SARS-CoV-2 is 94% similar to SARS-CoV in its genetic sequence, but its spike (S) protein is less than 75% similar to that of SARS-CoV. It is an enveloped beta coronavirus 2b (lineage) consisting of a single strand of RNA (ss RNA), 29,891 nucleotides in size in coding for 9,860 amino acids.

It has four structural proteins:

S protein - Spike Protein. Responsible for binding with the host cell’s ACE2 receptor

• S1 Domain: Constitutes the Receptor Binding Domain (RBD), which interacts with the ACE2 membrane bound enzyme on the host cell surface

• S2 Domain: Virus-host cell fusion and entry

M protein - Membrane Protein

E protein - Envelope Protein

N protein - Nucleocapsid Protein

It is the virus responsible for the current infection COVID-19 (Coronavirus disease 2019). The genome was first mapped January 10, 2020.

There are thus far 6 known genotypes (I-VI). Current data suggests that the virus originated from zoonotic origin.

The most genetically similar known virus is a bat coronavirus (BatCoV-RaTG13) from the bat species Rhinolophus affinis, which is 96.7% identical overall to SARS-CoV-2, but its S protein RBD, which has six amino acids, is not similar.

Malayan pangolins (Manis javanica) also have a coronavirus species similar to SARS-CoV-2, but not as similar to those of the bat coronavirus, however their RBD is nearly identical to SARS-CoV-2. A recent study isolated a coronavirus from 17/25 Malayan pangolins (pangolin CoV), which showed 100% identity of amino acids to the E protein, 98.6% to the M protein, 97.8% to the N protein, and 90.7% to the S protein of SARS-CoV-2. Most importantly, the RBD of the S protein was nearly identical, with only a single different amino acid, therefore suggesting that Malayan pangolins could have been the intermediate host between bats and humans.

Another theory of the genesis of SARS-CoV-2 is that there could have been a previous form of the virus which was transmitted to humans from a zoonotic source, which then eventually mutated into SARS-CoV-2 via undetected inter-human transmission.

ACE2 Receptor

An enzyme protein receptor found on the outer surface of certain cells in humans and other animals. In humans, most commonly found in the heart, blood vessels, kidney, testes, respiratory system, liver, intestine, brain, bladder, and esophagus. SARS-CoV-2 has a ten percent higher ability to bind to the ACE2 receptor compared to SARS-Co-V, resulting in a far more efficient infection rate.

The ACE2 receptor has protective effects in the organ systems that it is present in.

• Respiratory System: 83% are expressed on AT2 cells (Type II alveolar apical epithelial cells)

  • Comorbidities, such as Chronic Obstructive Pulmonary Disease (COPD), are associated with lower levels of ACE2 receptors, therefore decreasing the natural protective effects, and making patients more susceptible to more severe COVID-19 disease.

• Cardiovascular System: ACE2 helps naturally decrease blood pressure.

  • Patients with hypertension have decreased ACE2 receptors in their blood vessels and kidneys, therefore having less protection of these organs and are more at risk of severe COVID-19 disease.

• Endocrine System: ACE2 helps normal pancreatic cells to produce insulin

  • Patients with diabetes mellitus have decreased ACE2 receptors in the pancreas, and therefore increasing their risk of severe COVID-19.

  • Diabetic patients also have decreased ACE2 in the kidneys, increasing their risk of diabetes nephropathy.

There seems to be a clear association between the organ systems that are naturally rich in ACE2 and those affected by COVID-19. Those patients that have comorbidities affecting these organs are at the highest risk of severe COVID-19 infection.