The delta variant is gaining ground across the globe. The delta variant is the most transmissible
strain of coronavirus and it has the ability to evade antibodies against the original strain.
The delta variant is causing spikes in new cases even in nations with high vaccination
rates. Delta has become the dominant strain in the UK representing 95% of new cases. The
Delta variant now accounts for greater than 50 percent of new infections in parts of the
United States particularly among unvaccinated groups. The delta variant is sweeping across
Europe, Africa, Asia, the middle east and Australia.
Delta is one of several strains that have been designated by public health agencies
as variants of concern. These are the B.1.1.7 first found in the UK. B.1.351 first
identified in South Africa. P.1 found in Brazil. And B.1.617.2 first isolated in India.
The World Health Organization has recommended naming these strains with Greek letters to
simplify the nomenclature and to avoid attribution to any country or region.
As long as the coronavirus replicates, mutations are inevitable. Mutations, that is changes
in the amino acid sequence, occur randomly. After the virus binds to the ACE2 receptor
via the spike protein, the virus s RNA infiltrates the host cell. The viral enzyme RNA dependent
RNA polymerase makes multiple copies of the virus s RNA. It is prone to making replication
errors. (pause) The viral RNA copies are then translated to viral protein leading to more
virus particles which then go on to infect other cells. The vast majority of the changes
are neutral or deleterious to the survival of the virus, but very rarely, after billions
of replication cycles, the virus hits the winning combination and finds an amino acid
change, or several changes, that confer better survivability. These strains proliferate and
become dominant. This is a consequence of natural selection. The new strains evade the
host immune system, are transmitted between people more easily and enter cells more easily.
The spike protein, which protrudes from the surface of the virus particle, is considered
the most important component for infectivity because it binds to the ACE2 receptor. Also,
the spike protein elicits the greatest number of antibodies to the SARS CoV-2 virus. Like
all proteins the spike is folded up as a knotted three-dimensional shape. If we spread the
protein apart, we see that there are ten mutations (or alterations) in the delta variant.
Each mutation is shown using the amino acid code and the amino acid sequence number. For
example, in this mutation, Threonine (T) is replaced by Lysine (K) at the 478th amino
acid residue in the spike protein. Residues 156 and 157 have been deleted. The mutations
can lead to stronger interaction between the Spike protein and the host s ACE2 receptor.
While there may be antibodies against the original strain, the resistant variant has
acquired mutations in the spike protein which lead to weaker interactions between the spike
and antibodies, So called immune escape mechanisms. In people who had COVID disease, blood samples
showed lower neutralizing antibody activity against the Delta strain. So, if you were
infected before with coronavirus, you could be infected again with the Delta variant even
though you have antibodies against the original strain.
The L452R and the T478K mutations are in the receptor binding domain and are thought to
reduce antibody binding while enhancing binding to ACE2.
Changing the electrostatic potential of the receptor binding domain may improve binding
to the ACE2 receptor. The uncharged leucine at position 452 changed to the positively
charged arginine, and in position 478, the neutral threonine changed to the positively
charged lysine. These positively charged amino acid residues in the delta variant may increase
binding affinity to the negatively charged ACE2 receptor.
Other mutations have been found to improve the delta variant s fitness. (pause) The P681R
mutation in the furin cleavage site accelerates the cleavage of the spike protein, the first
step in viral fusion to the host cell. After more than 180 million cases of coronavirus
infections, and 4 million people dying from COVID-19, it seemed like the end was in sight.
If not for the delta variant, we might have been close to vanquishing this disease. Although
there have been cases of breakthrough infection among those who have been vaccinated, these
represent mild cases, not hospitalizations. The vaccines in the USA and Europe are effective
at reducing severe covid disease resulting from infection with the delta variant.
So, how can we stop new variants from popping up and spreading around the globe? That s
right! Get vaccinated. Only mass vaccination will prevent the appearance and spread of
coronavirus variants. As Angela Rasmussen has stated,
No infection means no replication No replication means no mutation
No mutation means no new variants
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