Coronavirus aka COVID-19 aka SARS-CoV-2

If you have not yet heard of “the” Coronavirus you must not be paying attention. However, knowing about it does not necessarily mean you are informed about it. There seems to be a lot of misinformation regarding this disease. Perhaps here I can make things a little more clear.

What is colloquially called “The Coronavirus” is a virus of the Coronaviridae family of the sub-family Orthocoronavirinae of the order Nidovirales of the genus Betacoronavirus of the subgenus Sarbecovirus. The species name of the virus has been classified as Severe Acute Respiratory Syndrome-related Coronavirus (SARS-CoV-2) which causes the disease classified as COVID-19, an acronym for COronaVIrus Disease 2019. This species name is due to the fact that its genome has 82% DNA sequence identity with SARS-CoV (what colloquially known as just SARS back in 2003). Coronaviruses are thus named because they appear in a crown shape under electron microsocopy – from the Latin root Coronam, meaning crown.

Evolution of Coronavirus

Coronavirus Evolution

Taxonomy of Coronavirus

Coronavirus Taxonomy

The SARS-CoV-2 virus is in the Betacoronavirus genus, which is 1 of 4 genera of coronavirus – the mammalian species of Alphacoronavirus and Betacoronavirus, and the avian species of Deltacoronavirus and Gammacoronavirus. The Betacoronavirus genus is further broken down into 5 subgenera, with SARS-CoV-2 being of the Sarbecovirus subgenus. There are 7 known human coronaviruses (HCoV), some of which, such as HCoV-OC43, HCoV-HKU1,  HCoV-229E, and HCoV-NL63 are responsible for certain strains of the common cold. More deadly strains, such as SARS-CoV (colloquially known as just SARS) and MERS-CoV (Middle East Respiratory Syndrome Coronavirus), the mortality rates are up to 10% and 35%, respectively.

SARS-CoV-2 Structure

Coronavirus Structure

The SARS-CoV-2 virus contains the outer membrane where the virus was generated. Sticking out of this membrane are glycoproteins called Spike. These Spike proteins associate tightly with the ACE2 transmembrane protein of the human alveolar epithelial cells. This allows the virus to gain entry into the cell.

Coronavirus Entry

The normal physiological function of ACE2 is in the processing of angiotensin (angio, as in the heart (angina, angiogenesis) and tensin, as in causes tenseness), a peptide hormone that controls vasoconstriction (“tenseness” of the blood vessels) and blood pressure (think ACE inhibitors for people with high blood pressure). ACE2 is a type I membrane protein expressed in lungs, heart, kidneys and intestine. Decreased expression of ACE2 is associated with cardiovascular diseases. The peptidase domain (the part of the protein that does the processing of angiotensin) of ACE2 cleaves angiotensin (Ang) I to produce Ang-(1-9), which is then processed by other enzymes to become Ang-(1-7). ACE2 can also directly process Ang II to give Ang-(1-7). This causes blood pressure to increase.

The SARS-CoV-2 Spike protein contains 2 subunits, 1 which allows it to bind with ACE2 and another which allows it to fuse its own membrane with the cellular membrane and thereby giving the viral genome entry into the cell. Once the SARS-CoV-2 virus has gained access into the cell, its positive sense sub-genomic single-stranded RNA can be immediately translated. Lets break down what all these qualifiers to the viral genome mean. The viral genome is RNA, which is different from the DNA that make up the human genome in subtle but important ways. One way is that it is often single-stranded, which in the case of SARS-CoV-2 is the case. Sub-genomic means that multiple proteins can be produced from this single 29,891 nucleotide sequence by skipping over different parts of the sequence when translating or by translating different reading frames. The fact that SARS-CoV-2 is positive sense is why it is immediately ready for translation as soon as it enters the cell – it is structured just like any mRNA produced by our own cells, ready with a 5` cap and 3` poly-Adenine tail.

Coronavirus Replication

Some of the proteins produced by this viral RNA are known only as non-structural proteins (NSPs) and function by blocking the hosts immune response and hijacking the hosts protein synthesis machinery. This is ultimately what causes the pathophysiology of the disease COVID-19.

Based on data from the early cases in Wuhan, the incubation period of the virus is 3 to 7 days and possibly up to 2 weeks. The longest recorded time from infection to symptoms was 12.5 days. This data also showed that this novel epidemic doubled about every 7 days, whereas the basic reproduction number (R0) is 2.2 – on average, each patient transmits the infection to 2.2 other people. The R0 of the SARS-CoV (colloquially known as SARS) in 2002-2003 was about 3.

 

References

Features, Evaluation and Treatment Coronavirus (COVID-19)

Interspecies transmission and emergence of novel viruses: lessons from bats and birds

Structure, Function, and Antigenicityof the SARS-CoV-2 Spike Glycoprotein

ACE2 on NCBI Gene and UniProtKB databases

The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2

Alveolar Epithelial Cells Are Critical in Protection of the Respiratory Tract by Secretion of Factors Able To Modulate the Activity of Pulmonary Macrophages and Directly Control Bacterial Growth

Wikipedia article on Positive-sense single-stranded RNA virus

Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2

Expasy Swiss-Model database entry on SARS-CoV-2 protein structures

Economist article “Understanding SARS-CoV-2 and the drugs that might lessen its power

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