Contrary to circulating conspiracy theories and myths of COVID-19 being a synthetically made virus that was created in a laboratory and then unleashed to cause a global crisis, a recent study published in the journal Nature Medicine helps lay these claims to rest.
The new human COVID-19 virus belongs to the coronavirus (CoV) family. These viruses can cause different illnesses ranging from the common cold to more serious respiratory tract infections.
Coronaviruses represent a large family of viruses that are primarily found in birds and mammals such as bats, camels and cats. Some of the more recent and virulent strains of human coronaviruses arose from the evolution and transfer of the viruses from some of these animals. Viruses evolve through natural selection pressures that genetically transform them so that they can infect a new target host of a different species. Diseases that are transmitted from animals to humans are called zoonotic diseases.
There are now seven known coronaviruses that affect humans, of which the Severe Acute Respiratory Syndrome (SARS-CoV-1), the Middle East Respiratory Syndrome (MERS-CoV) and now Coronavirus Disease of 2019 (COVID-19), also called SARS-CoV-2, are derived from animal coronaviruses and can cause serious illness in humans. The other human coronaviruses (HKU1, NL63, OC43 and 229E) cause milder symptoms.
Coronavirus strains similar to human SARS-CoV-1 are largely found in bats, which likely serve as the primary host reservoir of the viruses. Coronaviruses similar to SARS-CoV-1 are also found in pangolins. Transmission of these viruses to humans can occur from a primary host or through a secondary, intermediate host.
Related: COVID-19 Outbreak Coverage
Coronaviruses have an outer protein coat that has distinctive structural projections on its surface known as spike (S) proteins, which give the virus a crown-like appearance. The name “corona” is Latin for “crown,” which is why the viruses were given the name “coronavirus.” The spike protein functions in the binding of the virus to host cells.
To help decipher the origin of the COVID-19 coronavirus, investigators of the Nature Medicine paper conducted comparative genomic analysis to compare the genome of COVID-19 to other strains of both human and animal coronaviruses. They found that the virus is closely related to human SARS-CoV-1, as well as specific bat and pangolin coronavirus strains.
“By comparing the available genome sequence data for known coronavirus strains, we can firmly determine that SARS-CoV-2 [COVID-19] originated through natural processes,” said Kristian Andersen, Associate Professor of Immunology and Microbiology at the Scripps Research Institute in California and lead author of the study.
It was found that COVID-19, however, differs from SARS-CoV-1 and the animal viruses based on two main features: 1) the receptor-binding domain (RBD), which helps viruses attach to host cells and 2) the presence of a novel cleavage site, which plays a role in entering cells. Both are located in the spike protein of the virus.
The RBD is the most variable part of the virus across the different family members. The RBD specifically binds to an enzyme on host cells called angiotensin-converting enzyme 2 (ACE2). There are six amino acids in the RBD that have been shown to be critical for ACE2 binding.
Through their analysis, the study researchers found that five of the six RBD amino acids differ between COVID-19 and SARS-CoV-1. Based on structural and biochemical studies of the binding properties of these amino acids and the overall RBD of other coronaviruses, it appears that the amino acid changes, i.e. mutations, in COVID-19 may allow its RBD to bind with higher affinity to ACE2 on human cells.
Another significant defining feature of COVID-19 is the presence of a polybasic cleavage site located at a junction between two different spike proteins. This site is not found in SARS-CoV-1. Cleavage of this site by enzymes is thought to play a role in viral infectiousness as well as host range i.e. transmission between hosts.
Both RBD mutations and the addition of a new cleavage site in the spike protein are thought to enhance the ability of COVID-19 to infect human cells, which is perhaps why the virus is highly contagious. It is believed that these changes may have occurred as a result of natural selection pressures in either an animal host, or in humans themselves through adaptive mechanisms, allowing them to bind more effectively to human cells.
Based on the strong similarities of COVID-19 to related human and animal coronaviruses, it is clear from the study that the virus was not generated in a lab and has a natural origin. Moreover, artificial engineering of a virus requires a DNA backbone or template, which is often derived from an animal such as the mouse. In fact in 2013, a research group generated a new coronavirus that was “a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone.” The study by Andersen and colleagues, however, shows no evidence of genomic components related to mouse or any other animal (unrelated to the bat or pangolin) in the genome of COVID-19, further debunking the claim that it is a laboratory-made virus.
“Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus,” states the study.
The Huanan market in Wuhan, China is where many of the early cases of COVID-19 were traced back to and is where possible animal hosts such as the bat and pangolin, many of which were illegally imported into the city, were present in confined spaces, housing the perfect breeding grounds for viral transmission.
In the study, analysis of pangolin coronaviruses showed a high degree of similarity to COVID-19, with all six spike RBD amino acids actually being the same between the two. This suggests that the RBD of COVID-19 was modified to enhance human cell binding through natural selection that occurred in the pangolin, which may have served as a secondary host for a bat coronavirus. Interestingly, neither bat nor pangolin coronaviruses contain the spike cleavage site, suggesting further selection changes may have occurred during human-human transmission.
The findings of the study effectively dispel the myth that COVID-19 is a lab-generated virus as its origins can be traced back to naturally-occurring, known coronaviruses. While the exact evolutionary path of COVID-19 remains unclear, examining mutational changes associated with specific natural selection pressures during zoonotic or human-human transmission can help elucidate its trajectory.