the report.
• For the next couple of days, the virus was undetectable in both the nose and the eyes. But
on day 27, they detected the virus once more in her eyes.
• "SARS-CoV-2 RNA was detected in ocular swabs days after it was undetectable in nasal
swabs," the authors wrote in the letter. What's more, using lab tests that amplify the viral
particles, the researchers confirmed that the sample of virus taken from her eyes was
replicating and thus could be viable.
Small Things Makes The Big Difference
• Transmission Characteristics of COVID-19
• A primary route of transmission of SARS-CoV-2 is likely via small droplets that are ejected when speaking,
coughing or sneezing. The most common droplet size threshold has a minimum at 5 μm to 10 μm
• Patients are most infectious during the initial days of infection (10–15), when symptoms are mildest or not
present. This characteristic differentiates SARS-CoV-2 (COVID-19) from SARS-CoV, as replication is activated
early in the upper respiratory tract
• Filtering Capability of Masks
• Masks can be made of different materials and designs which influence their filtering capability. There are
rigorous standards evaluating masks used in healthcare settings.
• One approach that has been studied for handling N95 or FFP2 respirator shortages is sterilization and re-use,
which can be effective.
Clothes Masks VS Surgical Masks
• Generally available household materials had between a 49% and 86% filtration
rate for 0.02 μm exhaled particles whereas surgical masks filtered 89% of those
particles.
• Particle sizes for speech are on the order of 1 μm.
• In a laboratory setting, household materials had 3% to 60% filtration rate for
particles in the relevant size range, finding them comparable to some surgical
masks
• In another laboratory setup, a tea cloth mask was found to filter 60% of particles
between 0.02 μm to 1 μm, where surgical masks filtered 75%
Pharmacologic Treatments for
Coronavirus Disease 2019
(COVID-19)
Fig 6: Simplified Representation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Lifecycle and Potential Drug Targets (Sanders
Table 1: Summary of Pharmacology for Select Proposed COVID-19 Treatments (Sanders et al., 2020)
Table 1 Cont. : Summary of Pharmacology for Select Proposed COVID-19 Treatments (Sanders et al., 2020)
• BCG vaccination prevents severe forms of tuberculosis in children and diversion of local
supplies may result in neonates not being vaccinated, resulting in an increase of disease
and deaths from tuberculosis.
• In the absence of evidence, WHO does not recommend BCG vaccination for the
prevention of COVID-19.
• WHO continues to recommend neonatal BCG vaccination in countries or settings with a
high incidence of tuberculosis.
BCG Vaccine, According to WHO
• Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus
Disease 2019 (COVID-19): A Review. JAMA. 2020 Apr 13.
• Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: Origin, transmission, and
characteristics of human coronaviruses. J Adv Res. 2020 16;24:91-98.
• Bacille Calmette-Guérin ( BCG ) vaccination and COVID-19. (2020). 36(April), 2019–2020. www.who.int/news-
room/commentaries.
• Kumar, M. (2020). The FDA-approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication
and attenuates inflammation in human cells.
References

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The Most Recent Updates On CoVID-19

  • 1. The Most Recent Updates On CoVID-19 Done By: Ali Mostafa Ali Sara Salama Alganzoury Under Supervision Of: Dr. Mohamed M. Omran Associated professor of Biochemistry Helwan university, Faculty of science, chemistry department
  • 2. Table of Contents 1.Genome of corona viruses 2.Comparative analysis of emergence and spreading 3.Entry Mechanism 4. COVID-19 Case Study 5.Face mask Case Study 6.Pharmacologic Treatments for Coronavirus Disease
  • 3. Introduction to Corona Family • Coronaviruses belong to the Coronaviridae family in the Nidovirales order. Corona represents crown-like spikes on the outer surface of the virus; thus, it was named as a coronavirus. • Coronaviruses are minute in size (65-125nm in diameter) and contain a single- stranded RNA as a nucleic material, of 26 to 32kbs in length. • The subgroups of the family are alpha (α), beta (β), gamma (γ) and delta (δ) coronavirus. • The severe 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 respiratory distress syndrome (ARDS) which leads to pulmonary failure and result in fatality
  • 4. Corona Virus genome Figure 1: Structure of respiratory syndrome causing human
  • 5. 94% 6% Infected 1,506,420 Death 88,100 SARS-coV-2 2019 until now 74% 26% Infected 2.428 Death 838 MERS-coV 2013 91% 9% Infected 8,000 Death 776 SARS-coV 2003 China Saudi Arabia The whole World Figure 2: Comparative analysis of emergence and spreading of
  • 6. Structure Protein Function Membrane Protein (M) • Central organizer of CoV assembly • Determine Shape of Viral Protein RNA • positive-strand RNA virus with high homology to bat coronavirus Nucleocapsid Protein (N) • Bound to RNA genome to make up nucleocapsid Spike Protein (S) • Critical for binding of host cell receptors to facilitate entry of host cell Envelope Protein (E) • Interacts with M to form viral envelope Figure 3: Structure of Corona
  • 7. Key features and entry mechanism of human coronaviruses All coronaviruses contain specific genes in ORF1 downstream regions that encode proteins for viral replication, nucleocapsid and spikes formation 1. The receptor-binding domain (RBD) is loosely attached among virus, therefore, the virus may infect multiple hosts. 2. The entry mechanism of a coronavirus depends upon cellular proteases which include, human airway trypsin-like protease (HAT), cathepsins and transmembrane protease serine 2 (TMPRSS2) that split the spike protein and establish further penetration changes 3. MERS-coronavirus employs dipeptidyl peptidase 4 (DPP4), while HCoV- NL63 and SARS-coronavirus require angiotensin-converting enzyme 2 (ACE2) as a key receptor
  • 8. Figure 4: The life cycle of SARS-CoV-2 in host cells Mechanism of Infection
  • 9. • Begins its life cycle 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. 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. Mechanism of viral infection
  • 10. Genomic variations in SARS-CoV-2 • The genome of the SARS-CoV-2 has been reported over 80% identical to the previous human coronavirus (SARS-like bat CoV) • 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 • Recent studies have indicated notable variations in SARS-CoV and SARS-CoV-2 such as the absence of 8a protein and fluctuation in the number of amino acids in 8b and 3c protein in SARSCoV-2
  • 11. • It is also reported that 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 .In a fluorescent study, it was confirmed that the SARS-CoV-2 also uses the same ACE2 (angiotensin-converting enzyme 2) cell receptor and mechanism for the entry to host cell which is previously used by the SARS-CoV. • The single N501T mutation in SARS-CoV-2’s Spike protein may have significantly enhanced its binding affinity for ACE2 . Genomic variations in SARS-CoV-2
  • 12. Figure 5: Beta coronaviruses genome organization
  • 13. Comparative analysis of emergence and spreading of coronaviruses • These viruses were thought to infect only animals until the world witnessed a severe acute respiratory syndrome (SARS) outbreak caused by SARS-CoV, 2003 in Guangdong, China Fig (2). • The virus was confirmed as a member of the Beta-coronavirus subgroup and was named SARS-CoV • A decade later in 2012, a couple of Saudi Arabian nationals were diagnosed to be infected with another coronavirus and named as the (MERS-CoV)
  • 14. Coronavirus lingered in a woman's eyes long after it cleared from her nose • Italy's first confirmed COVID-19 patient had detectable levels of infectious viral particles in her eyes, long after the infection had cleared from her nose, according to a report of the case. • On Jan. 23, a 65-year-old woman flew from Wuhan, China — where the coronavirus outbreak first began — to Italy. • Five days later, she began experiencing symptoms of COVID-19 and was admitted to the hospital the following day. Her initial symptoms included a dry cough, sore throat, coryza, or inflammation of the mucous membrane in the nose, and conjunctivitis, or pink eye. • She tested positive for the new coronavirus, SARS-CoV-2, and a few days later, she later also developed a fever, nausea and vomiting. • On the third day she was at the hospital, healthcare professionals took an eye swab and discovered she had RNA, or genetic material, from the coronavirus in her eyes.
  • 15. Cont. • The healthcare professionals continued to take eye swabs daily. Though the woman's pink eye cleared on the 20th day she was at the hospital, they found the virus lingered up to the 21st day, according to the report. • For the next couple of days, the virus was undetectable in both the nose and the eyes. But on day 27, they detected the virus once more in her eyes. • "SARS-CoV-2 RNA was detected in ocular swabs days after it was undetectable in nasal swabs," the authors wrote in the letter. What's more, using lab tests that amplify the viral particles, the researchers confirmed that the sample of virus taken from her eyes was replicating and thus could be viable.
  • 16. Small Things Makes The Big Difference • Transmission Characteristics of COVID-19 • A primary route of transmission of SARS-CoV-2 is likely via small droplets that are ejected when speaking, coughing or sneezing. The most common droplet size threshold has a minimum at 5 μm to 10 μm • Patients are most infectious during the initial days of infection (10–15), when symptoms are mildest or not present. This characteristic differentiates SARS-CoV-2 (COVID-19) from SARS-CoV, as replication is activated early in the upper respiratory tract • Filtering Capability of Masks • Masks can be made of different materials and designs which influence their filtering capability. There are rigorous standards evaluating masks used in healthcare settings. • One approach that has been studied for handling N95 or FFP2 respirator shortages is sterilization and re-use, which can be effective.
  • 17. Clothes Masks VS Surgical Masks • Generally available household materials had between a 49% and 86% filtration rate for 0.02 μm exhaled particles whereas surgical masks filtered 89% of those particles. • Particle sizes for speech are on the order of 1 μm. • In a laboratory setting, household materials had 3% to 60% filtration rate for particles in the relevant size range, finding them comparable to some surgical masks • In another laboratory setup, a tea cloth mask was found to filter 60% of particles between 0.02 μm to 1 μm, where surgical masks filtered 75%
  • 18.
  • 19.
  • 20. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19)
  • 21. Fig 6: Simplified Representation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Lifecycle and Potential Drug Targets (Sanders
  • 22. Table 1: Summary of Pharmacology for Select Proposed COVID-19 Treatments (Sanders et al., 2020)
  • 23. Table 1 Cont. : Summary of Pharmacology for Select Proposed COVID-19 Treatments (Sanders et al., 2020)
  • 24. • BCG vaccination prevents severe forms of tuberculosis in children and diversion of local supplies may result in neonates not being vaccinated, resulting in an increase of disease and deaths from tuberculosis. • In the absence of evidence, WHO does not recommend BCG vaccination for the prevention of COVID-19. • WHO continues to recommend neonatal BCG vaccination in countries or settings with a high incidence of tuberculosis. BCG Vaccine, According to WHO
  • 25.
  • 26. • Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020 Apr 13. • Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J Adv Res. 2020 16;24:91-98. • Bacille Calmette-Guérin ( BCG ) vaccination and COVID-19. (2020). 36(April), 2019–2020. www.who.int/news- room/commentaries. • Kumar, M. (2020). The FDA-approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells. References