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NIH Article
All coronaviruses have a spiky crown composed of spike proteins. The spike protein is divided into two parts: S1 and S2. S1 is the binding component analogous to the biting of a door key, which inserts into the lock. It allows for the virus to attach to host cells which is a unique feature.
S2 acts as the key’s base, or bow, supporting S1 and facilitating the unlocking process.
The “keys” of the COVID-19 virus—specifically, its spike protein—can be inserted into the lock via ACE2 receptors in our bodies more easily and quickly than other close relatives. This contributes to its high transmissibility and widespread impact.
After the COVID-19 virus initially attaches to the ACE2 receptor, a “scissor” enzyme called FURIN in the human body cuts between the S1 and S2 of the spike protein. This cleavage allows the virus to bind to ACE2 more seamlessly. The S2 subunit then fuses with the human cell membrane, stabilizing the binding of the S1 subunit with ACE2.
Scissors function like keys with sawtooth patterns that fit perfectly into locks. Strikingly, the COVID-19 virus has precisely the required human scissor-cut point—12 additional nucleotides—in the location between the S1 and S2 subunits of its spike protein. This insertion is perfectly positioned for human enzymes to cleave the spike protein efficiently, which helps the virus enter human cells.
Among the betacoronavirus family, only the COVID-19 virus has the unique FURIN cleavage sequence.
“SARS-CoV-2 is the only one of more than 800 known SARS-related coronaviruses that possesses an FCS [FURIN cleavage site],” stated Richard H. Ebright, Board of Governors professor of chemistry and chemical biology at Rutgers University, during a June 18 congressional hearing.
“Mathematically, this finding—by itself—implies that the probability of encountering a natural SARS-related coronavirus possessing an FCS is less than one in 800,” he added.
Other unique genetic codes of the COVID-19 virus Unique Featureshave further reduced the odds of natural evolution.
“Based on these features,” the probability of it having naturally evolved from its natural ancestor virus is “less than one in 1.2 billion,” according to Dr. Steven Quay, a former faculty member at Stanford University School of Medicine, who testified at the hearing, supported by his analytical report.
This number is roughly calculated based on the phylogenetic tree theory. Even the genes of its closest relative virus, RaTG13—claimed to be the ancestor of COVID-19 by virologists from Wuhan—are only 96 percent identical to the COVID-19 virus, with more than 1,000 nucleotide differences.
According to molecular clock theory, it would take a long time—potentially several hundred thousand years—for the virus RaTG13 to naturally evolve into COVID-19, and there is no evidence to support such a lengthy evolutionary period. Consequently, scientists do not convincingly regard RaTG13 as the ancestor virus of COVID-19.
Simply put, based on current scientific theories, virologists cannot identify a reasonable ancestor virus for the COVID-19 virus. Nevertheless, there is some debate over these calculations, and not all experts rule out natural evolution.
Meanwhile, the Wuhan Institute of Virology (WIV) was located in the same city where the COVID-19 pandemic originated. WIV has a long history of researching bat-related coronaviruses and SARS-like viruses. The institute has also done significant gain-of-function (GOF) research, which involves enhancing a virus’s functions. The WIV naturally drew the world’s attention and became the focal point of the origin debate for the COVID-19 pandemic.
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