Novel Coronavirus variant is fast spreading in South Africa

Last week researchers in South Africa unveiled a viral variant of the Novel Coronavirus that is fast spreading.
The variant was discovered in routine genetic monitoring of novel Coronavirus in South Africa, appearing first along the coast and then spreading inland, and is currently named 501y.v2.

The variant is not the same as the B1.1.7 variant found in the UK earlier this month.
However, after comparing the genome sequences of the two viral variants, South African scientists found that they both contained mutations of N501Y in the receptor binding region of viral S protein (RBD), which can enhance the binding of the virus to the human receptor ACE2, thus accelerating the spread of the virus.

In October, just weeks after the peak of the first wave, South Africa had a second wave soon after.
By the end of October, the effective number of Re (the average number of infections per patient) had increased to more than 1, and the epidemic began to expand, with a steady increase in incidence.
In early December, the number of cases reached the first wave in the southern and eastern coastal provinces of South Africa (Eastern Cape, Western Cape and Kwazulu-Natal).

“Preliminary data show that the virus that dominated the second wave is spreading faster than the first.”
Said Professor Salim Abdool Karim, chair of the South African Government’s ministerial Advisory Committee.

The picture

Second wave in South Africa.
Figure Source: References [2]

1

What are the mutations of the South African mutant virus?

South African laboratory genetic monitoring Network (Network Genomic Surveillence) continue to will be coronavirus genetic sequence analysis and monitoring, has been in more than 50 locations of the country’s nearly 200 samples was found in this new mutation.

At the university of kwazulu-natal, institutions such as the researchers analyzed the solstice on March 5, 2020 in South Africa between November 25 upload 2589 whole genome sequence, draw the phylogenetic tree, on 15 October and November 25 kwazulu-natal, eastern cape and western cape provinces between 190 found a new genome sequence spectrum, namely 501 y. V2 variants.

The 501y. V2 variant first appeared in Nelson Mandela Bay in August and quickly spread.
Nelson Mandela Bay is a resort on the southeast coast of South Africa.

“When people come back from their coastal vacations, we can expect them to take this variant with them,” said Dr. Richard Lessells, who led the research on the new variant, which could also travel with tourists across borders to other African countries.

By early November, the 501y. V2 variant had become the dominant SARS-COV-2 virus lineage in South Africa.
As of December 17, 59 (88%) of the 67 genomes most recently uploaded belonged to that lineage.

The picture

501y. V2 has emerged as a major epidemic pedigree in South Africa.
Figure Source: References [2]

In addition to D614G, mutations (D80A, D215G, E484K, N501Y, and A701V) were observed at five sites of S protein in the first sample of this lineage on October 15.
By the end of November, there were three more mutations (L18F, R246I and K417N).

Among them, N501Y, E484K and K417N are on the key RBD, L18F, D80A and D215G are on the N-terminal domain (NTD), and A701V are on the folding ring. In addition, L242 site may also be missing or mutated, which has not been confirmed.

Among them, the proportion of most mutation sites in each genome is different, and the frequency is not stable over time, but the three mutations in RBD (N501Y, E484K and K417N) are present in almost all samples, and maintain high frequency at different times.

Researchers analyzed on December 24, 2019 and 2020 GISAID database between November 14, 142037 high quality genome sequence (5964 S) haploid type, think and N501 E484 two loci showed the nucleotide diversity of map may be associated with after the evolution of positive selection, the two sites are also present in the RBD interact with human receptor ACE2 interface functions.

2

What do these mutations mean?

The N501Y mutation is thought to accelerate the spread of the virus.
This mutation is also the main mutation from the novel coronavirusB1.1.7 pedigree, which is rapidly becoming popular in the UK.
N501Y can significantly enhance the binding affinity between S protein and ACE2, but there is no immune escape phenomenon, and there is no significant difference in the neutralization ability of Serum induced by N501 to Y501.

The picture

The STRAINS in the UK and South Africa are different.
20B/ 501y. V1 is a British endemic strain (light green), and 20C/ 501y. V2 is a South African endemic strain (orange).
Photo source: Nextstrain

Although E484K also provides evidence of a possible slight increase in ACE2 binding, it is of greater concern that there is a potential risk of immune escape.
A number of studies have shown that E484 is crucial to the immune dominant epitopes, and a single mutation can escape the neutralization effect of multiple monoclonal antibodies to varying degrees.
Researchers at the University of Washington have found that E484K has a certain degree of resistance to some monoclonal antibodies and serum of recovered patients, indicating that E484K has a relatively high probability of immune escape, but there are still a variety of monoclonal antibodies and serum that can neutralize the E484K strain.

The picture

E484K mutation has certain resistance to monoclonal antibodies and serum of rehabilitated patients.
Source: Adapted from references [7]

K417N has no significant effect on the binding affinity of ACE2, but for a class of specific antibodies (mainly encoded by VH3-53) targeting k417-centered antigen epitopes, K417N may affect the interaction with S protein, but there is no clear experimental evidence at present.
In fact, there is experimental evidence that if K417 mutates into another amino acid V417, it increases the sensitivity to some monoclonal antibodies.

Other mutation sites have not received much attention.
The A701V mutation was also reported frequently in the Malaysian strain, and more experimental evidence is needed to accurately describe these sites.
The researchers will also further study the characteristics of the 501y. V2 lineage, as well as continue to track a variety of other mutant strains.

At present, the available evidence does not prove that the virus variant in South Africa causes more severe illness, nor is there clear evidence that it is resistant to natural infection or vaccine-acquired immunity.
But epidemiologists worry that if the virus spreads quickly beyond the capacity of health care systems, it could cause an increase in deaths.

As of The evening of December 27 local time, the cumulative number of COVID-19 infections in South Africa has exceeded 1 million and the death toll has exceeded 26,000, making it the hardest-hit country in Africa.

The South African government will receive a vaccine to cover 10% of the population under the Covax Initiative, with the first vaccines expected to arrive in early 2021.
Now, South African officials are urging people to bring back face masks, pay attention to social distancing and wash their hands.

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