High rates of mutation accumulation over short time periods have been reported previously in studies of immunodeficient or immunosuppressed patients who are chronically infected with SARS-CoV-2. The patients are treated with convalescent plasma and usually also with the drug remdesivir. Virus genome sequencing of these infections reveals unusually large numbers of nucleotide changes and deletion mutations and often high ratios of non-synonymous to synonymous changes.
A terrible mutant strain of the SARS-CoV-2, B.1.1.7, was discovered in the UK. This new strain has 23 special mutations. This new strain has a mutation of N501Y in the six key interface amino acids of RBD, and a mutation of P681H occurred in the position adjacent to the Furin cutting site. The Furin protease cleavage site has a huge impact on the ability of SARS-CoV-2 to bind to host cells. The stability of the S protein after Furin cleavage is reduced, thus exposing the open domain, thereby increasing the binding affinity of the S protein to the human ACE2 receptor by 1000 times.
In addition to the obvious increase in the spread of the new strain, there are other dangers waiting to be verified.
Table 1. Non-synonymous mutations and deletions inferred to occur on the branch leading to lineage B.1.1.7 lineage.
gene | nucleotide | amino acid |
ORF1ab | C3267T | T1001I |
C5388A | A1708D | |
T6954C | I2230T | |
11288-11296 deletion | SGF 3675-3677 deletion | |
spike | 21765-21770 deletion | HV 69-70 deletion |
21991-21993 deletion | Y144 deletion | |
A23063T | N501Y | |
C23271A | A570D | |
C23604A | P681H | |
C23709T | T716I | |
T24506G | S982A | |
G24914C | D1118H | |
Orf8 | C27972T | Q27stop |
G28048T | R52I | |
A28111G | Y73C | |
N | 28280 GAT->CTA | D3L |
C28977T | S235F |
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