Masked kids at science camp. Photo by Rickinasia, Wikimedia Commons
(Click on the following link to listen to an audio version of this blog … COVID 19 Fundamentals and Updates
Back in March, 2020, I wrote an essay summarizing what we knew about the virus that causes the disease COVID-19. That virus is SARS-CoV2. Since I wrote that inital essay about SARS-CoV2 and COVID-19, 604 million people around the world have contracted the virus, and 6.5 million of these people have died. Although these numbers are staggeringly large most experts agree that they are gross underestimates of both the number of cases of COVID-19 and the number of deaths. Humankind and its social and economic institutions have been severely impacted by this virus. Each one of us has had our lives disrupted, put on hold and changed by SARS-CoV2.
There are seven “coronaviruses” known to affect humans. Four of these viruses infect cells in the upper respiratory tract and cause what we call the “common cold.” On average, people in North America get infected with these four, common cold corona viruses and “catch” colds three time a year. The other three corona viruses cause much more serious, respiratory illnesses than the common cold coronaviruses. These three viruses are the “SARS-CoV” virus which emerged in 2003, the “MERS-CoV” virus which emerged in 2012 and SARS-CoV2 which emerged in late 2019.
The outbreaks of both SARS and MERS were contained and although the death rates for people who contracted these viruses was quite high (SARS had a death rate of 10%, MERS had a death rate of 23% (for comparison, SARS-CoV2 has a death rate between 1 and 2% and the common flu virus (which is an entirely different virus from the corona viruses) has a death rate of 0.2%), their overall impacts on human populations were limited. SARS-CoV2, though, was not contained, and it rapidly spread around the world causing the pandemic disease COVID-19.
Basic coronovirus structure, Photo by SPQR10. Wikimedia Commons
The name “corona” was given to these viruses because of the distinctive “spike” proteins that project off of the spherical “body” of the virus. These spikes make the virus look like a crown or like the corona of the sun. There are approximately 74 surface spikes projecting off of each virus particle. The virus is between 60 and 140 nanometers in diameter (a nanometer is one trillionth of a meter in length, so these viruses are very small, indeed!), and it has an outer, structural envelope that is made up of cell membrane fragments of old host cells and three types of proteins (Membrane Proteins, Envelope Proteins and the Spike Proteins). All of these proteins are synthesized by the highjacked metabolic systems of the host cell under the control of the virus’s genetic information.
Inside the protective envelope is the active part of the virus: its nucleic acid strand. The information-encoding nucleic acid in SARS CoV2 is a single-stranded RNA molecule that is 29,811 nucleotides long. This RNA molecule is wrapped in its own protein layer (the Nucleocapsid Proteins) within the protected space of the envelope.
The viral RNA molecule contains the information for the synthesis of 29 proteins. Four of these proteins are the Membrane, Envelope, Spike and Nucleocapsid proteins we have already mentioned. These four proteins are called the Structural Proteins. The remaining 25 proteins include the Non-Structural Proteins which are formed from precisely partitioned pieces of two very long polyproteins that are directly synthesized by translation of the viral RNA, and a smaller set of independently translated proteins called the Accessory Proteins.
The Non-Structural Proteins regulate how the virus replicates in the host cell and also how it assembles copies of itself. They also play a role in helping the virus avoid detection by the host organism’s immune system. These proteins, then, could be said to run the metabolic machinery of the virus in the host cell. The Accessory Proteins (which are not required by the virus for its replication under laboratory conditions) are thought to interact with the host organism’s immune system and may, therefore, play an important role in the transmissibility and pathogenicity of the virus.
SARS-CoV2. Figure by CDC, Public Domain
A great deal of research has been directed at the structure and functioning of the Spike Proteins. These are the proteins that the virus uses to attach to receptors on the surface of the cells of its host. The Spike Proteins of SARS-CoV2 are 80% similar in their amino acid composition and sequences to those of the original SARS virus. Each spike is made up of two principle subunits: the distal polypeptide section called “S-1,” and the more proximal polypeptide section called “S-2.” Each spike contains three S-1 polypeptides that are attached to two S-2 polypeptides.
The distal-most amino acid sequence of the S-1 Spike Protein of the SARS-CoV2 virus attaches to specific protein receptors on the external, cell membrane of mucosa cells of the respiratory tract. This attachment occurs after the S-1 subunit has separated from the S-2 (this separation generates an enzyme that catalyzes the attachment). In SARS-CoV2, common, human, cellular enzymes (like “furin”) that are present in the extracellular environment around potential host cells, speed up the separation of the S-1 and S-2 subunits and make the virus more likely to attach to the potential host cell. They may even make the virus to host cell attachment stronger. This mutational feature of SARS-CoV2 is thought to be one of the key features that makes this variant of the virus so infectious for human beings!
The surface receptor proteins that SARS-CoV2 bind with include the very common and very abundant ACE2 (“angiotensin converting enzyme 2”) protein. ACE2’s are found on many types of body cells but are extremely abundant on cells lining the respiratory tract. At first it was though that ACE2 was the exclusive receptor for SARS-CoV2, but it has been determined that a number of other cell surface receptors can also serve as attachment sites for the virus (including N(APN) (“aminopeptidase”), Neuropilin, CD4 and DPP4 (“dipeptidyl peptide 4”)).
Corono viruses. Photo by CDC.Public Domain
Cells in any organ of the body that have any of these cell membrane receptor proteins may get infected with SARS-CoV2 and then be damaged both by the viruses themselves and also by the body’s vigorous immune response to the presence of the virus. These widespread receptors may explain the incredible array of potential organ involvement that can be seen in COVID-19 patients and also many of the observations of the Long Covid Syndrome.
When the virus binds to the receptor protein, enzymes are activated which allow the viral envelope to fuse with the phospholipid cell membrane of the host cell. This allows the virus to release its genetic material into the cytoplasm of the cell. The viral RNA then takes over the metabolic systems of the host cell and initiates very active translation (“protein synthesis”) of the virus’s 29 proteins. The Non-Structural Proteins of the virus then stops the host cell from synthesizing its own proteins and changes it over to exclusively make the proteins and then the assembled copies of the virus. Huge numbers of the virus are made in an infected cell.
SARS-CoV2 viruses emerging from a human cell. Photo by NIAD, Wikimedia Commons
The viral load in the cell results in the cell’s death with the subsequent release of the newly synthesized viruses along with a mix of cellular debris. Immune system reactions to the presence of these shed viruses and to released cellular debris generates the first symptoms of COVID-19 (sore throat, dry cough, fever, etc.). The newly released viruses, then, continue to spread down respiratory tract infecting more and more cells causing more and more severe symptoms. Infection of the cells in the lungs (bronchioles and alveoli) can lead to pneumonia.
NOTE: about 80% of individuals infected with the original SARS-C0V2 virus had mild symptoms (infection stayed in the upper respiratory organs (it behaved like a common cold!). The remaining 20% of infected individuals, though, got lower respiratory tract infections with much more serious symptoms, and approximately 2% of individuals infected with the original SARS-CoV2 virus died.
A person infected with the COVID-19 virus will cough and sneeze due to mucous membrane irritations caused by the virus and the released cellular debris. These sneezes and coughs will expel tiny droplets of water that are packed with viruses. These droplets can travel about 6 feet from the infected individual. This six-foot distance is the spacing advocated by the CDC and the National Institute of Health with the idea of keeping one’s “social distance” when out in public.
Sneeze and aerosol particles. CDC, J. Gathany. Wikimedia Commons
It was initially thought (or, maybe, it was initially hoped) that these expelled droplets were relatively large and, so, did not stay suspended in the air for very long. Surface persistence and transmission of the virus, then, was initially considered to be the prime mechanism of viral spread. Droplets landing on plastic or stainless steel surfaces were shown to remain viable for 2 to 3 days. Droplets landing on a more porous surface (cardboard) remained viable for 24 hours. Droplets landing on fabric surfaces (like blankets?) were said to remain viable for even shorter periods of time according to the Mayo Clinic (although little experimental data supported this).
So, surface cleaning, hand washing etc. were initially thought to be the key steps to control the spread of the SARS-CoV2 virus. Unfortunately, though, microdroplets ladened with viruses that remained suspended for many hours were noted in both laboratory experiments and in active, social sites. The lingering air-transmission of SARS-CoV2 was, therefore, confirmed. All that surface disinfecting (scrubbing groceries, mail, door knobs and so on) was probably ineffective and unnecessary (but, at least, it gave us something to do!).
(Next week: The “waves” of SARS-CoV2 variants!)