Coronaviruses are a group of viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respiratory tract infections that are typically mild, such as the common cold. Howver,, other forms such as SARS, MERS, and COVID-19 can be lethal.
Coronaviruses comprise the subfamily Orthocoronavirinae, in the family Coronaviridae, order Nidovirales. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size ranges from approximately 27 to 34 kilobases, the largest among known RNA viruses. The coronavirus particles are typically decorated with large (~20 nm), club- or petal-shaped surface projections (the "peplomers" or "spikes"). In electron micrographs this is visualized by spherical particles that create an image reminiscent of the solar corona. The 5' end of the coronavirus genome has a methylated cap and the 3' end has a polyadenylated tail. The viral envelope, obtained by budding through membranes of the endoplasmic reticulum (ER) or Golgi apparatus, contains the S (spike) and M (membrane) virus-specified protein. Glycoprotein S comprises the large surface projections, while M is a triple-spanning transmembrane protein. The phosphoprotein N (nucleocapsid) is another important structural protein, which is responsible for the helical symmetry of the nucleocapsid that encloses the genomic RNA.
Figure 1. Images of the virions of the coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2.
After entry into the host cell, the coronavirus particle is uncoated, and its genome enters the cell cytoplasm. Coronavirus genomes encode a protein called RNA-dependent RNA polymerase (RdRp). This protein allows the viral genome to be transcribed into new RNA copies using the host cell's machinery. The RdRp is the first protein to be made. Once the sequence encoding the RdRp is translated, translation is stopped by a stop codon. This is known as a nested transcript. When the mRNA transcript only encodes one gene, it is monocistronic. Coronavirus non-structural proteins provide extra fidelity to replication, because they confer a proofreading function, which is lacking in RNA-dependent RNA polymerase enzymes alone.
The genome is replicated and a long polyprotein where all of the proteins are attached is formed. Coronaviruses have a protease which is able to cleave the polyprotein. This process is a form of genetic economy, allowing the virus to encode the greatest number of genes in a small number of nucleotides.
Coronaviruses are believed to cause 15 to 30% of all common colds in adults and children. Seven strains of human coronaviruses are known:
- Human coronavirus 229E (HCoV-229E)
- Human coronavirus OC43 (HCoV-OC43)
- Severe acute respiratory syndrome coronavirus (SARS-CoV)
- Human coronavirus NL63 (HCoV-NL63, New Haven coronavirus)
- Human coronavirus HKU1
- Middle East respiratory syndrome-related coronavirus (MERS-CoV)
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019-nCoV, "novel coronavirus 2019" or COVID-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
SARS-CoV-2, previously known by the provisional name 2019 novel coronavirus (2019-nCoV). The virus has close genetic similarity to bat coronaviruses, from which it likely originated. An intermediate reservoir such as a pangolin is also thought to be involved in its introduction to humans. From a taxonomic perspective SARS-CoV-2 is classified as a strain of the species severe acute respiratory syndrome-related coronavirus (SARSr-CoV). To avoid confusion with the disease SARS, the WHO refers to the virus as "the virus responsible for COVID-19" in public health communications.
SARS-CoV-2 is a member of the subgenus Sarbecovirus (beta-CoV lineage B) of the coronaviruses. Its RNA sequence is approximately 30 kilobases in length. The virus is unique among known betacoronaviruses in its incorporation of a polybasic cleavage site. This is a characteristic known to increase pathogenicity and transmissibility in other viruses.
Like other coronaviruses, SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins. The spike protein is responsible for allowing the virus to attach to the membrane of a host cell. Protein modeling experiments on the spike protein of the virus suggests that SARS-CoV-2 has sufficient affinity to the angiotensin converting enzyme 2 (ACE2) receptors of human cells to use them as a mechanism of cell entry. It has been demonstrated that ACE2 receptors could act as the receptor for SARS-CoV-2. Studies have shown that SARS-CoV-2 has a higher affinity to human ACE2 than the original SARS virus strain.
Figure 2. SARS-CoV-2 genome structure
Middle East respiratory syndrome-related coronavirus (MERS-CoV)
MERS-CoV is a species of coronavirus which infects humans, camels and bats. The virus was initially called 2012 novel coronavirus (2012-nCoV) or simply novel coronavirus (nCoV). MERS-CoV was first reported in 2012 after genome sequencing of a virus isolated from sputum samples from a person who fell ill in a 2012 outbreak. MERS-CoV is a new member of the beta group of coronavirus, Betacoronavirus, lineage C. MERS-CoV genomes are phylogenetically classified into two clades, clade A and B. The earliest cases of MERS were of clade A clusters (EMC/2012 and Jordan-N3/2012), and new cases are genetically distinct (clade B)The DPP4 receptor on host cells is responsible for binding of the virus. .
MERS-CoV is distinct from SARS coronavirus and distinct from the common-cold coronavirus and known endemic human betacoronaviruses HCoV-OC43 and HCoV-HKU1. Until 2013, MERS-CoV had frequently been referred to as a SARS-like virus, or simply the novel coronavirus, and earlier it was referred to colloquially on messageboards as the "Saudi SARS".
Over 2,000 cases of MERS have been reported by 2017 with about 600 deaths. Over 180 genomes have been sequenced and nearly all sequences are >99% similar. The genomes can be divided into the clades A and B, with the majority of cases being caused by clade B. Human and camel strains are intermixed suggesting multiple transmission events.
Severe acute respiratory syndrome coronavirus (SARS-CoV)
SARS-CoV is the strain of virus that causes severe acute respiratory syndrome (SARS). This positive-sense, single-stranded RNA virus infects the epithelial cells within the lungs. The virus enters the host cell by binding to the angiotensin converting enzyme 2 (ACE2) receptor. It infects humans, bats, and palm civets. SARS-CoV follows the replication strategy typical of the coronavirus subfamily.
In 2003, studies from samples of wild animals sold as food in the local market in Guangdong, China, found a strain of SARS coronavirus could be isolated from masked palm civets, but the animals did not always show clinical signs. The preliminary conclusion was the SARS virus crossed the xenographic barrier from palm civet to humans. The virus was also later found in raccoon dogs, ferret badgers, and domestic cats. Later, two studies identified a number of SARS-like coronaviruses in Chinese bats. Phylogenetic analysis of these viruses indicated a high probability that SARS coronavirus originated in bats and that the virus spread to humans either directly or through animals held in Chinese markets. Infeted bats do not show any visible signs of disease, but are the likely natural reservoirs of SARS-like coronaviruses. In late 2006, scientists established a genetic link between the SARS coronavirus appearing in civets and humans, confirming claims that the disease had jumped across species.