Have a personal or library account? Click to login
Novel Sars-Cov-2 Pandemic Transmission With Ongoing Antiviral Therapies And Vaccine Design Cover

Figures & Tables

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])

NspsFunctions
Nsp1Degrade Cellular mRNA and constrain signaling of IFN
Nsp3Blocking of host innate immune response and cut polypeptides
Nsp4Development of double membrane vesicles
Nsp5Constrain IFN signaling and cleave polypeptides
Nsp6Restrict expansion of auto phagosomes
Nsp7Nsp8 and Nsp12 co-factor
Nsp8Nsp7 and Nsp12 co-factor
Nsp9Interact with RNA binding and dimerization
Nsp10Nsp14 and Nsp16 support protein
Nsp12Primer, which function depends upon Rd-Rp
Nsp135 prime triphosphatase and RNA helicase
Nsp14Exo ribonuclease activity
Nsp15Exo ribonuclease activity
Nsp16Regulate immune responses negatively and 2’-O-MTase

In process-Vaccines with its Candidates & Phase Trials

ManufacturerVaccine candidatePhase trials [31]References
Moderna DNA-based vaccines which code or a stabilized form of of SARS-CoV-2 spike proteinPhase 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 proteinsBegins the human trials https://www.curevac.com/en/covid-19/
Inovio DNA-based vaccinesHuman trials to start in later June https://www.inovio.com/our-focus-serving-patients/covid-19/
Takis Biotech DNA-based vaccinesResults of dose-response trials to be published in June[27]
Zydus Cadila DNA-based vaccinesProject is in pre-clinical trials https://zyduscadila.com/
Stemirna Therapeutics mRNA-based vaccinesClinical trials expected to start in Mid-April http://www.stemirna.com/en/index.aspx
Imperial College London DNA-based vaccinesHuman trial started https://www.imperial.ac.uk/covid-19-vaccine-trial/
Novavax Recombinant-protein nanoparticles derived fromPhase I/II started in May 2020 https://www.novavax.com/covid-19-coronavirus-vaccine-candidate-updates
Vaxart Oral vaccine half of 2020Phase I begins in the second https://vaxart.com/
GlaxoSmithKline (GSK) A protein-based vaccine with the use of adjuvantAnimal 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 candidateAnimal trials https://www.vido.org/covid19/covid-19-news/
Sanofi Recombinant DNA platform swapping the part of corona-virus with genetic materialPhase 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-2Pre-clinical stage https://www.geovax.com/news/geovax-progresses-in-coronavirus-covid-19-vaccine-development-program
Cansino Biologics Viral vector-based vaccinePhase 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 proteinPre-clinical stage https://www.grefex.com
Generex Biotechnology Te firm uses insect cells from fruit fies to produce viral antigensEx-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 strategyAdvantagesDisadvantagesReferences
mRNA vaccinesEasy preparation,High Adaptability,Can induce strong immune responsesHigh unstable under physiological conditions[24]
DNA vaccinesEasy preparationNeutralizing antibodies with high titerLow immune responsesMay induce toxicity with repeated doses[24]
Viral vector vaccinesInduces high humoral and cellular immune responsesPre-existing immunity will be a problem[11]
Subunit vaccinesNeutralizing antibodies with high titer,Induces high humoral and cellular immune responsesHigh costLow immunity,Repeated doses may require[11]
Attenuated virus vaccinesQuick development,High immune responsesGenotypic & phenotypic reversion possible[25]
Inactivated virus vaccinesEasy preparation,Neutralizing antibodies with high titerNot applicable for immunosuppressed individuals[25]

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

ProteinSARS-CoVSARS-CoV-2
8aPresentAbsent
8b84 amino acids121 amino acids
3b154 amino acids22 amino acids
DOI: https://doi.org/10.21307/PM-2021.60.1.02 | Journal eISSN: 2545-3149 | Journal ISSN: 0079-4252
Language: English, Polish
Page range: 13 - 20
Submitted on: Jul 1, 2020
Accepted on: Oct 1, 2020
Published on: Mar 24, 2021
Published by: Polish Society of Microbiologists
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year

© 2021 Muhammad Yameen, Sara Sattar, Ayesha Khalid, Muhammad Aamir Aslam, Nishat Zafar, Muhammad Hassan Saeed, Muhammad Haseeb Arif, Muhammad Jahangeer, Azka Qadeer, Shoukat Hussain, Muhammad Aamir, Sania Mukhtar, Huma Nasir, Asif Shahzad, published by Polish Society of Microbiologists
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.