Understanding the new Coronavirus SARS-CoV-2

Cornavirus SARS-CoV-2 Covid-19

A false color image of SARS-CoV-2 virions emerging from an infected cell. The image was taken with a scanning electron microscope. Credit: NIAID-RML

There is always hope. 

Understanding SARS-CoV-2

Virus Name:  Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2).

Size: 60–140 nm (100 million of these virus particles can fit on the head of a pin).

Disease Name: COVID-19 (Coronavirus Disease 2019)

SARS-CoV-2 3D model

SARS-CoV-2 3D model showing the spike proteins on the surface of the virus. Credit: NIH

Origin of SARS-CoV-2: Coronaviruses come from a family of viruses called Coronaviridae and are capable of causing disease in mammals and birds. They are known to have transmitted across species and can infect humans such as the coronaviruses SARS (SARS-CoV) in 2002 and MERS (MERS-CoV) in 2012. In total 7 Coronaviruses are known to sicken humans but the 2 previously named and the novel SARS-CoV-2 are the most severe.1 The name Corona comes from latin, meaning “Crown” due to the crownlike appearance of the virus under an electron microscope.

Genetic similarity of SARS-CoV-2 to a known bat coronavirus

The genetic analysis showing the similarity of SARS-CoV-2 to a known bat coronavirus. The S protein is highlighted.

The animal origin of SARS-CoV-2 is currently unknown but both SARS (2002) and MERS (2012) are believed to have originated in bats and then been transmitted to humans via market civets and dromedary camels respectively.2 Genetic analysis of SARS-CoV-2 showed it was 96% identical to a known bat coronavirus 3 and 92% identical to a known Pangolin coronavirus found in Malaysia.4 It is suspected that a similar animal had the SARS-CoV-2 strain and transferred it to a human. The cluster of initial cases around the Huanan Seafood Wholesale Market in Wuhan5 (that also sold wild animals for food) casts suspicion that perhaps the cross species transmission first occurred there. However, ultimately we may never know. 

Method of cellular entry: SARS-CoV-2 has a protein on its surface called S protein (the S stands for spike) which attaches to a protein on the surface of human cells called ACE2 (Angiotensin-converting enzyme 2).

SARS CoV-2 S spike protein

A 3D printed model of the spike (S) protein of SARS-CoV-2. Credit: NIH

This enzyme plays an important part in lowering blood pressure but in this case it cleaves (cuts) the attached viral protein which activates the viral fusion machinery. The virus fuses with the cell and inserts its code inside. Human cells in the nose, throat and lungs have ACE2 on their surfaces (other cells also have them). 

Method of replication: The cell is unable to distinguish between viral code and its own and so it produces and assembles new virus particles. These bud out of the infected cells (sometimes killing the cells in the process) and subsequently go on to infect more cells. This exponential cycle continues until the immune system detects the virus particles and springs into action.

Why is SARS-CoV-2 so infectious?

If SARS and MERS have crossed into humans before in 2002 and 2012 respectively why is SARS-CoV-2 infecting and killing more people? In short, the SARS-CoV-2 is slightly different genetically. This changes it in a way that makes it much more efficient at entering and replicating in humans. The current SARS-CoV-2 is about 86% identical to the SARS-CoV that passed into the human population in 2002 (the first pandemic of the 21st century). The reason why it’s more infectious borders on the cutting edge of the research. There are two candidates and both may be correct. 

Firstly there is data from a paper just out that suggests the SARS-CoV-2 S protein sticks 10-20 times stronger to the ACE2 enzyme on our human cells compared with the 2002 virus, SARS-CoV.6 This paper is currently awaiting peer review. This would mean it is much easier for the virus to successfully attach which translates to a faster spread and stronger infection. However, another paper found similar affinity for the human ACE2 compared with the 2002 virus, SARS-CoV7 (despite this not being the main focus of the paper).  The jury is out on this one until there are more studies.

Secondly, scientists have identified a mutation that has caused a furin activation site in the S protein, meaning it can be cut far easier to activate the cell fusion machinery.8 This would also speed up the ease and rate of infection. It is possible that both the increased affinity to ACE2 and the furin activation site are contributing to the difference to what we saw in 2003 and 2012.

What do we know about the spread?

Hubei Province China

Hubei Province China where SARS-CoV-2 jumped across species. Credit: Google Maps

First case: Patient zero is unknown. Earliest suspected case – 17th November 2019, Hubei province but evidence for this is still inconclusive. Earliest confirmed case – 8th December in Wuhan. The Chinese government’s search for patient zero continues. Genetic analysis of the viral mutation rate suggests initial infection most likely between late November or early December.9

Recognition of the new virus: In mid December 2019 a number of similar cases of unknown cause were being seen by Chinese authorities.  The World Health Organization (WHO) was notified on the 31st December of a cluster of 41 cases of pneumonia of unknown cause.

Isolation of virus: China isolated the virus from a patient on the 7th January.

Viral genetic code published:  China published the complete genetic code of the virus on the 10th January. This allowed the rapid development of testing kits to begin anywhere in the world and scientific analysis to begin with the aim of finding a therapy, cure or vaccine.

First recorded case outside of China: On the 13th January Thailand reported its first case of COVID-19.

Since then the infection has tragically spread across the world with thousands dying daily.

How long until we find a cure for COVID-19?

How long will until we find a cure? There are 3 avenues that scientists and pharmaceutical companies across the world are working tirelessly on. 

  1. Find a drug. This is our best hope in the short-term. The fastest way is to try existing drugs and cocktails of drugs to see if anything works against the infection while working to develop new drugs that might work. Remdesivir is a leading candidate which was originally manufactured for Ebola during the Ebola epidemic of 2013-16. It is manufactured by Gilead Sciences and is going into 2 more trials.10

    Favipiravir, a potential candidate to help treat COVID-19. Credit: HISUN

     

    Another candidate is Avigan (or Favipiravir) from FujiFilm11 that is in phase 3 trials.12 China has accepted this drug to treat COVID-19 and Japan is currently testing it. The final short-term candidates are anti-inflamatory drugs to stop what is known as the ‘Cytokine storm’ which is why people end up on ventilators. If any candidates stop the inflamation flooding the lungs then that will save lives.

  2. Use antibody therapy. The plasma of people who have recovered from COVID-19 will contain antibodies that neutralize SARS-CoV-2. This can be given to treat patients. These antibodies can also be manufactured in a lab and there are a number of companies such as Regeneron in Ireland that have antibodies waiting to go into clinical trials by early summer.13 
  3. Vaccine development. This is our best hope at preventing people from becoming infected with SARS-CoV-2 but it will take a long time before we have vaccines. Typically vaccines are developed over 5-7 years but the the first candidate is hoping to be made in 18 months. Moderna has already begun phase 1 testing with its mRNA vaccine.14 There is no guarantee that this vaccine will be effective and so much testing has to happen to ensure it is safe before it could ever be released. Many companies in collaboration with universities and laboratories are working on different vaccine candidates.

What can I do to stop the spread of the disease?

  1. Follow and keep up-to-date with the guidelines of the CDC and your public health authorities.
  2. Social distancing and education is key – the virus cannot spread without your help.
  3. Protect the vulnerable – the mortality rate for the elderly is much higher than for younger people so do what you can for the elderly in your community or family so they don’t have to go outside and potentially expose themselves to the virus. 
  4.  Wash your hands and remember you could have the disease with no symptoms, so take precautions with the elderly in your family.

Don’t lose hope and do your part in the fight against SARS-CoV-2. We will overcome it despite the difficult months that lie ahead.

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References

  1. CDC. Human Coronavirus types
  2. Cui J et al., Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019 Mar;17(3):181-192
  3. Peng Zhou et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798): 270–273.
  4. Tommy Tsan-Yuk Lam et al., Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. 2020, Nature.
  5. David S. Hui et al., The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health — The latest 2019 novel coronavirus outbreak in Wuhan, China. 14 Jan 2020. Volume 91P264-266. International Journal of Infectious Diseases.
  6. George Tetz and Victor Tetz. SARS-CoV-2 Prion-Like Domains in Spike Proteins Enables Higher Affinity to ACE2. 29 March 2020. Preprint. Awaiting peer review.
  7. Alexandra C. Walls, et al., Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. 9 March 2020. Cell.
  8. Author links open overlay panelB.Coutard et al., The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. 2020. AntiViral Research.
  9. Bedford T, Neher R, Hadfield N, Hodcroft E, Ilcisin M, Müller N. Genomic analysis of nCoV spread: Situation report 2020-01-30
  10. An Open letter from our Chairman and CEO.
  11. http://fftc.fujifilm.co.jp/en/avigan/index.html
  12. https://www.reuters.com/article/us-health-coronavirus-fujifilm/fujifilm-shares-jump-15-on-china-coronavirus-drug-trial-boost-idUSKBN215025
  13. https://newsroom.regeneron.com/index.php/news-releases/news-release-details/regeneron-announces-important-advances-novel-covid-19-antibody
  14. NIH clinical trial of investigational vaccine for COVID-19 begins.

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4 Responses

  1. Edwin Portalatin says:

    Great article! Very informative! Thanks!

    1+
  2. Tom Bell says:

    Very well worth reading and informative helpful to realise what we have deal with

    1+

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