Question

**The following scenario is fictitious and not based on real events**

Assume that patients with COVID19 develop antibodies identical to m396 after infection. Initially, these patients benefit from the neutralizing activity of that antibody. However, after 3 days several patients show a recurrence of viral proliferation, which is accompanied by the emergence of a mutated version of the virus, COVID19.2. Sequencing identifies only a single amino acid mutation in the spike protein of COVID19.2, Y491F:

                     480        490       500        510        520

                     |          |          |          |          |

SARS1       ALNCYWPLND YGFYTTTGIG YQPYRVVVLS FELLNAPATV CGPKLSTDLI

COVID19     GFNCYFPLQS YGFQPTNGVG YQPYRVVVLS FELLHAPATV CGPKKSTNLV

COVID19.2   GFNCYFPLQS YGFQPTNGVG FQPYRVVVLS FELLHAPATV CGPKKSTNLV

Amino acids highlighted yellow correspond to those shown in the figure above.

Some patients show a R58W antibody mutation that confers better recovery outcomes. What antibody-antigen interaction(s) might have achieved this?

b. You suspect that enzyme-mediated DNA modification in immune cells is responsible for the R58W antibody mutation. What is the name for this process?

c. Assuming only one nucleic acid was changed to achieve this mutation, what codon was mutated?

Original:

Mutated:

Draw the enzyme reaction that caused this mutation:

d. What is the percent identity between these sequences?

SARS1 and COVID19, residues 471 - 520:

SARS1 and COVID19, residues 486 - 492:

Answer 1

Answer a:)

Antibodies IgM, IgA, IgG are responsible for antiviral activity. The m396 infection used a reaction with the IgG antibody. R58W antibody mutation is associated with CD27 expression in T cells. Therefore, there would be antigen-specific T cell activation. This is MHC class II immunity caused by antigen-presenting cells.

Answer b:)

This process is called histone methylation/demethylation or histone acetylation/deacetylation in which DNA is opened or restricted to perform a particular task.

Answer c:) Original

Arginine is coded by CGG in one of four other codons CGG/CGT/CGC/CGA while to convert into tryptophan (W) there is only C replace by T. Therefore, the codon originally can be mutated.

Answer d:)

Residues 471 – 520:

ALNCYWPLND YGFYTTTGIG YQPYRVVVLS FELLNAPATV CGPKLSTDLI

GFNCYFPLQS YGFQPTNGVG YQPYRVVVLS FELLHAPATV CGPKKSTNLV

There are 13 different amino acids in total 50 amino acids in between SARS1 and COVID19. Therefore, the percent identity = (50 – 13) /50 x 100

The percent identity = 37 x 2

The percent identity = 74%

Residues 486 - 492:

100% identity due to the same amino acids.

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