Pyronaridine Protects against SARS-CoV-2 Infection in Mouse

• DOI: 10.1021/acsinfecdis.2c00091
• Publication Date: 2022-05-24T21:58:27Z
• Authors: Ana C. Puhl; Giovanni F. Gomes; Samara Damasceno; Andre S. Godoy; Gabriela D. Noske; Aline M. Nakamura; Victor O. Gawriljuk; Rafaela S. Fernandes; Natalia Monakhova; Olga Riabova; Thomas R. Lane; Vadim Makarov; Flavio P. Veras; Sabrina S. Batah; Alexandre T. Fabro; Glaucius Oliva; Fernando Q. Cunha; José C. Alves-Filho; Thiago M. Cunha; Sean Ekins
• Keywords: IC50; Coronavirus; Antiviral drug

There are currently relatively few small-molecule antiviral drugs that 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 Ebola. We evaluated three molecules we had previously identified computationally with activity Ebola and Marburg pyronaridine, inhibited the SARS-CoV-2 replication in A549-ACE2 cells. The vivo efficacy pyronaridine has now been assessed a K18-hACE transgenic mouse model COVID-19. Pyronaridine treatment demonstrated statistically significant reduction viral load lungs SARS-CoV-2-infected mice, reducing lung pathology, also associated levels pro-inflammatory cytokines/chemokine cell infiltration. PLpro vitro (IC50 1.8 μM) without any effect on Mpro, indicating possible molecular mechanism involved ability to inhibit replication. have generated several analogs assist understanding structure relationship inhibition. Our results indicate potential therapeutic candidate