Tracking the relevant researches of CADD drug development against COVID-19
Trovafloxacin is a broad spectrum antibiotic that has been commonly marketed under the brand name Trovan by Pfizer. It exerts its antibacterial activity by inhibiting the uncoiling of supercoiled DNA in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It was shown to be more effective against Gram-positive bacteria than Gram-negative bacteria when compared to previous fluoroquinolones. Due to its hepatotoxic potential, trovafloxacin was withdrawn from the market. [DrugBank]
DNA gyrase subunit A (Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)); DNA topoisomerase 4 subunit A (Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)); DNA topoisomerase 2-alpha (Humans) [DrugBank]
Trovafloxacin is a broad spectrum antibiotic that inhibits DNA supercoiling in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It is not used widely due to the risk of hepatotoxicity. It tends to have better gram-positive bacterial coverage and less gram-negative coverage than the previous fluoroquinolones. Mechanism of action of fluoroquinolones including trovafloxacin is different from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines. Therefore fluoroquinolones may be active against pathogens that are resistant to these antibiotics. There is no cross-resistance between trovafloxacin and the mentioned classes of antibiotics. The overall results obtained from in vitro synergy studies, testing combinations of trovafloxacin with beta-lactams and aminoglycosides, indicate that synergy is strain specific and not commonly encountered. This agrees with results obtained previously with other fluoroquinolones. Resistance to trovafloxacin in vitro develops slowly via multiple-step mutation in a manner similar to other fluoroquinolones. Resistance to trovafloxacin in vitro occurs at a general frequency of between 1x10-7 to 10-10. Although cross-resistance has been observed between trovafloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to trovafloxacin. [DrugBank]
Tips: Click on the link to jump to the 'SwissTargetPrediction' webserver. Select the species of 'Homo sapiens', and then paste the SMILES of Trovafloxacin in the SMILES input box.
Tips: Click on the link to jump to the 'CB-Dock' webserver. Upload the structure file of target predicted by 'SwissTargetPrediction' and the 2D/3D structure file of Trovafloxacin to perform blind docking.