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Pyronaridine Protects against SARS-CoV-2 Infection in Mouse.
Puhl, Ana C; Gomes, Giovanni F; Damasceno, Samara; Godoy, Andre S; Noske, Gabriela D; Nakamura, Aline M; Gawriljuk, Victor O; Fernandes, Rafaela S; Monakhova, Natalia; Riabova, Olga; Lane, Thomas R; Makarov, Vadim; Veras, Flavio P; Batah, Sabrina S; Fabro, Alexandre T; Oliva, Glaucius; Cunha, Fernando Q; Alves-Filho, José C; Cunha, Thiago M; Ekins, Sean.
Afiliación
  • Puhl AC; Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, North Carolina 27606, United States.
  • Gomes GF; Center for Research in Inflammatory Diseases (CRID), Ribeirao Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto 14049-900, São Paulo, Brazil.
  • Damasceno S; Center for Research in Inflammatory Diseases (CRID), Ribeirao Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto 14049-900, São Paulo, Brazil.
  • Godoy AS; Institute of Physics of Sao Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, Sao Carlos 13563-120, Brazil.
  • Noske GD; Institute of Physics of Sao Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, Sao Carlos 13563-120, Brazil.
  • Nakamura AM; Institute of Physics of Sao Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, Sao Carlos 13563-120, Brazil.
  • Gawriljuk VO; Institute of Physics of Sao Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, Sao Carlos 13563-120, Brazil.
  • Fernandes RS; Institute of Physics of Sao Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, Sao Carlos 13563-120, Brazil.
  • Monakhova N; Research Center of Biotechnology RAS, Leninsky prospect, 33, Building 2, 119071 Moscow, Russia.
  • Riabova O; Research Center of Biotechnology RAS, Leninsky prospect, 33, Building 2, 119071 Moscow, Russia.
  • Lane TR; Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, North Carolina 27606, United States.
  • Makarov V; Research Center of Biotechnology RAS, Leninsky prospect, 33, Building 2, 119071 Moscow, Russia.
  • Veras FP; Center for Research in Inflammatory Diseases (CRID), Ribeirao Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto 14049-900, São Paulo, Brazil.
  • Batah SS; Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto 14049-900, São Paulo, Brazil.
  • Fabro AT; Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto 14049-900, São Paulo, Brazil.
  • Oliva G; Institute of Physics of Sao Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, Sao Carlos 13563-120, Brazil.
  • Cunha FQ; Center for Research in Inflammatory Diseases (CRID), Ribeirao Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto 14049-900, São Paulo, Brazil.
  • Alves-Filho JC; Center for Research in Inflammatory Diseases (CRID), Ribeirao Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto 14049-900, São Paulo, Brazil.
  • Cunha TM; Center for Research in Inflammatory Diseases (CRID), Ribeirao Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto 14049-900, São Paulo, Brazil.
  • Ekins S; Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, North Carolina 27606, United States.
ACS Infect Dis ; 8(6): 1147-1160, 2022 06 10.
Article en En | MEDLINE | ID: mdl-35609344
There are currently relatively few small-molecule antiviral drugs that are either approved or emergency-approved for use against severe acute respiratory coronavirus 2 (SARS-CoV-2). One of these is remdesivir, which was originally repurposed from its use against Ebola. We evaluated three molecules we had previously identified computationally with antiviral activity against Ebola and Marburg and identified pyronaridine, which inhibited the SARS-CoV-2 replication in A549-ACE2 cells. The in vivo efficacy of pyronaridine has now been assessed in a K18-hACE transgenic mouse model of COVID-19. Pyronaridine treatment demonstrated a statistically significant reduction of viral load in the lungs of SARS-CoV-2-infected mice, reducing lung pathology, which was also associated with significant reduction in the levels of pro-inflammatory cytokines/chemokine and cell infiltration. Pyronaridine inhibited the viral PLpro activity in vitro (IC50 of 1.8 µM) without any effect on Mpro, indicating a possible molecular mechanism involved in its ability to inhibit SARS-CoV-2 replication. We have also generated several pyronaridine analogs to assist in understanding the structure activity relationship for PLpro inhibition. Our results indicate that pyronaridine is a potential therapeutic candidate for COVID-19.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fiebre Hemorrágica Ebola / Tratamiento Farmacológico de COVID-19 Límite: Animals Idioma: En Revista: ACS Infect Dis Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fiebre Hemorrágica Ebola / Tratamiento Farmacológico de COVID-19 Límite: Animals Idioma: En Revista: ACS Infect Dis Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos