In the early days of the coronavirus pandemic, the Philippine Genome Center (PGC) sequenced SARS-CoV-2 as part of their study for locally developed RT-PCR test kits. They acquired COVID-19 positive samples from the Philippine General Hospital collected last March.13 of these samples showed the strain D614 — the original genotype found in the outbreak from Wuhan, China.
The Research Institute of Tropical Medicine (RITM) also found the same strain in the samples they collected and tested. All in all, the Philippines had 20 samples that showed the same strain. Both the RITM and PGC eventually deposited these to the database of the Global Initiative on Sharing All Influenza Data (GISAID), a worldwide project that allows open-access to virus-related scientific information.
But at this time, samples from all over the world are starting to show a divided trend. While some show the original D614 genotype, a new strain of the coronavirus was spreading: the G614, which first appeared in China and Europe around January, and eventually found its way to the United States in March.
As of July, around 75% of the 50,000 samples in GISAID’s database carry the mutation called “D614G,” showing the indisputable dominance of the G614 strain.
The Science Behind the Mutation
In the most basic terms, a virus is a genetic material (RNA in the case of the coronavirus) wrapped in a protein shell. On its core are amino acids that serve as building blocks of its membrane, nucleocapsid, envelope, and (the infamous) spike proteins.
These spikes alone are composed of about 1,300 amino acids. Like a key to a lock, the virus uses these spikes as a tool to latch itself and enter human respiratory cells resulting in an infection that can spread through large droplets like spit or mucus, or through smaller ones that hang in the air when you speak or sneeze. They may also end up on surfaces, turning them to fomites. If a person touches this fomite and then touches their face, they may also end up getting infected.
While infections happen from one host cell to another, the virus can make copies of itself by co-opting the existing biological machinery of human cells. That is one of its primary goals. And the reason why we use the word copy and not duplicate is that, during this process, there are chances wherein the copies are not exactly the same. Changes like this naturally occur as the virus evolves, and, most of the time, they do not have a significant effect on the behavior of the virus — whether on its virulence or severity. This is how mutations occur.
The letter-number combination of the strain that spread the virus is also significant. The letter pertains to the amino acid (D stands for aspartic acid; G for glycine), while the number points to the placement of the amino acid in the thousands of building blocks that make up the virus. In the case of the D614G mutation, the change happened in the 614th amino acid where the D switched to a G. Coincidentally, the number 614 amino acid is part of the amino acids that comprise its spike proteins.
According to studies from Scripps Research, a US-based institute, the change from aspartic acid to glycine gave the G614 strain more spike proteins that are stronger than the ones on its ancestral strain. This makes the virus “approximately ten times more infectious in the lab experiment.”
But this is precisely why the news about the mutation shouldn’t be a cause for alarm.
In a paper on Cell, a prestigious scientific journal, researchers said that, although it seems like the G614 strain is more transmissible as observed on lab experiments, there is not enough evidence that the same can be said when observed on mixed human populations.
The researchers also said that, in their observations, hospitalization outcomes showed no significant difference despite the presence of the G614 variant. The same is true for the cases found in the United Kingdom and the United States.
PGC echoes this in their briefer. “Together with the observation that G614 is now the dominant viral state, the authors claim that the said mutation can increase the viral rate of transmission. However, there is still no definitive evidence showing that carriers of the G614 variant are more transmissible than those with D614, and the mutation does not appear to substantially affect clinical outcomes as well.”
This means that, although laboratory experiments using culture cells show that the mutation can potentially affect the infection rate of the virus, a definite conclusion cannot be drawn just yet. After all, there have been instances in the past wherein experiments with cells on a petri dish did not yield the same results when done on clinical trials with humans.
It is also highly unlikely that the mutation can affect the ongoing development projects of antibody-mediated vaccines and treatments. However, as PGC pointed out, monitoring mutations, such as the D614G, must be prioritized to see how the virus evolves. Knowledge about mutations can help the government and experts to make informed decisions pertaining to the control of contagion, diagnostics, and therapeutic strategies.
You may read the Cell paper here: https://www.sciencedirect.com/science/article/pii/S0092867420308175