The new SARS-CoV-2 line has spread across many Brazilian states

Researchers in Brazil have identified a new line of acute respiratory coronavirus 2 (SARS-CoV-2) syndrome in Brazil that has spread across several states in the country.

The SARS-CoV-2 virus is the agent responsible for coronavirus disease 2019 (COVID-19) which remains a threat to global public health and the global economy.

Marilda Siqueira of the Oswaldo Cruz Institute (Fiocruz) in Rio de Janeiro and colleagues say that this new interest variety (VOI) appears to have emerged in August 2020 and is already widely distributed. in Brazil.

Named as N.9, the variant appeared in line B.1.1.33 and accounted for 35% of all B.1.1.33 sequences detected between November 2020 and February 2021.

The VOI N.9 harbors E484K mutations in a surface structure called the spike protein, which the virus uses to bind to and infect host cells.

E484K mutation in a spike (S: E484K) is considered to be one of the most critical mutations as it may contribute to immune deficiency. Studies have shown that it resists some monoclonal antibodies and reduces the sera neutralization strength of individuals and vaccines.

The researchers predict that in 2021 the COVID-19 epidemic in Brazil will be controlled by a complex set of 484K variants that will completely replace the 484E parent strains the disease cleared during 2020.

The team advises that effective mitigation measures will be critical to reduce community outbreaks across Brazil and prevent more widespread changes that could exacerbate epilepsy.

A pre-printed version of the research paper can be found on the bioRxiv* server while the article is under peer review.

Study: A variety of SARS-CoV-2 potential inhibiting E484K mutation in the Spike protein was identified within the B.1.1.33 line circulating in Brazil.  Image credit: Pong Ch / Shutterstock

More about the disease in Brazil

The SARS-CoV-2 epidemic in Brazil was largely driven by the B.1.1.28 and B.1.1.33 lines that came out in February 2020 before becoming major changes in most regions by October 2020.

Since then, genomic studies have shown that two rapidly spreading variants (P.1 and P.2) have emerged within the B.1.1.28 line that harbor mutations in the protein receptor binding domain. spike.

Lineage P.1, first described in January 2020, is considered a variable perturbation (VOC), as it harbors an unusually high number of spike mutations (including K417T, E484K , N501Y) and was associated with a second wave of epidemics in the state of Amazonas.

The P.2 line, first described in October 2020, just ports E484K in the spike and four mutations that are outside the spike. This line, estimated to be the difference in interest (VOI) was the most common variance found in several states in late 2020 and early 2021.

There were also several changes in line B.1.1.33, including line N.1 found in the USA, N.2 found in Suriname and France, N.3 circulation in Argentina, and lines N.4 and B.1.1. 314 circulating in Chile. However, none of the mutations identified in these new sequences did cause damage to mutations in the spike protein.

a) Most probable phylogenetic tree (ML) of the whole-genome B.1.1.33 strains from Brazil.  The B.1.1.33 sequences with mutation S: E484K are represented by pink (VOI N.9) and green [B.1.1.33(E484K)] circles.  VOI cover N.9 is highlighted in pink.  ALRT support values ​​are denoted in key nodes and finger lengths are drawn to scale with the left bar indicating the nucleotide subunits of each site.  b) Geographical distribution of the VOI N.9 identified in Brazil.  Names of Brazilian states follow ISO 3166-2 standard.  c) Correlation between sampling date of B.1.1.33 sequences and their genetic distance from ML phylogenetic tree root.  Colors mark the cover of B.1.1.33 as shown in a).  d) Bayesian phylogeographic analysis on line N.9.  The colors of tips and branches indicate the sampling state and the most likely found location of their descendant nodes, respectively, as seen in the legend.  Branch posterior probabilities are indicated in major nodes.  Boxes illuminating two N.9 subfolders carry additional mutations (marked in each box).  The tree was automatically rooted under the assumption of a hard molecular clock, and all lengths are horizontal according to a time scale.

a) Most probable phylogenetic tree (ML) of the whole-genome B.1.1.33 strains from Brazil. The B.1.1.33 sequences with mutation S: E484K are represented by pink (VOI N.9) and green [B.1.1.33(E484K)] circles. VOI cover N.9 is highlighted in pink. ALRT support values ​​are denoted in key nodes and finger lengths are drawn to scale with the left bar indicating the nucleotide subunits of each site. b) Geographical distribution of the VOI N.9 identified in Brazil. Names of Brazilian states follow ISO 3166-2 standard. c) Correlation between sampling date of B.1.1.33 sequences and their genetic distance from ML phylogenetic tree root. Colors mark the cover of B.1.1.33 as shown in a). d) Bayesian phylogeographic analysis on line N.9. The colors of tips and branches indicate the sampling state and the most likely found location of their descendant nodes, respectively, as shown in the legend. Branch posterior probabilities are indicated in major nodes. Boxes illuminating two N.9 subfolders carry additional mutations (marked in each box). The tree was automatically rooted under the assumption of a hard molecular clock, and each length is horizontal according to a time scale.

What did the current study cover?

Siqueira and colleagues performed genomic analysis of SARS-CoV-2-positive samples in sequence with the Fiocruz COVID-19 Genomic Analysis Network between 12th March 2020 and 27th January 2021.

They identified 422 sequences within the B.1.1.33 line that were then combined with B.1.1.33 Brazilian genomes available in the EpiCoV GISAID database with 1st March 2021.

A mutational profile showed that S: E484K mutation was present in 34 of the B.1.1.33 sequences.

Phylogenetic analysis of the new VOI sequences identified what could be identified as the N.9 line containing S: E484K mutations and detected in various states across Brazil between November 2020 and February 2021.

The VOI N.9 has been found in ten Brazilian states, suggesting that this line has already spread across the country.

The variant was first discovered in Sao Paulo on the 11thth November, 2020, and then marked later in the Southern (Santa Catarina), North (Amazonas and Para) and Northeast (Bahia, Maranhao, Paraiba, Pernambuco, Piaui, and Sergipe) regions.

“Major global shift in the SARS-CoV-2 fitness environment”

Further analysis suggested that the N.9 line may have appeared in Sao Paulo, Bahia or Maranhao around 15th of August 2020.

“The start date of the N.O VOI here calculated around mid-August is roughly parallel to the estimated time that the P.2 VOI appeared at the end of July and ‘shortly before a major global shift in the SARS-CoV- 2 fitness landscape is discovered after October 2020,’ the researchers wrote.

The team says the VOI N.9 is already widely distributed in the country and makes up 35% of the B.1.1.33 series detected between November 2020 and February 2021.

Siqueira and colleagues say that the S: E484K mutation has appeared independently in various VOCs and VOIs that are rapidly spreading around the world.

“It may be an example of convergent evolution and the ongoing transformation of the virus to the human host,” they write.

Effective mitigation measures will be “essential”

The researchers say they expect epilepsy in Brazil in 2021 to be controlled by a complex series of B.1.1.28 (484K) and B.1.1.33 (484K) changes. which will completely replace the 484E series of parents who passed the epilepsy. in 2020.

“The implementation of effective mitigation measures in Brazil is crucial to reduce community outbreaks and to prevent the recurrence of more widespread changes that could exacerbate epilepsy in the country,” the team concluded. .

* Important message

bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.

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