Breaking News! Brazilian Variant Of Concern-The Gamma Or P.1 Variant Has Further Evolved With A New Mutation And Deletion Found In More Potent Second Generation Variants!

More good news! The variant of Concern found in Brazil called the P.1 Strain or The gamma Strain has further evolved with its second generation variants now spotting a new mutation and also a deletion on its genome. These new mutations and deletions are making the newly emerging second generation variants even more transmissible and also evasive to the immune system.

Alarmingly, these second generation variants of the Gamma lineage are gaining a fast foothold in Brazil, accounting for almost 78% of all new SARS-CoV-2 infections in the country! It is reported that those that were initially infected are getting re-infected again with the new variants and often with more serious symptoms and outcomes.
 
Virologist and scientists from Brazil report that the two types of additional changes in the Spike protein are deletions in the N-terminal (NTD) domain (particularly 141-144) and mutations at the S1/S2 junction (N679K or P681H).
 
The study findings of these new emerging Gamma lineage variants were published in official website: Virological.org
https://virological.org/t/emergence-and-spread-of-sars-cov-2-p-1-gamma-lineage-variants-carrying-spike-mutations-141-144-n679k-or-p681h-during-persistent-viral-circulation-in-amazonas-brazil/722

According to the study team, the Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic, and by 15th June 2021, 13,162 deaths had been reported. The COVID-19 epidemic in Amazonas was characterized by two waves of exponential growth. The first one started in March 2020 and peaked around early May 2020, and was primarily associated with the introduction and dissemination of lineages B.1.195 and B.1.1.28. The second one started in December 2020 and peaked around early February 2021 and was associated with the local emergence and rapid spread of a new SARS-CoV-2 Variant of Concern (VOC), firstly detected in Japanese travelers returning from the Amazonas State, Brazil, designated as lineage P.1 or Gamma. Since mid-February 2021, the number of SARS-CoV-2 deaths dropped and remained roughly stable (7-day average <20) from May to June 2021.
 
Strangely however despite both the number of infected people in the two waves of the COVID-19 pandemic and the percentage (37.1%) of fully vaccinated individuals supports a high prevalence of individuals with anti-SARS-CoV-2 antibodies in the Amazonas state, the virus continues to circulate and an average of 518 new SARS-CoV-2 positive cases per day were diagnosed during 1st May and 15th June 2021.
 
The study team hypothesized that continuous transmission of the VOC Gamma in the Amazonian population with high levels of immunity acquired from both natural SARS-CoV-2 infection or vaccination might select for second-generation of P.1 variants that are more resistant to neutralization than the parental virus.
 
In order to test this hypothesis,the team generated 744 SARS-CoV-2 high-quality, whole-genome sequences from individuals living in the Amazonas state from 01st January to 31st May 2021. Viral sequences were generated at FIOCRUZ Amazônia, which is part of both the Amazonas state health genomics network (REGESAM) and the consortium FIOCRUZ COVID-19 Genomics Surveillance Network of the Brazilian Ministry of Health.  ( ref="https://www.genomahcov.fiocruz.br/">https://www.genomahcov.fiocruz.br/).
 
The genomic survey confirms that P.1 was the most prevalent lineage representing 99% (744 of 752 genomes) of all samples analyzed in the Amazonas state across the study period.
 
Alarmingly however the study results also revealed a sharp increase in the prevalence of P.1 variants harboring two types of additional changes in the Spike (S) protein: deletions in the N-terminal (NTD) domain (NTDdel) or mutations at the S1/S2 junction (N679K or P681H).
 
The P.1+NTDdel variants increased from <10% in January-April to 16% in May 2021. NTDdel at the N3 loop (144, 141-144, and 138-143) were much more frequent than that at N5 loop (241-243 deletion), and the P.1+141-144 variant displayed the most significant increase in prevalence during May 2021. The P.1+P681H and P.1+N679K variants increased from 0% in the first half of March to 29% and 32% in the second half of May 2021, respectively. Together, the P.1+NTDdel, P.1+P681H, and P.1+N679K variants resemble 78% of all SARS-CoV-2 positive cases that underwent genomic sequencing in Amazonas in the second half of May 2021.
 
The VOC Gamma is already sensitive to neutralizing antibodies (NAb) directed against the NTD antigenic supersite and NTD deletions mapping in the recurrent deletion region-2 (RDR-2), such as the 141-144, has been shown to confer resistance to those antibodies.

Studies of intra-host SARS-CoV-2 evolution revealed that NTD deletion 141-144 emerged following therapy with convalescent plasma in immuno-compromised hosts, during persistent SARS-CoV-2 infection in individuals with partial humoral immunity and following the development of autologous anti-NTD antibodies during acute infection in one immunocompetent individual.
 
Interestingly, NTD deletions 141 and 142 were among the selected forecasted mutations that may contribute to SARS-CoV-2 VOCs shortly, according to a recent study.
 
These study findings support that P.1 variants bearing NTD deletions detected in the Amazonas and other Brazilian states might represent a primary mechanism of further immune evasion of the VOC P.1.
 
The mutations S:P681H/R have emerged in the VOCs Alpha and Delta as well as in several VOIs (AV.1, B.1.1.318, B.1.617.1, B.1.617.3, and P.3), and reached a worldwide prevalence >70% among SARS-CoV-2 sequences sampled in May 2021. (outbreak.info).
 
Mutations S:P681H/R are immediately adjacent to the S1/S2 furin cleavage site (681-P-R-R-A-R|S-686), which is a region of importance for SARS-CoV-2 transmission, and both provide an additional basic residue adjacent to the cleavage site that may modulate S1/S2 cleavability by furin. Indeed, functional studies confirm that mutation S:P681R facilitates the furin-mediated spike cleavage and enhances viral infectivity and the efficacy of viral fusion and cell-cell viral spread, particularly when it occurs in the background of other S changes. Furthermore, P681R-harboring pseudoviruses were partially resistant to anti-RBD NAbs, suggesting that mutations at this position may also conformationally mask epitopes located in the RBD, blocking the accessibility of NAb to that domain.
 
Mutation S: N679K has not been previously identified as a mutation of concern. As of 25th June 2021, the EpiCoV database contains 2,585 sequences with that mutation associated with multiple SARS-CoV-2 lineages found predominantly in Europe (n =1,298) and North America (n = 1,129). The first appearance of this mutation occurred in the USA on 18th March 2020, but 97% of SARS-CoV-2 sequences with mutation S:N679K were detected from November 2020 onwards. In Europe, mutation S:N679K is found together with mutations of concern in the S protein of SARS-CoV-2 lineages B.1.1.433 (S477R), AT.1 (136-144, E484K and ins679GIAL) and B.1.258 (69-70 and N439K) and was also sporadically detected in a few B.1.1.7 (n = 30) and P.1 (n = 19) genomes.
 
The position of mutation S:N679K close to the furin cleavage site, the change for an additional basic residue, and its recurrent emergence on backgrounds with mutations of concern in the S protein is striking and warrants additional studies to analyze its potential functional consequences of this mutation.
 
The furin enzyme cleavage site is composed of negatively charged residues (ASP154, ASP191, GLU236, ASP264, ASP306) that contact the substrate, forming a pocket with a remarkable negative electrostatic surface.
 
The furin cleavage site on protein S is composed of positively charged residues so that there is a complementarity not only in shape, but also in charge between the enzyme and the substrate. Mutations N679K and P681H exchange neutral residues for two positively charged residues adjacent to the cleavage sites. The study team hypothesizes that the positive charge increase will benefit enzyme-substrate coupling.
 
The study findings confirms that the persistent circulation of SARS-CoV-2 after the second COVID-19 epidemic wave in the Amazonas state has been associated with the continuous evolution of the VOC P.1 through the acquisition of either Spike NTD deletions or mutations at the S1/S2 junction (N679K or P681H). The rapid spread of emergent variants P.1+141-144AM, P.1+N679KAM, P.1+P681HAM, and P.1+P681HBR during May 2021 suggests that those P.1 sub-lineages are likely to continue to spread over the coming months in Amazonas and other Brazilian states.
 
Although the emergence of these new viral variants was not associated with a third COVID-19 epidemic wave in the Amazonas state until now, the community transmission of second-generation VOCs that could be more transmissible or resistant to neutralization than the parental one should be carefully monitored.
 
The study findings also highlight the urgent need to address the efficacy of sera from P.1-infected and vaccinated individuals to neutralize these new emergent SARS-CoV-2 P.1 sub-lineages.
 
Thailand Medical News would also like to add that despite the advent of COVID-19 vaccines and ignorant virologist claiming that the virus will evolve to become weaker or that COVID-19 will become an ordinary endemic phenomena like the flu, the world is in for a rude shock. First SARS-CoV-2 is not going away anytime soon even with vaccines or so called herd immunity projections. Rather the COVID-19 pandemic is  expected to last for at least another 6 years or more unless a proper combination of antivirals and therapeutics is identified or developed. A single therapeutic agent will only result in drug resistant strains developing. Also the surges will continue, each time with the advent of one or more potent variants emerging and becoming dominant in circulation and every new surge will result in a greater amount of infections and deaths than the previous. The pandemic will no longer also be a single pathogen that we are dealing with, rather every emerging variant is causing a new pandemic by itself and also we will be faced with a a major global health crisis arising from long COVID where the actual long term health and medical conditions will start to become more apparent including not just neurodegenerative diseases but also a variety of cardiovascular, gastrointestinal and oncological manifestations. Existing medical textbooks and protocols will no longer be valid. It is really going to be fun times ahead. Lets hope however that nasty countries like the United States, the United Kingdom, China, India, And Singapore (India and Singapore is where many of these American tech companies have their regional offices  and where many of their locals are worshipping these filthy white garbage owners!)  and nasty people  like those from the giant pharmaceutical companies, politicians and the American tech companies and social media platforms and American mainstream media that have been trying to control the COVID-19 narratives will be worst affected!
 
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