RESUMEN
Tetracycline (TET) has been widely used in the treatment of Streptococcus suis (S. suis) infection. However, it was found that the efficacy of many antibiotics in S. suis decreased significantly, especially tetracycline. In this study, GML-12 (a novel pleuromutilin derivative) was used in combination with TET against 12 S. suis isolates. In the checkerboard assay, the TET/GML-12 combination exhibited synergistic and additive effects against S. suis isolates (n = 12). In vitro time-killing assays and in vivo therapeutic experiments were used to confirm the synergistic effect of the TET/GML-12 combination against S. suis strains screened based on an FICI ≤ 0.5. In time-killing assays, the TET/GML-12 combination showed a synergistic effect or an additive effect against three isolates with a bacterial reduction of over 2.4-log10 CFU/mL compared with the most active monotherapy. Additionally, the TET/GML-12 combination displayed potent antimicrobial activity against four isolates in a mouse thigh infection model. These results suggest that the TET/GML-12 combination may be a potential therapeutic strategy for S. suis infection.
Asunto(s)
Antibacterianos/administración & dosificación , Diterpenos/administración & dosificación , Compuestos Policíclicos/administración & dosificación , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus suis/efectos de los fármacos , Tetraciclina/administración & dosificación , Animales , Antibacterianos/toxicidad , Zoonosis Bacterianas/tratamiento farmacológico , Zoonosis Bacterianas/microbiología , Modelos Animales de Enfermedad , Diterpenos/toxicidad , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Humanos , Técnicas In Vitro , Ratones , Ratones Endogámicos ICR , Pruebas de Sensibilidad Microbiana , Neutropenia/tratamiento farmacológico , Neutropenia/microbiología , Compuestos Policíclicos/toxicidad , Infecciones Estreptocócicas/microbiología , Streptococcus suis/aislamiento & purificación , Porcinos , Enfermedades de los Porcinos/tratamiento farmacológico , Enfermedades de los Porcinos/microbiología , PleuromutilinasRESUMEN
Since 2019, the novel coronavirus (SARS-CoV-2) has caused significant morbidity and millions of deaths worldwide. The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 and its variants, has further highlighted the urgent need for the development of effective therapeutic agents. Currently, the highly conserved and broad-spectrum nature of main proteases (Mpro) renders them of great importance in the field of inhibitor study. In this study, we categorize inhibitors targeting Mpro into three major groups: mimetic, nonmimetic, and natural inhibitors. We then present the research progress of these inhibitors in detail, including their mechanism of action, antiviral activity, pharmacokinetic properties, animal experiments, and clinical studies. This review aims to provide valuable insights and potential avenues for the development of more effective antiviral drugs against SARS-CoV-2.