This article describes the life cycle of Coronavirus (COVID-19) in six simple steps. It also discusses the role of spike (S) protein of the SARS-CoV-2 virus and the role of Angiotensin-converting enzyme 2 (ACE2) receptors of the host cell in spreading the viruses. This understanding can help to develop suitable drugs and antibodies to counter the viruses.
How the Virus Spread
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spreads primarily through droplets (respiratory secretions) and close person-to-person contact. When a person talks, coughs or sneezes, there are droplets. These droplets spread the virus. It also spreads when a person touches a surface or object that has the virus on it, then touches their eyes, nose, or mouth. Study found that people touched surfaces and their mouth or nose 3 to 4 times per hour. Hence, hand washing is really vital to stop coronavirus.
Spread of Coronavirus through droplets
Life Cycle of COVID-19 (SAS-CoV-2)
After the virus enters into the body, it binds to primary target cells that express abundant virus receptor, the angiotensin-converting enzyme 2 (ACE2), including pneumocytes and enterocytes in the respiratory system, lung, intestine, kidney, and blood vessels. The virus enters and replicates in these cells. The matured virions are then released to infect new target cells. Research has shown that ACE2 allows SARS-CoV-2 to infect human cells. The causative SARS-CoV-2 virus attaches to cells by binding its outer “Spike” proteins to a receptor protein ACE2.
The life cycle of coronavirus (SARS-CoV-2) has six key stages: Attachment, Penetration, Uncoating, Biosynthesis, Assembly and Release. During attachment and penetration, the Covid-19 virus attaches itself to a human host cell and injects its genetic material (RNA) into it. During uncoating, replication, and assembly, the viral RNA express itself into the host cell's genetic material and induces it to replicate the viral genome.
The Life Cycle of Coronavirus (COVID-19) SARS-CoV-2
The Spike Protein (S-protein) of the Virus:
This protein mediates receptor binding and membrane fusion. Spike protein contains two subunits, S1 and S2. S1 contains a receptor binding domain (RBD), which is responsible for recognizing and binding with the cell surface receptor. S2 subunit is the "stem" of the structure, which contains other basic elements needed for the membrane fusion. The spike protein is the common target for neutralizing antibodies and vaccines. It’s been reported that COVID-19 can infect the human respiratory epithelial cells through interaction with the human ACE2 receptor.
Spike Protein S Protein of SAS-CoV-2 Virus
Angiotensin-Converting Enzyme 2 (ACE2) of Host Cells
Angiotensin-converting enzyme 2 (ACE2) is an enzyme within the RAS that is expressed on the cell surface of type 2 alveolar epithelial cells in the lungs, blood vessels, kidney, and intestine, as well as on cells in many other tissues. It also acts as the receptor for the SARS-CoV-2 spike protein, through which the virus gains entry to host cells.
SARS-CoV-2 S-Protien binding to ACE2
Top Twenty COVID-19 Medicines Under Research:
- Chloroquine
- Hydroxychloroquine
- Human Immunoglobulin
- Interferons
- Arbidol
- Remdesivir
- Oseltamivir
- Favipiravir
- Carrimycin
- Methylprednisolone
- Bevacizumab
- Thalidomide
- Vitamin C
- Pirfenidone
- Bromhexine
- Fingolimod
- Danoprevir
- Ritonavir
- Darunavir
- Cobicistat
- Lopinavir
- Xiyanping
Conclusion:
The roles of S protein in receptor binding with ACE2 and membrane fusion shows that vaccines based on the S protein could induce antibodies to block virus binding and fusion or neutralize virus infection. S protein has therefore can be selected as the most important target for vaccine and anti-viral development.
The article explains the life cycle of the SAS-CoV-2 virus and the binding mechanism of S protein of virus and the ACE2 of the host cells. It also explains the top twenty drugs for COVID 19, under research and development.
References:
1. South, A.M., Tomlinson, L., Edmonston, D. et al. Controversies of renin–angiotensin system inhibition during the COVID-19 pandemic. Nature Review Nephrol (2020). https://doi.org/10.1038/s41581-020-0279-4, Published03 April 2020.
2. Lei Fang, George Karakiulakis, Michael Roth, Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?, The Lancet, Respiratory Medicine, Published Online, March 11, 2020, https://doi.org/10.1016/S2213-2600(20)30116-8.
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