rolitetracycline and Disease-Models--Animal

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

The myocardial infarct induced by isoproterenol in spontaneously hypertensive rats accumulates higher activities of 99mTc-PM tetracycline compared with the cardiac infarct in normotensive rats caused by the same method. The isoproterenol model of the myocardial necrosis was induced in intact rats without opening the thorax and is a convenient method for experimental radioisotope studies.

Topics: Animals; Disease Models, Animal; Female; Hypertension; Isoproterenol; Male; Myocardial Infarction; Myocardium; Necrosis; Organotechnetium Compounds; Radionuclide Imaging; Rats; Rats, Inbred Strains; Rolitetracycline; Technetium

A technique for inducing pneumococcal meningitis in mice and a description of the histopathologic changes that accompany this experimentally produced disease are provided in the present report. This infection of mice was investigated to determine whether it could serve as a suitable model for detecting agents that have potential therapeutic utility in bacterial meningitis in man. 21 antibiotics, belonging to six major classes were evaluated for efficacy in the experimental infection. The three most active agents proved to be amoxicillin, cephaloridine, and chlortetracycline. Up to this time, amoxicillin has not been commercially available as an injectable dosage form. However, in view of the compound's outstanding efficacy in the present experiments, it would be desirable to investigate its effectiveness in the naturally occurring disease in man.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Cerebellum; Cerebral Cortex; Chloramphenicol; Chlortetracycline; Demeclocycline; Disease Models, Animal; Erythromycin; Lincomycin; Male; Meningitis, Pneumococcal; Mice; Penicillins; Rolitetracycline; Streptococcus pneumoniae; Tetracycline; Virulence

Topics: Animals; Disease Models, Animal; Male; Microscopy, Electron; Rabbits; Rolitetracycline; Syphilis; Treponema pallidum

Topics: Animals; Bartonella Infections; Chickens; Chlortetracycline; Disease Models, Animal; Oxytetracycline; Rolitetracycline; Tetracycline