NewsBeezer (Brasil em inglês)

Scientists describe possible mechanisms that enable the South African variant of the coronavirus to escape the immune system

Publicado em 20 abril 2021

A group of researchers from the Medical School of the University of São Paulo (FMUSP) believe they have found the mechanism that allows the South African variant of Sars-CoV-2 (also known as B.1.351) to escape the antibodies it generates previous infections by the strain of the virus.

The discovery, which has yet to be confirmed by new experiments, could pave the way for the development of effective vaccines against the variant that has already appeared in South Africa and that already exists in Brazil and against the one from Manaus (P.1). as well as their predecessors.

The study, which was published as a form on the medRxiv platform, is in the peer review process.

Using computer simulations, the group studied the key protein of Sars-CoV-2, known as spike. It is responsible for binding to the receptor of human cells (the ECA2 protein) and enabling infection.

The results suggest that one of the mutations at the top of the tip of the South African variant – characterized by the replacement of the amino acid lysine for asparagine – may lead to the appearance of a biochemical phenomenon known as glycosylation, which changes the trait of the viral protein and prevents the binding of antibodies. In the P.1 variant, lysine is replaced by a threonine that does not undergo glycosylation.

“Today, when developing a vaccine, one has to choose what is most effective against the virus, including the variants. In the case of Sars-CoV-2, two of the three mutations that occur in P.1 and B.1.351 are exactly the same. It is therefore possible that a vaccine that focuses on the South African variant will also be effective against P.1 and against the ancestral virus. However, vaccines against the latter two are likely to be less effective against the South African variant, ”explains Keity Souza Santos, professor at FMUSP and author of the article.

The work is the result of a project supported by Fapesp and coordinated by Jorge Kalil, professor at FMUSP and coordinator of the Immunology Laboratory at Instituto do Coração (InCor), which also signs the article.

The group led by Kalil is working on the development of a vaccine against Covid-19. The project is supported by the foundation and the Financier of Studies and Projects (Finep).

“Previous work by other groups has failed to find the specific region where human antibodies bind to RBD [domínio de ligação ao receptor, na sigla em inglês]is known as the tip of the spike protein that fits human cells. By then, conclusions had been drawn. We used a technique that allowed us to pinpoint a predominantly recognized region that we call immunodominant. It’s the same thing that one of the mutations occurs in the Manaus and South Africa variants, ”says Santos.

After identifying the region in the first strain of the virus, the group of researchers from the USP, Universidade Estadual Paulista (Unesp), the Federal University of São Paulo (Unifesp), and the University of Salzburg (Austria) submitted the amino acid sequence to which the blood serum of 71 patients was initially recovered from Covid-19 during the pandemic in Brazil in the hospital das Clínicas by FMUSP. In 68% of the samples, the antibodies present in the serum were able to bind to the peptide P44, which is present in the RBD of the protein tip.

Computer simulations were carried out to understand how antibodies bind in this region found by the researchers. The RBD information from the two variants and the ancestral virus has been crossed with that of the monoclonal antibody REGN10933, which is known to bind to the immunodominant region and is currently in clinical trials for the treatment of Covid-19. The computer carries out what is known as a neutralization prediction, ie it estimates the ability of antibodies to neutralize the virus.

In the simulations, the prediction of neutralization against the ancestral virus was complete and somewhat lower for the P.1 variant. In the South African variant, however, there was a drastic decrease in the prediction of neutralization, which confirms what an article published by scientists dismissed by Americans just before the Brazilian submission of the article.

For the group headed by USP, the link in B.1.351 does not occur, since one of their mutations is precisely the exchange of the amino acid lysine for asparagine, which goes through the process of glycosylation. This change would likely account for the low estimate of the neutralization of the South African variant by antibodies generated by infection with the original strain of Sars-CoV-2. The phenomenon of glycosylation has already been observed in the influenza virus of the flu, but has not yet been demonstrated in the case of Sars-CoV-2.

“In the variants P.1 and B.1.351 the RBD mutation consists of only three different amino acids compared to the RBD of the ancestral virus. However, the change seems sufficient to make the Manaus and South Africa variants more transferable. A vaccine that creates antibodies that target the two mutations that both variants have in common, as well as the glycosylated amino acid from B.1.351, will likely be more effective, ”says Santos.

To confirm the hypothesis, the group is now planning in vitro experiments with samples of the P44 peptide with glycosylation in asparagine. The goal is to confirm that antibodies do not actually bind to this amino acid once it is glycosylated. In addition, the researchers received serum from patients who had recovered from P.1 and intend to confirm that these patients’ antibodies even bind to the peptide P44.

Source link

Essa notícia também repercutiu nos veículos:
Portal R7 Galileu online UOL Estadã Quimiweb Pelo Mundo DF NB Notícias São Gonçalo Agora Blog RN Política em Dia Rio Brilhante News Zatum Folha de Sabará online Novo Cantu Notícias TV Diário de Alagoas A Crítica (AM) online Jornal da Ciência online Debate Paraíba Portal Agora Notícias Portal da Feira São Bento em Foco Acontece no RS Verguia Bom Dia Cidade Notícias Coluna Supinando Esplanada News Consecti - Conselho Nacional de Secretários Estaduais para Assuntos de CT&I Revista Cenarium online Fique informado Portal Altônia Bahia e Região Noticias de Contagem online Pharma Innovation Saense MSN (Brasil) ES360 Portal Você Online Terra Nossa Folha News Saber Atualizado Plantão News (MT) O Sul online O Jiló Foco Cidade Nativa News Tony Show Jornal O candeeiro online 2A+ Farma Acontece Botucatu NewsLab online Jaguariaíva em Foco LabNetwork Guia Viver Bem O Sul Câmara Municipal de São Paulo Agora Região Bom dia Paraiba Folha de Florianópolis Mega Manchete Portal Altônia Portal O Sertão Symplexia Portal Afunilados Alagoas Agora online Alvo Notícias Bahia Jornal BF News Capital Circuito D Circulando Aqui Extra News MS Fatos Locais Giro Notícias Goiás Itaberaba em Foco Jornal A Voz do Povo online (Uberlândia, MG) Jornal Ponta Grossa Laranjeiras News MaisAM Maranhão em Pauta Oficial News Penha News Ponta Porã Digital Portal Curiúva Portal G86 Porto Murtinho Notícias Riacho Notícias Rosário News SouPVH Tribuna Paulista Toni Rodrigues TV Brusque Xingu 230 Jornal A Cidade (Ponta Porã, MS) Folha da Minha Sampa Portal Brasileira Portal Antenados Portal da Enfermagem TV & VC? O Melhor da Cidade Blog 3 Poderes Rádio Uau RBN 94,3 FM InforBahia Portalqn MS Aqui News Notícias da Sua Cidade Metropolitana MS J1 Notícias Jornal Um Só Corpo Grava News - Jornal de Alfenas Imperlove Portal Chapada Grande Hoje Bahia MA217 Sudoeste MSnews Revista Metropolitana Minha Pará de Minas O Servidor Público Rádio Saj Net Garanhuns Notícias Diário Caiobá Cidade Notícia Jornal da Cidade Online LauroCITY Folha Impacto Giro 7 Garanhuns Notícias Giro Notícias Goiás Grupo News Paraná Conexão Cidade Diário de Cuiabá online Diário D4 Notícias MaisAM Cidade Notícia Conexão Cidade Relato News Lucas em foco Acre ao Vivo Porto Estrela News Portal VDL Portal Paripiranguense Portal do Trairi Portal Manhumirim Rádio Atalaia FM 87,9 Campo Belo em Foco Página de Polícia Osvaldo Batista Diário D4 Notícias Relata Bahia Cabreúva Online Brasil de Olho Poder e Notícia A Voz dos Municípios (Laranjeiras, Sergipe) online Oeste Ao Vivo Oeste 360 Grupo News Paraná LauroCITY Rádio Leme FM RV News TV Interbam Click Nova Olímpia