Abstract – Publication

Pyronaridine protects against SARS-CoV-2 infection in mouse.
PUHL, Ana C.; GOMES, Giovanni Freitas; DAMASCENO, Samara; GODOY, Andre Schutzer de; NOSKE, Gabriela Dias; NAKAMURA, Aline Minali; OLIVEIRA, Victor Gawriljuk Ferraro; FERNANDES, Rafaela Sachetto; MONAKHOVA, Natalia; RIABOVA, Olga; LANE, Thomas R.; MAKAROV, Vadim; VERAS, Flávio Protásio; BATAH, Sabrina Setembre; FABRO, Alexandre Todorovic; OLIVA, Glaucius; CUNHA, Fernando de Queiroz; ALVES FILHO, José Carlos Farias; CUNHA, Thiago Mattar; EKINS, Sean.
Abstract: 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.
ACS Infectious Diseases
v. 8, n. 6, p. 1147-1160 - Ano: 2022
Fator de Impacto: 5,578
    @article={003081056,author = {PUHL, Ana C.; GOMES, Giovanni Freitas; DAMASCENO, Samara; GODOY, Andre Schutzer de; NOSKE, Gabriela Dias; NAKAMURA, Aline Minali; OLIVEIRA, Victor Gawriljuk Ferraro; FERNANDES, Rafaela Sachetto; MONAKHOVA, Natalia; RIABOVA, Olga; LANE, Thomas R.; MAKAROV, Vadim; VERAS, Flávio Protásio; BATAH, Sabrina Setembre; FABRO, Alexandre Todorovic; OLIVA, Glaucius; CUNHA, Fernando de Queiroz; ALVES FILHO, José Carlos Farias; CUNHA, Thiago Mattar; EKINS, Sean.},title={Pyronaridine protects against SARS-CoV-2 infection in mouse},journal={ACS Infectious Diseases},note={v. 8, n. 6, p. 1147-1160},year={2022}}

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