An Insight on Coronavirus: The Structure & Viral Replication

"Our greatest enemy is not the virus itself. It's fear, rumors and stigma. And our greatest assets are facts, reasons and solidarity." 

~ Dr. Tedros Adhanom Ghebreyesus, WHO Director-General 

The pandemic COVID-19 is a Severe Acute Respiratory Syndrome (SARS) caused by novel CoronaVirus-2, SARS-CoV-2, which is transmitted mainly by contact with infectious person or material; and is characterized by symptoms of fever, cough, common cold, shortness of breath and may progress to pneumonia/respiratory failure. It is declared 'Pandemic' by the World Health Organisation since the outbreak or prevalence of the disease is widespread across the continents of the world. 

There is a need to understand the structure and function of the virus in order to comprehend and correlate the process of infection and method of recovery in the human body. This further helps in identification of symptoms, cause of death and preparation of vaccine or a medicine for the disease.  

STRUCTURE OF CORONA VIRUS

The Virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. The Host/Host Cell is a living cell invaded or is capable of being invaded by an infectious foreign particle like Virus. 

• The Corona Virus is a positively sensed single stranded mRNA, class 4, with genome enveloped lipoprotein. The nucleo capsid of the virus has an exceptionally, helical symmetry in this virus. 
• The lipoprotein of the Virus which makes up the envelope is made of lipids, derived from the host cell and protein synthesized by the viral genome in the host. 
• The Corona Virus has different types of proteins that are crucial in the structure and infection: Spiked (S) Proteins - helps in the attachment of the virus to the receptor of the host cell and virion fusion; Membrane (M) Protein - provides the viral envelope it's shape; Envelope (E) Protein - involved in the aspects virus' life cycle.The Membrane Protein and Envelope Protein play an important role in the assembly of viral genome & capsid, budding, envelope formation and pathogenesis.
• The Spiked Proteins projects outwards from the membrane and creates a rim-kind-of structure around the membrane. When observed under the electron microscope the rim formed by the spiked proteins looked like the Corona of the Sun (outer most atmosphere of the Sun), therefore it is named as 'CoronaVirus'. 

VIRAL REPLICATION

The action mechanism of corona virus begin as it surpasses the first line of defense in the ingestion process from eyes/nose/mouth and reaches the lungs. The body's immune system is the central node defense mechanism to protect the body against the attack of virus. However, the attack is prevalent when - (a) Dosage of virus of high and strong; (b) lowered immune system or immuno-compromised patients.

Here is an example explaining the viral attack of COVID-19 in the lungs:

 An enzyme, Angiotensin Converting Enzyme -2 (ACE-2) is present on the epithelial cells of the alveoli in the lungs. The spike proteins binds to the ACE-2 enzyme present on the alveolar epithelial cells. Another protease TMPRSS2 (Transmembrane Protease, Serine-2) cleaves a part of spike protein and activates the Corona Virus. Due to the cleavage, the genome envelope fuses with the alveolar cell membrane and virion is taken inside the cell by a process of endocytosis.

Note:- Endocytosis is a cellular process of taking a substance into the cell. The substance to be internalized is surrounded by an area of cell membrane, which buds off inside the cell to as a vesicle containing ingested material. 

The entry of the virus into the host cell occurs when the envelope fuses with the membrane of endosome vesicle which has been taken up, releasing the RNA into the cytoplasm of the host cell. The viral RNA uses host ribososmes and enzymes for translating the mRNA into two forms - Viral Protein & in replication of RNA. The newly synthesized RNA and proteins assemble in the Golgi Apparatus of the host cell. After assembly the virus is released from the cell. So the virus multiples in the host cell making it "Factories of COVID-19", leaves the cell after replication through the process of excytosis and further infects the other cells in the vicinity. During this process it evades the immune system, leaving it confused and causes pathogenesis of the immune system. The pathogenesis of the SARS-Cov-2 on immune system leads to pneumonia that decreases the partial pressure of oxygen in the blood cells leading to a condition called Hypoxemia, oxygen deficiency in the cells resulting death of cells.

The Corona Virus gains entry into the cells which have ACE-2 enzyme making it responsible for Tissue Tropism - the cells and tissues of a host support the growth of a particular virus or bacterium. Therefore specific organs which contain ACE-2 enzyme are targeted, to name a few:

• Lungs - targets alveolar epithelial cells leading to cough, cold , shortage of breath, soar throat etc. 
• Small Intestine - targets inner epithelial cells of the intestine leading Gastrointestinal (GI) symptoms like vomiting, nausea, diarrhea, abdominal discomfort, etc. 
• Heart - targets cardiac epithelial cells resulting in palpitations, chest tightness, etc. 
• Liver - it is observed that the death of SARS-Cov-2 infected patients was due to liver failure.

The SARS-CoV-2 has 10-20% more affinity towards ACE-2 enzyme than any other SARS virus, therefore making it more severe and easy to spread into an outbreak - an epidemic now turned into a pandemic. 

The preliminary physiological study of the novel CoronaVirus has opened avenues for prevention, precaution, treatment and forthcoming invention of testing kits, vaccines and medicines.