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THE GENOTYPE AND LİFECYCLE OF
COVID-19
BAKİ YAMAN
CONTENT
 What İs Corona Virus ?
 Comparison of COVID-19 With
Others
 Genome structure of COVID-19
 Potential treatments of COVID-19
Summary
 Life Cycle of COVID-19
 References
What İs Corona Virus
?
Coronaviruses are involved in human and vertebrate’s diseases
that cause severe acute respiratory syndrome
The recent emergence of novel coronavirus with an outbreak of
unusual viral pneumonia in Wuhan, China
Based phylogenetic relationships of COVID19, it belongs to
genera Betacoronavirus
Genome Structure of COVID-
19
 The genome is single-stranded positive-sense
RNA (+ssRNA) molecule.
 Contains at least six ORFs.
 The First ORFs (ORFa/b) located at 5’ end,
about two-thirds of the whole genome.
Encodes 16 NSP (non-structural proteins).
 Other ORFs located at 3’ end and encode
structural proteins
Life Cycle of COVID19
1) Spike protein binds to host cell reseptor, enter the
cell and envelope is peeled off for RNA release
2) pp1a and pp1ab proteins are produced, cleaved
by protease to make total 16 NSPs
3) Subgenomic RNAs produced by transcription and
translation into structural proteins
4) Nucleoprotein complex occured and enter to ER
with structural proteins
5) They merge into the complete virus particle in
golgi
6) Excreted to extracellular region through golgi
vesicles
SARS-CoV 2 (COVID19) Vs SARS-CoV and
MERS-CoV They are all belongs to Betacoronaviruses
 At 5’ end, Pb1ab is the first ORF of whole genome lenght encoding NSPs, but different
bp among ß-coronaviruses
 Even at spike proteins and arrangement of N, E, M proteins there are differences.and
 Less similar to SARS-CoV (about 79%) and MERS-CoV (about 50%).
Potential Treatment of COVID 19
There are different methods for treatment of COVID19
 Antiviral drugs using for interfere of viral replication machinery in target
cells
 Oseltamivir, peramivir, and zanamivir are neuraminidase inhibitors which
help to COVID19 treatment
 SARS-CoV-Specific Human Monoclonal Antibody (CR3022)
 CRISPR/Cas13d System is another treatment way
Summary
 COVID19 belongs to ß-coronaviruses and causes severe acute respiratory
sendrome.
 This virus has a large +ssRNA genome, encode NSPs and structural proteins
 There are several stages for production of complete virus particle
 Less similar to SARS-CoV (about 79%) and MERS-CoV (about 50%).
 Even there are different possible methods which help to treatment of COVID19, no
certain way for cure
References
 Mousavizadeh, L., Ghasemi, S., (2020), Genotype and phenotype of COVID-19: Their roles in
pathogenesis, Journal of Microbiology , 1684-1182, https://doi.org/10.1016/j.jmii.2020.03.022
 Alanagreh, L., Alzoughool, F., Atoum, M., (2020), The Human Coronavirus Disease COVID-19:
Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms, MDPI, 9 (331),
https://dx.doi.org/10.3390/pathogens9050331
 Fan, H.-H.; Wang, L.-Q.; Liu, W.-L.; An, X.-P.; Liu, Z.-D.; He, X.-Q.; Song, L.-H.; Tong, Y.-G.
Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-
novel coronavirus (2019-nCoV) related coronavirus model. Chin. Med. J. 2020.
 Colson, P.; Rolain, J.-M.; Lagier, J.-C.; Brouqui, P.; Raoult, D. Chloroquine and
hydroxychloroquine as available weapons to fight COVID-19. Int. J. Antimicrob. Agents 2020,
55, 105932.
 Yao, X.; Ye, F.; Zhang, M.; Cui, C.; Huang, B.; Niu, P.; Liu, X.; Zhao, L.; Dong, E.; Song, C.; et
al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for
the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin. Infect.
Dis. 2020.
Thanks for your attention
bakiyaman5@gmail.com

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What is Covid 19 ?

  • 1. THE GENOTYPE AND LİFECYCLE OF COVID-19 BAKİ YAMAN
  • 2. CONTENT  What İs Corona Virus ?  Comparison of COVID-19 With Others  Genome structure of COVID-19  Potential treatments of COVID-19 Summary  Life Cycle of COVID-19  References
  • 3. What İs Corona Virus ? Coronaviruses are involved in human and vertebrate’s diseases that cause severe acute respiratory syndrome The recent emergence of novel coronavirus with an outbreak of unusual viral pneumonia in Wuhan, China Based phylogenetic relationships of COVID19, it belongs to genera Betacoronavirus
  • 4. Genome Structure of COVID- 19  The genome is single-stranded positive-sense RNA (+ssRNA) molecule.  Contains at least six ORFs.  The First ORFs (ORFa/b) located at 5’ end, about two-thirds of the whole genome. Encodes 16 NSP (non-structural proteins).  Other ORFs located at 3’ end and encode structural proteins
  • 5. Life Cycle of COVID19 1) Spike protein binds to host cell reseptor, enter the cell and envelope is peeled off for RNA release 2) pp1a and pp1ab proteins are produced, cleaved by protease to make total 16 NSPs 3) Subgenomic RNAs produced by transcription and translation into structural proteins 4) Nucleoprotein complex occured and enter to ER with structural proteins 5) They merge into the complete virus particle in golgi 6) Excreted to extracellular region through golgi vesicles
  • 6. SARS-CoV 2 (COVID19) Vs SARS-CoV and MERS-CoV They are all belongs to Betacoronaviruses  At 5’ end, Pb1ab is the first ORF of whole genome lenght encoding NSPs, but different bp among ß-coronaviruses  Even at spike proteins and arrangement of N, E, M proteins there are differences.and  Less similar to SARS-CoV (about 79%) and MERS-CoV (about 50%).
  • 7. Potential Treatment of COVID 19 There are different methods for treatment of COVID19  Antiviral drugs using for interfere of viral replication machinery in target cells  Oseltamivir, peramivir, and zanamivir are neuraminidase inhibitors which help to COVID19 treatment  SARS-CoV-Specific Human Monoclonal Antibody (CR3022)  CRISPR/Cas13d System is another treatment way
  • 8. Summary  COVID19 belongs to ß-coronaviruses and causes severe acute respiratory sendrome.  This virus has a large +ssRNA genome, encode NSPs and structural proteins  There are several stages for production of complete virus particle  Less similar to SARS-CoV (about 79%) and MERS-CoV (about 50%).  Even there are different possible methods which help to treatment of COVID19, no certain way for cure
  • 9. References  Mousavizadeh, L., Ghasemi, S., (2020), Genotype and phenotype of COVID-19: Their roles in pathogenesis, Journal of Microbiology , 1684-1182, https://doi.org/10.1016/j.jmii.2020.03.022  Alanagreh, L., Alzoughool, F., Atoum, M., (2020), The Human Coronavirus Disease COVID-19: Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms, MDPI, 9 (331), https://dx.doi.org/10.3390/pathogens9050331  Fan, H.-H.; Wang, L.-Q.; Liu, W.-L.; An, X.-P.; Liu, Z.-D.; He, X.-Q.; Song, L.-H.; Tong, Y.-G. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019- novel coronavirus (2019-nCoV) related coronavirus model. Chin. Med. J. 2020.  Colson, P.; Rolain, J.-M.; Lagier, J.-C.; Brouqui, P.; Raoult, D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int. J. Antimicrob. Agents 2020, 55, 105932.  Yao, X.; Ye, F.; Zhang, M.; Cui, C.; Huang, B.; Niu, P.; Liu, X.; Zhao, L.; Dong, E.; Song, C.; et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin. Infect. Dis. 2020.
  • 10. Thanks for your attention bakiyaman5@gmail.com

Editor's Notes

  1. Coronaviruses are involved in human and vertebrate’s diseases and members of subfamily Coronavirinae in the family Coronaviridae and order Nidovirales. The recent emergence of a novel coronavirus with an outbreak of unusual viral pneumonia in Wuhan, China and then pandemic outbreak is 2019-nCoV or COVID-19. Based on phylogenetic relationships of COVİD-19, it belongs to genera Betacoronavirus which has close similarity of sequence of COVID19 to that of severe acute respiratory syndrome-related coronaviruses (SARSr-CoV) COVID19 uses ACE2 as entry reseptor like SARS-CoV. These similarities of the SARSCoV- 2 to the one that caused the SARS outbreak (SARSCoVs) the Coronavirus Study Group of the International Committee on Taxonomy of Viruses termed the virus as SARS-CoV-2. Coronavirus cases are about 6 Mn, deaths are 369,127 and about 2 Mn recovered
  2. The CoVs genome is a single-stranded positive-sense RNA (+ssRNA) molecule. The genome size ranges between 27–32 kbp, one of the largest known RNA viruses. The genomic structure of CoVs contains at least six open reading frames (ORFs). The first ORFs (ORF1a/b), located at the 5’ end, about two-thirds of the whole genome length, and encodes 16 non-structural proteins (NSP1- NSP16). These NSPs are processed to form a replication–transcription complex (RTC) that is involved in genome transcription and replication. For example, NSP3 and NSP5 encode for Papain-like protease (PLP) and 3CL-protease, respectively. Both proteins function in polypeptides cleaving and block the host innate immune response. NSP12 encodes for RNA-dependent RNA polymerase (RdRp). NSP15 encodes for RNA helicase. Other ORFs are located on 3’ end encodes at least four structural proteins: envelop glycoprotein spike (S), responsible for recognizing host cell receptors. Membrane (M) proteins, responsible for shaping the virions. The envelope (E) proteins, responsible for virions assembly and release. The nucleocapsid (N) proteins are involved in packaging the RNA genome and in the virions and play roles in pathogenicity as an interferon (IFN) inhibitor. In addition to the four main structural proteins, there are structural and accessory proteins that are species-specific, such as HE protein, 3a/b protein, and 4a/b protein.
  3. When the spike protein of SARS-CoV-2 binds to the receptor of the host cell, the virus enters the cell, and then the envelope is peeled off, which let genomic RNA be present in the cytoplasm. The ORF1a and ORF1b RNAs are made by genomic RNA, and then translated into pp1a and pp1ab proteins, respectively. Protein pp1a and ppa1b are cleaved by protease to make a total of 16 nonstructural proteins. Some nonstructural proteins form a replication/transcription complex (RNA-dependent RNA polymerase, RdRp), which use the (+) strand genomic RNA as a template. The (+) strand genomic RNA produced through the replication process becomes the genome of the new virus particle. Subgenomic RNAs produced through the transcription are translated into structural proteins (S: spike protein, E: envelope protein, M: membrane protein, and N: nucleocapsid protein) which form a viral particle. Spike, envelope and membrane proteins enter the endoplasmic reticulum, and the nucleocapsid protein is combined with the (+) strand genomic RNA to become a nucleoprotein complex. They merge into the complete virus particle in the endoplasmic reticulum-Golgi apparatus compartment, and are excreted to extracellular region through the Golgi apparatus and the vesicle.
  4. İn all Betacoronaviruses The 5’ UTR and 3’ UTR are involved in inter- and intramolecular interactions and are functionally important for RNA-RNA interactions and for binding of viral and cellular proteins. At 5’ end, Pb1ab is the first ORF of the whole genome length encoding non-structural proteins of 29844bp (7096aa), 29751bp (7073aa) and 30119bp (7078) in COVID-19, SARS-CoV; and MERS-CoV, respectively. Even with comparison of the spike protein at 3’ end, among the coronaviruses specifically these three betacoronaviruses, the difference was visualized, 1273aa, 21493aa, and 1270aa. Genetically, COVID-19 was less similar to SARS-CoV (about 79%) and MERS-CoV (about 50%). The arrangement of nucleocapsid protein (N), envelope protein(E), and membrane protein (M) among betacoronaviruses are different
  5. Antiviral drugs usually interfere with the viral replication machinery in the target cells. Given that viruses have similar actions of infection, different studies suggest the use of successful antiviral drugs for the treatment of COVID-19. Oseltamivir, peramivir, and zanamivir are neuraminidase inhibitors that have been used for influenza treatment. A recent report suggests the potential activity of these drugs against SAS-CoV-2 by interfering with the virions budding and releasing from the cell. However, this virus uses different mechanisms other than neuraminidase facilitate its release out of the infected cell. Another recent study suggests that ribavirin if combined with interferon-ß might be a promising drug for inhibition of SARS-CoV-2 replication. Although this claim was based on previous in vitro findings, other studies have shown the same results. There are many drugs with general antiviral activity; that can interfere with vial entry or blocking the virus. CR3022 is a human monoclonal antibody previously isolated from a convalescent patient, used to target a highly conserved epitope that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. CR3022 might have the potential to be candidate therapeutics for the and treatment of COVID-19 patients, especially in life-threatening situations. Currently, there is an ambitious study suggesting that CRISPR/Cas13d system can be used to accurately digest the SARS-CoV-2 RNA genome, hence limiting its ability to reproduce. Theoretically, this approach is excellent not only against COVID-19 but for the treatment and prevention of different RNA viruses’ infections. However, we have no idea if it is practical or not.