Variant of Concern 202012/01 (VOC-202012/01)
By: Nana Dadzie Ghansah
Tags: Mutation, Covid-19, Vaccines, Health, Variant

By Nana Dadzie Ghansah

From the NYTimes

The Variant of Concern 202012/01 (VOC-202012/01), also known as Variant Under Investigation in December 2020 (VUI — 202012/01), and Lineage B.1.1.7 is a variant of SARS-CoV-2 that was first detected in Kent County of the UK in September 2020.

In November, public health officials in the UK were stumped as to why cases in Kent county were increasing despite national restrictions. Through genomic studies, they found the new variant to cause a much faster spread of COVID-19.

How did this variant come about?

Through 23 mutations. Seventeen (17) of these mutations led to changes in viral proteins, while six did not. The mutations are in the spike protein (S), the nucleocapsid (N), and two other proteins — ORF1ab and ORF8.

Are these mutations concerning?

Viruses mutate to escape the effect of antivirals, the immune system and adapt to their environments. Although over 4000 mutations in the SARS-CoV-2 genome have been found, these new ones are noteworthy. There are eight of them alone in S, of which three are concerning.

The first and most concerning mutation is called N501Y.

This mutation came about because, at position 23,063 of the viral genome, the nucleotide Adenosine was replaced by Thymine. This led to a change in amino acids at position 501 in the spike protein. Instead of Asparagine (N), this variant has Tyrosine (Y). Hence N501Y.

The amino acid at position 501 plays a crucial role in how the virus binds to the human ACE receptor. This mutation makes the virus bind even better.

In a study by Gu et al., the N501Y mutation was induced in a mouse by passing the virus several times through the rodent. The variant was found to be more virulent. (Science 369 (6511): 1603–7).

The second concerning mutation is called P681H.

This one came about because, at position 23,604 of the viral genome, Cytosine was replaced by Adenosine. This led to a change in amino acids at position 681 of the spike protein. Histidine replaced Proline — P681H.

This amino acid is adjacent to the site where the enzyme Furin cleaves S1 of the spike protein from S2 and allows S2 to fuse the virus with the human cell. Like the N501Y mutation, P681H could also make this variant more transmissible.

The third concerning mutation is actually a deletion.

Six nucleotides are lost from positions 21765 to 21770. This led to two amino acids — Histidine and Valine — getting deleted altogether from positions 69 and 70.

This mutation has been seen in reports about three immunocompromised patients who were resistant to antibody treatment with convalescent plasma and Remdesivir. They continued to shed the active virus for weeks. Also, it makes certain diagnostic tests unable to detect the spike protein (S) gene.

So in all, the worry is that these mutations make the virus more transmissible. A model created by Davies N et al. postulates a 70% increase in transmissibility. The other concerns are that this variant may cause more severe disease, escape the effect of the antibody cocktails and vaccines we have available now.

What may have led to these mutations?

In three case reports, it was shown that there was an inability to mount an adequate immune reaction to the virus in these immunocompromised patients. This led to these patients harboring and shedding active virus for a long time and allowing it to change. Genomic studies on the virus in these patients showed many changes compared to patients who were not immunosuppressed.

The authors of these reports also noted that giving these patients convalescent plasma may have added to the pressure on the virus to adapt and escape the effects of the exogenous antibodies in these immunocompromised patients. Moreover, the antibodies in the convalescent plasma could have selected for the virus that had gained a mutation or mutations that made it resistant to the antibodies in the plasma. (Choi et al. 2020, in NEJM; Avanzato et al. 2020 in Cell; Kemp et al. 2020 on MedRxiv)

What about the variant that was found in South African?

That variant is called 501.v2. It was found earlier this month and is prevalent among otherwise healthy young adults, and is resulting in serious illness.

Besides the N501Y mutations, it also has two more mutations in the spike protein, S — K417N and E484K. These mutations are near the receptor-binding domain (RBD) of the spike and may make it more transmissible.

Nigeria also announced a new variant but has not published any information on it so far.

Are the vaccines still effective against this variant?

That is the million-dollar question.

In a statement, Moderna points out that the spike protein has 1273 amino acids. In the new variant, eight are affected. That is less than 1% of the amino acid coded for in the vaccine, mRNA-1273. Based on their data, they believe the vaccine will be effective against B.1.1.17.

The folks at Pfizer-BioNTech expressed a similar sentiment. The CEO of BioNTech stated that they could produce a vaccine that encompassed these mutations in weeks.

Both companies’ vaccines cause the body to make antibodies to the numerous epitopes on the spike protein. The hope is that these few mutations will not make the virus resistant to the vaccines.

Experiments are running, and only time will give us the right answers.

Until then, get a COVID-19 vaccine if you are eligible, wear a mask, social distance, and avoid crowds and closed spaces with bad ventilation.

Stay safe.