What do we know about Coronaviruses and the SARS-CoV-2 Virus?
Ashly Pavlovsky, PhD and Zachary Moore, PhD
The ongoing human COVID-19 (Coronavirus disease 2019) pandemic is the result of the rapid global spread of a novel virus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2), which was first detected in the Hubei province of China in December 2019.1 Since its emergence, there have been over 2,500,000 confirmed cases of COVID-19 with more than 180,000 deaths globally (as of April 23, 2020), far exceeding the combined overall incidence and mortality of the previous SARS-CoV-1 and MERS-CoV (Middle East respiratory syndrome coronavirus) outbreaks in 2002/3 and 2012, respectively.2,3 This blog series will provide an overview of the virology, epidemiology, management, and public health implications of the SARS-CoV-2 outbreak.
A Brief Overview of Virology
Viruses are sub-microscopic pathogens that infect living cells and hijack their cellular machinery to create copies of themselves. A virion, or single viral particle, is composed of genetic material, either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), encapsulated within a protein coat (capsid) that may or may not be surrounded by a lipid envelope.4 Because viruses cannot replicate on their own and lack essential cellular structures, they are not considered truly living organisms, and are classified instead as “biological entities.”
The category of viruses is the most abundant and diverse in all of biology, exhibiting a high level of genetic and structural diversity across species.4 They can be generally categorized into groups based on the types of organisms they infect (animals, plants, fungi, protists, bacteria, or archaea) and the molecular makeup of their genetic material (double stranded or single stranded, DNA or RNA, and positive- or negative-stranded).5
The coronavirus family, Coronaviridae, is composed of large, enveloped, positive single-stranded RNA (+ssRNA) viruses that infect various mammals and birds, typically resulting in respiratory or gastrointestinal disease.6 Compared to other RNA viruses, coronaviruses have large genomes, around 30kb, that are bound in a helical structure by nucleocapsid phosphoproteins. The helical nucleocapsid is surrounded by a lipid membrane studded with different glycoproteins described as the envelope, membrane, and spike proteins.7 These spikes give coronavirus a “crown-like” appearance, which resulted in their being named after the Latin word for “crown,” or “corona.” During infection, the spike protein binds to a specific receptor on the host cell’s surface which then enables the entry of the virion into the intracellular space, where it can replicate.8 Most members of the Coronaviridae family display a high degree of host species specificity which is largely attributed to the unique amino acid sequence of the receptor binding domain (RBD) of the spike protein.8
Some coronaviruses infect birds, while others commonly infect mammals.9 Although various species have been identified in a rodents and other mammals, most lineages are thought to have originally derived from bats based on the vast diversity of coronaviruses sampled from their populations. 9-11 These viruses may be transmitted to other susceptible mammals via “zoonotic transfer,” which describes the transmission of a virus from an animal source to humans which can occur directly from the natural host or through an intermediate host such as a domesticated animal.12
To date, there are seven known coronaviruses that can infect humans and cause disease, four of which are endemic, and thought to be the cause of up to 20% of common cold infections in humans.9
The other three known human coronaviruses have emerged during the 21st century as novel, highly pathogenic viruses: SARS-CoV-1, MERS-CoV, and SARS-CoV-2.3 Unlike their endemic counterparts, these viruses have caused alarmingly high morbidity and mortality in human populations. The severe acute respiratory syndrome (SARS) pandemic took place from 2002–2003 and resulted in a total of 8437 reported cases and 813 deaths across 27 countries.13 The virus that was responsible for the disease, SARS-CoV-1, emerged in Guangdong province, China in 2002.13 It is hypothesized that SARS-CoV-1 originally derived from viral recombination events in bats and was then transmitted to palm civets at a live-animal market in China where zoonotic transmission occurred.14
MERS-CoV was first isolated in 2012 from a man in Saudi Arabia who died of acute pneumonia and renal failure. Since then, a number of small outbreaks have occurred accounting for more than 2000 confirmed infections across 27 countries resulting in more than 700 deaths.15 MERS-CoV is likely to have emerged through recombination events between various coronaviruses infecting both bats and camels, and then transmitted to humans through direct contact with infected camels.12
The COVID-19 Virus
In December of 2019, another novel pathogenic coronavirus emerged in China. The first cases of the disease it causes, COVID-19, were described in several patients who were admitted to the Wuhan Jin Yin-Tan Hospital for severe acute pneumonia.16 The virus that was isolated from the patients’ samples was sequenced and found to share 79.6% sequence homology with SARS-CoV-1 and 96% sequence homology with a known coronavirus that is found in horseshoe bat populations in China (BatCoV RaTG13).16 Based on phylogenetic and taxonomic classifications, the Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (ICTV) determined the official name for the novel virus, SARS-CoV-2.17
To date, no direct source for zoonotic transmission of SARS-CoV-2 has been identified; however, the genetic evidence suggests that a viral ancestor of SARS-CoV-2 originated from a natural bat reservoir. Interestingly, the SARS-CoV-2 spike protein is more similar to viruses found in Malayan pangolins than viruses found in bats, which suggests that a recombination event between viruses from different sources may have occurred during its evolution.18 Possibly, the virus underwent a series of animal and/or human transmissions that resulted in various recombination and evolution events resulting in its unique motifs.19 More investigation of this virus will be no doubt be forthcoming, and future studies will provide additional clarity regarding the evolutionary origins of SARS-CoV-2.
- Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England) 395, 497-506, doi:10.1016/s0140-6736(20)30183-5 (2020).
- Johns Hopkins University Coronavirus Resource Center, <https://coronavirus.jhu.edu/map.html>
- Park, M., Thwaites, R. S. & Openshaw, P. J. M. COVID-19: Lessons from SARS and MERS. European Journal of Immunology 50, 308-311, doi:10.1002/eji.202070035 (2020).
- Simmonds, P. & Aiewsakun, P. Virus classification – where do you draw the line? Arch Virol 163, 2037-2046, doi:10.1007/s00705-018-3938-z (2018).
- Lefkowitz, E. J. et al. Virus taxonomy: the database of the International Committee on Taxonomy of Viruses (ICTV). Nucleic Acids Res 46, D708-d717, doi:10.1093/nar/gkx932 (2018).
- Kuo, L., Godeke, G. J., Raamsman, M. J., Masters, P. S. & Rottier, P. J. Retargeting of coronavirus by substitution of the spike glycoprotein ectodomain: crossing the host cell species barrier. J Virol 74, 1393-1406, doi:10.1128/jvi.74.3.1393-1406.2000 (2000).
- de Wit, E., van Doremalen, N., Falzarano, D. & Munster, V. J. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 14, 523-534, doi:10.1038/nrmicro.2016.81 (2016).
- de Wilde, A. H., Snijder, E. J., Kikkert, M. & van Hemert, M. J. Host Factors in Coronavirus Replication. Curr Top Microbiol Immunol 419, 1-42, doi:10.1007/82_2017_25 (2018).
- Corman, V. M., Muth, D., Niemeyer, D. & Drosten, C. Hosts and Sources of Endemic Human Coronaviruses. Adv Virus Res 100, 163-188, doi:10.1016/bs.aivir.2018.01.001 (2018).
- Vijaykrishna, D. et al. Evolutionary insights into the ecology of coronaviruses. J Virol 81, 4012-4020, doi:10.1128/jvi.02605-06 (2007).
- Woo, P. C. et al. Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus. J Virol 86, 3995-4008, doi:10.1128/jvi.06540-11 (2012).
- Cui, J., Li, F. & Shi, Z. L. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 17, 181-192, doi:10.1038/s41579-018-0118-9 (2019).
- Zhong, N. S. et al. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s Republic of China, in February, 2003. Lancet (London, England) 362, 1353-1358, doi:10.1016/s0140-6736(03)14630-2 (2003).
- Woo, P. C., Lau, S. K., Huang, Y. & Yuen, K. Y. Coronavirus diversity, phylogeny and interspecies jumping. Exp Biol Med (Maywood) 234, 1117-1127, doi:10.3181/0903-mr-94 (2009).
- Chafekar, A. & Fielding, B. C. MERS-CoV: Understanding the Latest Human Coronavirus Threat. Viruses 10, doi:10.3390/v10020093 (2018).
- Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270-273, doi:10.1038/s41586-020-2012-7 (2020).
- Coronaviridae Study Group. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 5, 536-544, doi:10.1038/s41564-020-0695-z (2020).
- Andersen, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C. & Garry, R. F. The proximal origin of SARS-CoV-2. Nature Medicine, doi:10.1038/s41591-020-0820-9 (2020).
- Cagliani, R., Forni, D., Clerici, M. & Sironi, M. Computational inference of selection underlying the evolution of the novel coronavirus, SARS-CoV-2. J Virol, doi:10.1128/jvi.00411-20 (2020).