Coronaviruses have caused a total of 3 pandemics. We have broken down one of peer-reviewed scientific articles that describes the identification of the coronavirus responsible for the current COVID-19 pandemic.
It wasn't our plan to start this chronicle with a post about a deadly virus. We wanted to first address questions related to environmental biology, a topic that we both are more familiar with. However, it didn’t feel like we really had a choice in these unprecedented times when a biological threat changes the very basis of our life. People are getting infected all over the world, stock markets are collapsing, and yet it doesn’t seem like we have enough information about what is really happening. Many “facts” about the new coronavirus delivered by news outlets, social media, and even science oriented organisations are questionable and sometimes misleading.
“Many “facts” about the new coronavirus delivered by news outlets, social media, and even science oriented organisations are questionable and sometimes misleading.”
The purpose of this first in a series of posts about the coronavirus is to trace how this viral outbreak started and to summarize what exactly is currently known about the problem.
Pretty Light Viruses
In the last two decades coronavirus has been responsible for two pandemic events spread across vast regions, SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). Typical clinical symptoms of the infected people include fever, dry cough, headache, and pneumonia. Another outbreak started on December 12, 2019 when the first patient was hospitalized and proceeded to infect 2050 people in China, causing 56 deaths, and 35 people in 11 other countries as of January 26, 2020. A new study published in Nature investigates a possible cause of this outbreak and suggests that a novel coronavirus, probably originated in bats, is a likely candidate.
In this study Wu et al. examined a patient who worked at a seafood market in the city of Wuhan, in the Chinese province of Hubei. He was admitted to the hospital on 12 December 2019 and diagnosed with a serious form of viral pneumonia. The patient tested negative for most of the common respiratory pathogens - influenza virus, Chlamydia pneumoniae, Mycoplasma pneumoniae, and adenoviruses - and had no previous history of illnesses that would make him more likely to get a respiratory infection such as hepatitis, tuberculosis or diabetes.
To detect the cause of the infection, the researchers collected a bronchoalveolar lavage fluid (BALF) sample from the patient, extracted RNA, and performed deep sequencing that resulted in many short pieces of the genome of the virus. They combined (assembled) these short pieces together and built the whole genome of the new virus - later termed SARS-CoV-2 - and compared it to known viral genomes. SARS-CoV-2 clustered together with a virus that was responsible for the global SARS pandemic of 2002–2003 and a few similar coronaviruses which were isolated from bats.
The next step was to estimate the potential of the new coronavirus to infect people. Coronaviruses enter cells via special “spike” proteins which, similar to a key, may have different shapes and fit different “locks” - entry receptor proteins - on the cell surface. The authors compared amino acid sequences of the spike protein from the new 2019-nCoV with those from previously described viruses, which can use the human receptor protein for cell entry. They found significant similarities between them indicating that the viruses may use the same key-lock mechanism. This finding is important because it suggests the potential of the newly discovered virus to infect humans.
Previous studies have shown that bats may host different viruses and a number of proteins from SARS-CoV-2 are very closely related to those from bat coronaviruses. As a result, the authors conclude that bats may act as hosts for SARS-CoV-2. This study provides initial results on the genomic content of the new coronavirus which may be of vital significance in the attempts of the community to stop the spread of the infection.
Glossary
Epidemic - according to the CDC, “Epidemic refers to an increase, often sudden, in the number of cases of a disease above what is normally expected in that population in that area.”
Genetic recombination - exchange of genetic information between organisms.
Genome - a complete set of organism's genes.
Genome assembly - the process of putting back together (assembling) short fragments of DNA derived from sequencing to recreate the target sequence.
Human exopeptidase, angiotensin converting enzyme 2 (ACE2) - simply, a protein on the surface of human cells, in this case specifically cells found in the lung, that SARS-CoV2 can bind to and gain entry into these cells.
Metatranscriptomics - an RNA sequencing approach that gives access to the functional profiles and activity of the complete set of genes (transcripts) from environmental samples (in this case from a mucus sample collected from a hospital patient).
Pandemic - according to the CDC, “Pandemic refers to an epidemic that has spread over several countries or continents, usually affecting a large number of people.”
Pathogen - a microbe, virus or, in general terms, anything that may cause a disease.
Phylogenetics - the study of evolutionary history and relationships between individuals or groups of organisms.
Protein - a molecule made by cells to perform certain functions such as bringing nutrients into the cell or for reading the information stored within the DNA.
Receptor - special structures in cell membranes capable of attaching to certain molecules.
RNA - ribonucleic acid, an essential macromolecule that converts the information stored in the genetic code (DNA) into proteins.
To cluster - to group together based on certain common features.
Virion - a complete virus structure that consists of either DNA or RNA and a protein casing (a capsid).
Scientific Summary
At the end of 2019, Wu and colleagues performed deep metatranscriptomic sequencing on a bronchoalveolar lavage fluid (BALF) sample collected from a forty year old male patient from Wuhan, China and quickly identified the virus that would ultimately cause the third coronavirus pandemic of the 21st century (Wu, F., et al. 2020). This virus has been named the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses (Gorbalenya, A.E., et al. 2020). For clarity we will refer to the virus by its official name throughout this post even though when Wu et al. first published the paper they referred to it as WH-Human 1 coronavirus (WHCV). After confirming that this patient was not infected with other common respiratory infection causing microbes (e.g. influenza, Chlamydia pneumoniae, and Mycoplasma pneumoniae), the researchers performed a metatranscriptomic sequencing analysis and assembled the genome of a virus that is closely related to a bat-derived SARS-like virus (89.1% nucleotide similarity). Their designation of this virus as a coronavirus was further confirmed by the identification and context of genes, as well as its placement in a phylogenetic tree. All coronaviruses have genomes that are organized in a similar fashion, and when viewed under a microscope they have a characteristic spike-like structure on the outside of the virion which is why they are called ‘corona’ (latin for crown) viruses (Su, S., et al. 2016). Within the larger group of coronaviruses just a handful infect humans. The most infamous of these include the viruses responsible for the 2012 MERS (Middle East respiratory syndrome) and 2002 SARS outbreaks (Su, S., et al. 2016).
Genetically, the newly identified SARS-CoV-2 virus clusters with other disease causing SARS viruses isolated from humans - including the 2002 SARS strain - as well as SARS-like bat viruses. The exact placement of the SARS-CoV-2 strain within the phylogeny varies depending on which genes were used to build the tree. This suggests that this virus has undergone some genetic recombination events with other closely related viruses, including those isolated from bats. This type of recombination or swapping of genetic information is not uncommon in coronaviruses (Su, S., et al. 2016). While the authors link a variety of genetic traits between this virus and SARS-like bat-derived strains, they stress that they can’t be certain that this strain did originate in bats. The authors did however determine that the receptor-binding domain of the SARS-CoV-2 spike protein (the characteristic surface structure mentioned previously) was most closely related to SARS-CoVs and SARS-like CoVs that use a human exopeptidase, angiotensin converting enzyme 2 (ACE2) for entry into human cells. Similar results were found when they predicted the structure of this protein.
This was one of the first peer-reviewed articles that identifies and phylogenetically analyzes the virus responsible for the current COVID-19 pandemic that has much of the world in lock down and practicing social distancing measures. Researchers around the world are tirelessly working toward a vaccine and better understanding of this novel virus.
Works Cited
Wu, F., Zhao, S., Yu, B. et al. A new coronavirus associated with human respiratory disease in China. Nature; (2020). https://doi.org/10.1038/s41586-020-2008-3
Gorbalenya, A.E., Baker, S.C., Baric, R.S. et al. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol; (2020). https://doi.org/10.1038/s41564-020-0695-z
Su, S., Wong, G., Shi, W. et al. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol.; (2016). doi: 10.1016/j.tim.2016.03.003.
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