Author: James Buckley

Abstract

The ongoing COVID-19 pandemic has brought epidemiology and virology into the public eye through news and media platforms in an unprecedented way. This short review paper explains the virology of coronaviruses and summarises current studies of COVID-19 to help inform the public in these areas.

What is a Virus?

A virus is a particle which causes disease. It is non-living and is usually made up of genetic material and proteins. Viruses infect specific cells within a host organism and use the cell’s organelles to produce more virus particles. Then, these new virus particles leave the original cell and infect more cells within the host organism as the infection progresses.

What is a Coronavirus?

In the past 20 years coronaviruses have been recognised as an upcoming threat to humans [1,2,3,4]. These viruses have four genera: alphacoronavirus, betacoronavirus, deltacoronavirus and gammacoronavirus  [5]. The alpha and beta types are mainly found in mammals (mostly in bats) whereas the gamma and delta types are mainly found in birds [6]. Coronaviruses are positive strand RNA viruses (+RNA) with a protein envelope encasing the genetic material [5]. These viruses have very large genomes which are between 26,000 and 32,000 nucleotides long [7]. Each virus has spike surface glycoproteins (S) which bind to specific receptors on host cells and determine host tropism [8,9].

The mechanisms of coronavirus replication and pathogenesis are highly complex and not yet fully understood [1]. This is because coronaviruses have an exceptionally large genome and consequently produce many proteins that have roles within the host-virus interplay as well as proteins used for basic viral replication [1]. The host- virus interplay includes: counteracting the host’s antiviral defences and interfering with the host cell to create an optimal environment for viral replication [1]. This complex proteome creates a highly complex replication cycle which needs to be studied further to help develop antiviral medications and treatments for human-infecting coronaviruses (HCoVs) [1].
Only alpha and beta type coronaviruses can infect humans due to their specific host cell tropisms [10]. There are 4 main HCoVs (229E, NL63, OC43, and HKU1) which are endemic in the human population and account for 10-30% of respiratory tract infections worldwide in adults [10]. Recent epidemics relating to HCoVs include SARS in Hong Kong and China (2002), MERS in Saudi Arabia (2012), and now the present situation with COVID-19.

Current Research Findings on COVID-19

The WHO detected COVID-19 in samples from the Huanan Seafood Market, China which is thought to be the source of the virus [11]. COVID-19 or CoV-SARS-2 is a betacoronavirus of the subgenus bolutinum [11]. It is a zoonotic virus made up of part bat coronavirus and part coronavirus from another, currently unknown animal [12]. Further studies found that snakes are a likely repository for the virus [12] and that COVID-19 has 88-89% similarity to 2 bat coronaviruses [4].

COVID-19 is approximately 30,000 nucleotides long and has 79.5% sequence homology with the 2002 SARS coronavirus (CoV-SARS) [13,14,15]. Also, the S protein on COVID-19 has 75% similarity with the S protein of SARS, indicating both of these viruses attach to a similar receptor binding site (RBD) on the host [16].

Figure 1: A scanning electron microscope image of SARS-CoV-2. Yellow has been used to colour the coronavirus particles and purple shows the host cells.


COVID-19 attaches to the ACE2 receptor (angiotensin-converting enzyme 2) in the lungs to infect humans [11]. ACE2 is mainly expressed on type 1 and 2 alveolar epithelial cells as well as being found in the epithelium of the oral cavity and on enterocytes in the small intestine [17]. It has been shown that men have higher levels of ACE2 in the lungs than women [11].

When COVID-19 binds to ACE2 it upregulates expression of the ACE2 protein so the virus can enter cells more easily, this leads to damage being caused to alveolar cells [11]. The receptor binding ability of COVID-19 is 10 to 20x stronger than that of SARS [11] which could indicate COVID-19 is more infectious than SARS was. A study by Woelfel et Al. (2019) found evidence of COVID-19 causing an independent infection in the throat and lungs of patients. It found viral sgRNAs (sub-genomic RNAs) in both throat and alveolar cells and a G6446A exchange was detected in a throat swab of one patient, showing a difference in viral genomes in the throat and lungs of the patient [19].

Viral sgRNAs are only produced in infected cells and are not found in virions which means they are strong evidence for cells being infected by the virus [19]. The independent infection in the throat would increase viral shedding causing the virus to have a more efficient transmission than SARS, which could not infect throat cells [19]


Conclusion

Further research needs to be conducted on COVID-19 to determine its specific mechanisms of reproduction and infection to be able to produce a vaccine or antiviral drugs to protect humanity from further outbreaks. A vaccine could help stop the virus becoming endemic in the human population or protect the most vulnerable if this occurs. HCoVs should continue to be an active research area as new zoonotic viruses could be produced at any time and humanity needs to find new ways of treating these diseases.


Glossary:

Glossary

  1. Glossary
  2. Zoonotic – A disease transmitted from animals to humans
  3. Virions – Virus particles outside of a host cell
  4. Viral shedding – The release of virus progeny from a host cell that has been infected after successful viral replication
  5. Endemic – A disease that circulates in the population continually (e.g. seasonal flu)
  6. Host tropism - The infection specificity of certain pathogens to particular host cells and tissues
  7. S protein/ spike surface glycoprotein - The spike surface protein on a coronavirus. This protein is used to attach the virus to complementary receptors on host cells before the cell is infected
  8. Alveolar epithelial cells - Cells which line the alveoli in the lungs and come into contact with air that has been breathed in
  9. Epithelium - A thin layer of tissue lining body structures on the outer layer of the body (e.g. in the stomach or the topmost layer of the skin)
  10. Enterocytes - Cells that line the small intestine
  11. Genera – A principal taxonomic category which ranks above species and below family
  12. Sub-genomic RNAs - Molecules only found in cells that have been infected and which are not found in virions or before a coronavirus infects cells
  13. Pathogenesis – How a disease develops
  14. Host-virus interplay – How the virus particles interact with the host during an infection.

Biography:

James Buckley is a 19 year old student, currently studying Biosciences at Durham University. He has particular interests in immunology, plant sciences and physiology and wants to persue a research career in the future. In his spare time he sings in operas, plays badminton and tutors sciences and mathematics. He is currently an editor for life sciences at the Young Scientist’s Journal.


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