Life Cycle of SARS-CoV-2 Virus
Endocytosis
A key step in COVID-19 pathogenesis is the entry of the SARS‐CoV‐2 virus into the airway epithelial cells; this process employs the cellular mechanisms of endocytosis, and therefore targeting these mechanisms has therapeutic potential for treating COVID-19.
Replication
During the intracellular life cycle, coronaviruses express and replicate their genomic RNA to produce full-length copies that are incorporated into newly produced viral particles.
Exocytosis
Exocytosis is the process in which vesicles containing the virus are secreted/excreted out of the infected cell and back into the host’s airway or bloodstream.
Molecular Art
Inspiration from Professor of Computational Biology and artist David Goodsell
We used David Goodsell’s gorgeously complex illustration of the lifecycle of the SARS-CoV-2 virus as the basis for understanding how our artist Andy Murdock could best represent the hijacking of human cells in stereoscopic 360-degree animation. We did quite a bit of research into this complex process and Goodsell’s watercolors provided the inspiration we needed to be able create animations that could be understood without narration.
But if you’re interested in a little bit of molecular biology (and don’t mind googling the keywords in boldface), here’s what we understand is actually going on as the virus replicates itself inside one of our nasopharynx epithelial cells. (These are the cells that line our nasal cavity and airways.) Above are two versions, with the right-most version color-simplified to make the processes more clear. The area shaded in yellow is outside the cell (in the airway) and the b&w area is within the cell.
The process begins once the virion has been absorbed into the cell through endocytosis. It becomes surrounded by a double-layer membrane as it’s absorbed and converted to a vesicle through a process known as invagination. Once the viral vesicle is invaginated, the RNA it contains leaks into the intercellular cytoplasm. Viral RNA is represented in the illustration as the pink curlicues.
Ribosomes from the endoplasmic reticulum coordinate with the Golgi body and transcribe new viral proteins. The viral RNA carries encoded instructions for the ribosomes to produce a new enzyme called polymerase soon after infection, and this polymerase is what constructs new strands of RNA as part of viral replicase (which controls replication and transcription). SARS-CoV-2 has 29 proteins, the most famous of which is the Spike protein that binds with human ACE2 receptors. Other significant proteins include the Membrane and Envelope proteins, which are structural, and the Nucleocapsid protein which envelopes the virus’s RNA.
The new RNA forms folded capsids that, along with the newly-copied proteins, migrate to the phospholipid bilayer outer membrane of the human cell through exocytosis. Exocytosis uses cellular energy to actively transport bulk molecules (proteins and RNA in this case) to the phospholipid bilayer surrounding the cell and the new virion literally borrows the human cell’s membrane as this budding process organizes all the components into new virions that are released into the pharynx.
The epithelial cell has been severely compromised during this process and deteriorates rapidly, which is the cause of many of COVID19’s symptoms.
This painting shows a cross section through SARS-CoV-2 surrounded by blood plasma, with neutralizing antibodies in bright yellow. The painting was commissioned for the cover of a special COVID-19 issue of Nature, presented 20 August 2020, and is currently in the collection of the Cultural Programs of the National Academy of Sciences.
This painting shows a cross section through a small respiratory droplet, like the ones that are thought to transmit SARS-CoV-2. The virus is shown in magenta, and the droplet is also filled with molecules that are present in the respiratory tract, including mucins (green), pulmonary surfactant proteins and lipids (blue), and antibodies (tan).
This painting depicts a coronavirus just entering the lungs, surrounded by mucus secreted by respiratory cells, secreted antibodies, and several small immune systems proteins. The virus is enclosed by a membrane that includes the S (spike) protein, which will mediate attachment and entry into cells, M (membrane) protein, which is involved in organization of the nucleoprotein inside, and E (envelope) protein, which is a membrane channel involved in budding of the virus and may be incorporated into the virion during that process. The nucleoprotein inside includes many copies of the N (nucleocapsid) protein bound to the genomic RNA.
Discussion Guide
There is no place on Earth that has not been impacted by the microscopic SARS-CoV-2 virus and the ensuing pandemic. Every individual, family, community and nation has responded in their own way, resulting in a few success stories but many failures when it comes to stopping the spread of the virus. Currently, humanity’s ability to collectively find solutions to this crisis is being tested and the fractures within our healthcare, social services and governmental systems are being highlighted as the virus continues to spread with no end in sight. Dr. Josiah Child’s COVID-19 survivor’s story is just one of the millions of firsthand infection experiences to date.
1. Dr. Child was tracking the news from Wuhan, China early on, weeks before the novel coronavirus was named COVID-19 and the spread was declared a pandemic by the World Health Organization (WHO).
When did you first begin tracking the spread of the SARS-CoV-2 virus and what were your initial thoughts and feelings surrounding the news of the Pandemic?
2. Josiah began preparing his emergency departments as soon as he realized the virus was spreading around the world.
At what point did you begin changing your daily behavior in response to the pandemic and what changes did you make?
3. In the early days of the COVID-19 pandemic, the virus was much more mysterious than it is today. Dr. Child was in communication with doctors around the world who were sharing all the available information as they raced to understand how it spread and how to treat infections; all while keeping hospital staff and patients safe.
Where have you been receiving your healthcare guidance during the pandemic and has that changed since it began? Now that we know more about proven preventative healthcare measures like sanitizing hands, wearing masks, physical distancing and not gathering in indoor spaces unless absolutely necessary, do you still have unanswered questions?
4. Despite all the preventive measures Josiah was taking to keep his staff, patients and himself safe within the hospital, he was infected at home by his son Sam who was presymptomatic, and Sam had been infected by his girlfriend who was asymptomatic. Many healthcare workers and the population at large are being infected at home by loved ones who do not know they have the virus.
Do you have a personal connection to anyone who has become sick with COVID-19? If so, please reflect on how they were infected and the ways in which it spread or was contained in their social circle. If you don’t know of anyone who has been infected, why do you think your community of family and friends have avoided the virus?
5. As the virus took hold in Josiah's body, the infection gradually escalated until his family was so worried that they pressured him to go to the hospital. He explains that “I had spent years in hospitals on overnight shifts, 24 hour shifts and I had a kind of PTSD about all the loneliness associated with that, and during the COVID-19 pandemic I knew I was going to be alone.”
Have you been isolated or alone during the pandemic and if so what was your reaction? Have you resisted following healthcare guidance or concern from your family or friends in order to avoid being alone or isolated?
6. Josiah's wife Mary Nell spent years working in Uganda in public health and while driving Josiah to the hospital she shares that “One day I saw a piece of cardboard tacked to a tree that said ‘Ebola 20km from here’ and I thought wow that is great public health messaging and let’s get the hell out of here. I realize with the Covid pandemic that little piece of cardboard is everywhere, there’s no place to go.”
What public health messaging has impacted you? If SARS-CoV-2 is everywhere what steps do you think are needed to stay safe?
7. While Josiah was seriously ill in the hospital his friend and colleague radiologist Steve Abedon reviewed his CT Scans that illustrated the damage in Josiah’s lungs. Josiah shares “When Steve Abedon took me through my CT scan, the care that he took made me feel cared for in some strange way from the inside and it was a very profound feeling.” Personalized care is the foundation of medicine and even though there was very little medical intervention that could be done for Josiah, getting a clear diagnosis can be the first step towards healing.
Have you ever had a disease which didn’t have a clear diagnosis? What was that like for you and how did you deal with it? When you were flying through Josiah’s lungs, what feelings came up for you?
8. As Josiah's family sit on the living room couch and reflect on this illness, Mary Nell ends with “I look back on that time bewildered but with a lot of relief that we are all fine and in some weird way the virus has brought us closer together.”
Have you deepened family connections or friendships during the pandemic? Reflect on any silver lining examples you have experienced.
9. Josiah shares “A hundred years ago, the 1918 Spanish flu pandemic killed almost 700,000 Americans and at least 20 million people worldwide. The extent and depth of the suffering we experienced then has largely been forgotten.”
Do you think the death and suffering of this pandemic is influencing enough people to change their behavior in order to stop the spread of the virus?
10. Josiah thinks “People revolt against wearing masks when they believe they are not sick, but in order to contain the spread of the virus we need to overcompensate and create a sort of religion around wearing masks and social distancing.”
Have you felt like rebelling against wearing a mask and social distancing? How do you feel about others who don’t wear masks?
11. Josiah emphasizes how Dr. Robert Gallo and Dr. Anthony Fauci were the elders he turned to for guidance and shares “Elders in society have always filled this role and I can only imagine that when society faces its next crisis that we who lived on the front lines of this one will be turned to by the men and women on the front lines of the next one for some kind of perspective and I only hope that we can provide that.”
How can we ensure that the lessons of the early days of the pandemic are integrated into our current response? How can we create resilience for the next crisis faced by humanity?
12. At the end of the film Josiah closes by sharing “Honestly I think a combination of desperation and imagination sometimes brings out the best in people. I know I became a physician because handling crisis I thought brought out the best in me.”
What are some examples of how the crisis has brought out the best in you?