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Novel Sars-Cov-2 Pandemic Transmission With Ongoing Antiviral Therapies And Vaccine Design

Muhammad Yameen
Muhammad Yameen
, 
Sara Sattar
Sara Sattar
, 
Ayesha Khalid
Ayesha Khalid
, 
Muhammad Aamir Aslam
Muhammad Aamir Aslam
, 
Nishat Zafar
Nishat Zafar
, 
Muhammad Hassan Saeed
Muhammad Hassan Saeed
, 
Muhammad Haseeb Arif
Muhammad Haseeb Arif
, 
Muhammad Jahangeer
Muhammad Jahangeer
, 
Azka Qadeer
Azka Qadeer
, 
Shoukat Hussain
Shoukat Hussain
, 
Muhammad Aamir
Muhammad Aamir
, 
Sania Mukhtar
Sania Mukhtar
, 
Huma Nasir
Huma Nasir
 and 
Asif Shahzad
Asif Shahzad
   | Mar 24, 2021
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Article Category: research-article
Published Online: Mar 24, 2021
Page range: 13 - 20
Received: Jul 01, 2020
Accepted: Oct 01, 2020
DOI: https://doi.org/10.21307/PM-2021.60.1.02
Keywords
© 2021 Wenbing Yameen et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1.

The structure of SARS-CoV-2. ssRNA genome (26–32 kb) in the center, four structural proteins: spike glycoprotein (S), envelope protein (E), matrix protein (M), and nucleocapsid protein (N). Apart from these, many accessory proteins are also present but not shown in the Figure [22].
The structure of SARS-CoV-2. ssRNA genome (26–32 kb) in the center, four structural proteins: spike glycoprotein (S), envelope protein (E), matrix protein (M), and nucleocapsid protein (N). Apart from these, many accessory proteins are also present but not shown in the Figure [22].

Fig. 2.

General mode of replication of SARS-CoV. Starting with the attachment of viral S protein, present on the envelope, with ACE-2 receptor on lung cells the viral RNA is released inside the cytoplasm through membrane fusion. Once inside the cell +ssRNA act as mRNA and the host ribosome will start making viral proteins (2 polyproteins and structural protein) which help viral genomic replication and capsid formation, after which packaging of viral RNA inside a capsid occurs. Once the virion particles are mature they are released through lysis or exocytosis.
General mode of replication of SARS-CoV. Starting with the attachment of viral S protein, present on the envelope, with ACE-2 receptor on lung cells the viral RNA is released inside the cytoplasm through membrane fusion. Once inside the cell +ssRNA act as mRNA and the host ribosome will start making viral proteins (2 polyproteins and structural protein) which help viral genomic replication and capsid formation, after which packaging of viral RNA inside a capsid occurs. Once the virion particles are mature they are released through lysis or exocytosis.

Fig. 3.

ORF’s of the genome of HB01 strain of SARS-CoV-2 (previously called 2019-nCoV) are shown. Structural proteins are encoded at the 3’ terminus and non-structural at the 5’ terminus (Modified from [40]).
ORF’s of the genome of HB01 strain of SARS-CoV-2 (previously called 2019-nCoV) are shown. Structural proteins are encoded at the 3’ terminus and non-structural at the 5’ terminus (Modified from [40]).

Te functions of non-structural proteins in the replication of coronaviruses are shown (Modified from [8])

Nsps Functions
Nsp1 Degrade Cellular mRNA and constrain signaling of IFN
Nsp3 Blocking of host innate immune response and cut polypeptides
Nsp4 Development of double membrane vesicles
Nsp5 Constrain IFN signaling and cleave polypeptides
Nsp6 Restrict expansion of auto phagosomes
Nsp7 Nsp8 and Nsp12 co-factor
Nsp8 Nsp7 and Nsp12 co-factor
Nsp9 Interact with RNA binding and dimerization
Nsp10 Nsp14 and Nsp16 support protein
Nsp12 Primer, which function depends upon Rd-Rp
Nsp13 5 prime triphosphatase and RNA helicase
Nsp14 Exo ribonuclease activity
Nsp15 Exo ribonuclease activity
Nsp16 Regulate immune responses negatively and 2’-O-MTase

In process-Vaccines with its Candidates & Phase Trials

Manufacturer Vaccine candidate Phase trials [31] References
Moderna DNA-based vaccines which code or a stabilized form of of SARS-CoV-2 spike protein Phase 3 starts in the 1st week of July. It will include the study of 30,000 patients [4]
Curevac Lab-made RNA to spur the production of corona proteins Begins the human trials https://www.curevac.com/en/covid-19/
Inovio DNA-based vaccines Human trials to start in later June https://www.inovio.com/our-focus-serving-patients/covid-19/
Takis Biotech DNA-based vaccines Results of dose-response trials to be published in June [27]
Zydus Cadila DNA-based vaccines Project is in pre-clinical trials https://zyduscadila.com/
Stemirna Therapeutics mRNA-based vaccines Clinical trials expected to start in Mid-April http://www.stemirna.com/en/index.aspx
Imperial College London DNA-based vaccines Human trial started https://www.imperial.ac.uk/covid-19-vaccine-trial/
Novavax Recombinant-protein nanoparticles derived from Phase I/II started in May 2020 https://www.novavax.com/covid-19-coronavirus-vaccine-candidate-updates
Vaxart Oral vaccine half of 2020 Phase I begins in the second https://vaxart.com/
GlaxoSmithKline (GSK) A protein-based vaccine with the use of adjuvant Animal trials https://www.gsk.com/en-gb/media/press-releases/ gsk-and-curevac-to-develop-next-generation- mrna-covid-19-vaccines/
University of Saskatchewan A protein-based candidate Animal trials https://www.vido.org/covid19/covid-19-news/
Sanofi Recombinant DNA platform swapping the part of corona-virus with genetic material Phase 1 to be started in the last quarter of 2020 https://www.sanofi.com/en/about-us/our-stories/sanofi-s-response-in-the-fight-against-covid-19
Geovax Labs/ Bravovax Develop a live horsepox virus which will be modified to express protein fragments from SARS-CoV-2 Pre-clinical stage https://www.geovax.com/news/geovax-progresses-in-coronavirus-covid-19-vaccine-development-program
Cansino Biologics Viral vector-based vaccine Phase II – All volunteers developed neutralizing antibodies [42]
Grefex DNA-based vaccines: Adenovirus based vector vaccines that involve a harmless virus that will express foreign genes like SARS-CoV-2 spike protein Pre-clinical stage https://www.grefex.com
Generex Biotechnology Te firm uses insect cells from fruit fies to produce viral antigens Ex-Vivo Human Immune System screening of 33 Ii-Key-SARS-CoV-2 peptides https://www.generex.com/covid-19

Diferent Vaccine Strategies with their Advantages and Disadvantages

Vaccine strategy Advantages Disadvantages References
mRNA vaccines Easy preparation,High Adaptability,Can induce strong immune responses High unstable under physiological conditions [24]
DNA vaccines Easy preparationNeutralizing antibodies with high titer Low immune responsesMay induce toxicity with repeated doses [24]
Viral vector vaccines Induces high humoral and cellular immune responses Pre-existing immunity will be a problem [11]
Subunit vaccines Neutralizing antibodies with high titer,Induces high humoral and cellular immune responses High costLow immunity,Repeated doses may require [11]
Attenuated virus vaccines Quick development,High immune responses Genotypic & phenotypic reversion possible [25]
Inactivated virus vaccines Easy preparation,Neutralizing antibodies with high titer Not applicable for immunosuppressed individuals [25]

Te diferences found in proteins of SARS-CoV and SARS-CoV-2

Protein SARS-CoV SARS-CoV-2
8a Present Absent
8b 84 amino acids 121 amino acids
3b 154 amino acids 22 amino acids
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