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Structural analysis of SARS-Cov-2 nonstructural protein 1 polymorphisms found in the Brazilian Amazon.
Zanchi, Fernando Berton; Mariúba, Luis André; Nascimento, Valdinete; Souza, Victor; Corado, André; Nascimento, Fernanda; Costa, Ágatha Kelly; Duarte, Débora; Silva, George; Mejía, Matilde; Pessoa, Karina; Gonçalves, Luciana; Brandão, Maria Júlia; Jesus, Michele; Glória, Juliane; Silva, Marineide; Mattos, Tirza; da Costa, Cristiano; Naveca, Felipe Gomes.
  • Zanchi FB; Laboratório de Bioinformática e Química Medicinal, Fundação Oswaldo Cruz, FIOCRUZ, Unidade Rondônia, Porto Velho, RO 76812-245, Brazil.
  • Mariúba LA; Programa de Pós-Graduação em Biologia Experimental, Universidade Federal de Rondônia (UNIR), Porto Velho, RO 76801-059, Brazil.
  • Nascimento V; Instituto Nacional de Epidemiologia na Amazônia Ocidental - EPIAMO, Porto Velho, RO 76812-245, Brazil.
  • Souza V; Programa Multi-institucional de Pós-graduação em Biotecnologia, Universidade Federal do Amazonas (PPGBIOTEC-UFAM), Manaus, AM 69067-005, Brazil.
  • Corado A; Programa de Pós-graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas (PPGIBA-UFAM), Manaus, AM 69067-005, Brazil.
  • Nascimento F; Fundação Oswaldo Cruz, Fiocruz, Instituto Leônidas e Maria Deane (ILMD-FIOCRUZ), Manaus, AM 69057-070, Brazil.
  • Costa ÁK; Fundação Oswaldo Cruz, Fiocruz, Instituto Oswaldo Cruz, Programa de Pós-Graduação em Biologia Celular e Molecular, Rio de Janeiro, RJ 21040-360, Brazil.
  • Duarte D; Fundação Oswaldo Cruz, Fiocruz, Instituto Leônidas e Maria Deane (ILMD-FIOCRUZ), Manaus, AM 69057-070, Brazil.
  • Silva G; Fundação Oswaldo Cruz, Fiocruz, Instituto Oswaldo Cruz, Programa de Pós-Graduação em Biologia Celular e Molecular, Rio de Janeiro, RJ 21040-360, Brazil.
  • Mejía M; Rede Genômica de Vigilância em Saúde do Estado do Amazonas, Manaus, AM 69057-070, Brazil.
  • Pessoa K; Fundação Oswaldo Cruz, Fiocruz, Instituto Leônidas e Maria Deane (ILMD-FIOCRUZ), Manaus, AM 69057-070, Brazil.
  • Gonçalves L; Fundação Oswaldo Cruz, Fiocruz, Instituto Oswaldo Cruz, Programa de Pós-Graduação em Biologia Celular e Molecular, Rio de Janeiro, RJ 21040-360, Brazil.
  • Brandão MJ; Rede Genômica de Vigilância em Saúde do Estado do Amazonas, Manaus, AM 69057-070, Brazil.
  • Jesus M; Fundação Oswaldo Cruz, Fiocruz, Instituto Leônidas e Maria Deane (ILMD-FIOCRUZ), Manaus, AM 69057-070, Brazil.
  • Glória J; Fundação Oswaldo Cruz, Fiocruz, Instituto Oswaldo Cruz, Programa de Pós-Graduação em Biologia Celular e Molecular, Rio de Janeiro, RJ 21040-360, Brazil.
  • Silva M; Fundação Oswaldo Cruz, Fiocruz, Instituto Leônidas e Maria Deane (ILMD-FIOCRUZ), Manaus, AM 69057-070, Brazil.
  • Mattos T; Fundação Oswaldo Cruz, Fiocruz, Instituto Leônidas e Maria Deane, Programa de Pós-Graduação em Biologia da Interação Patógeno-Hospedeiro, Manaus, AM 69057-070, Brazil.
  • da Costa C; Fundação Oswaldo Cruz, Fiocruz, Instituto Leônidas e Maria Deane (ILMD-FIOCRUZ), Manaus, AM 69057-070, Brazil.
  • Naveca FG; Fundação Oswaldo Cruz, Fiocruz, Instituto Leônidas e Maria Deane (ILMD-FIOCRUZ), Manaus, AM 69057-070, Brazil.
Exp Biol Med (Maywood) ; 246(21): 2332-2337, 2021 11.
Article in English | MEDLINE | ID: covidwho-1507096
ABSTRACT
The coronavirus disease COVID-19 has been the cause of millions of deaths worldwide. Among the SARS-CoV-2 proteins, the non-structural protein 1 (NSP1) has great importance during the virus infection process and is present in both alpha and beta-CoVs. Therefore, monitoring of NSP1 polymorphisms is crucial in order to understand their role during infection and virus-induced pathogenicity. Herein, we analyzed how mutations detected in the circulating SARS-CoV-2 in the population of the city of Manaus, Amazonas state, Brazil could modify the tertiary structure of the NSP1 protein. Three mutations were detected in the SARS-CoV-2 NSP1 gene deletion of the amino acids KSF from positions 141 to 143 (delKSF), SARS-CoV-2, lineage B.1.195; and two substitutions, R29H and R43C, SARS-CoV-2 lineage B.1.1.28 and B.1.1.33, respectively. The delKSF was found in 47 samples, whereas R29H and R43C were found in two samples, one for each mutation. The NSP1 structures carrying the mutations R43C and R29H on the N-terminal portion (e.g. residues 10 to 127) showed minor backbone divergence compared to the Wuhan model. However, the NSP1 C-terminal region (residues 145 to 180) was severely affected in the delKSF and R29H mutants. The intermediate variable region (residues 144 to 148) leads to changes in the C-terminal region, particularly in the delKSF structure. New investigations must be carried out to analyze how these changes affect NSP1 activity during the infection. Our results reinforce the need for continuous genomic surveillance of SARS-CoV-2 to better understand virus evolution and assess the potential impact of the viral mutations on the approved vaccines and future therapies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Nonstructural Proteins / SARS-CoV-2 / COVID-19 Type of study: Observational study Topics: Vaccines Limits: Humans Country/Region as subject: South America / Brazil Language: English Journal: Exp Biol Med (Maywood) Journal subject: Biology / Physiology / Medicine Year: 2021 Document Type: Article Affiliation country: 15353702211021348

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Nonstructural Proteins / SARS-CoV-2 / COVID-19 Type of study: Observational study Topics: Vaccines Limits: Humans Country/Region as subject: South America / Brazil Language: English Journal: Exp Biol Med (Maywood) Journal subject: Biology / Physiology / Medicine Year: 2021 Document Type: Article Affiliation country: 15353702211021348