Drug Repositioning for Multiresistant Staphylococcus aureus and Escherichia coli from Pandemic Response Box and Global Health Priority Box of MMV
Daniela S. Gonçalves, Nagela B. S. Silva, Anna L. O. Santos, Sara L. de Souza, Gabriel G. Calefi, Ralciane de P. Menezes, Andreia M. de Oliveira, Ghabriel Honório-Silva, Camila M. de Andrade, Marcos P. O. Almeida, Thales A. M. Fernandes, Bellisa de F. Barbosa, Eloísa A. V. Ferro, Robinson Sabino-Silva, Carlos H. G. MartinsAbstract
The phenomenon of antimicrobial resistance (AMR) can occur naturally through spontaneous mutation without major damage; however, the overuse and misuse of antimicrobials is responsible for millions of deaths annually. The development of new drugs is an expensive and slow process, while repositioning active substances to different biological activities is a cheaper and faster option. The aim of this study was to evaluate the possibility of repositioning 640 known chemical compounds provided by the Medicines for Malaria Venture organization for antibacterial and antibiofilm activities against multidrug-resistant Staphylococcus aureus (ATCC and clinical isolated) and Escherichia coli (ATCC and clinical isolated), their cytotoxicity, and prediction of interaction sites between compounds and bacteria. MMV020752 and MMV1578884 against S. aureus ATCC and MMV1579850 against E. coli ATCC presented the lowest minimum inhibitory concentration (MIC) of 0.019 μM. MMV1578884 presented the lowest minimum inhibitory concentration of biofilm (MICB50) of 0.0095 μM and the lowest inhibitory concentration (IC50) of 0.019 μM against S. aureus ATCC. MMV1578884, MMV1580854, MMV027339, and MMV1634081 maintain the viability of HFF cells above 100% at 10 and 20 μM, and their interactions with bacteria occur in lipid and protein regions. It is concluded that drugs already available on the market or in more advanced clinical stages can be repositioned for other targets, even other microorganisms.