Reviving the past for a healthier future: ancient molecules and remedies as a solution to the antibiotic crisis

Options to combat bacterial infections are becoming scarce. We require innovative approaches to enhance the discovery of effective antimicrobials capable of combating bacteria resistant to multiple or all antibiotics. These methods should either directly eliminate resistant bacteria or indirectly influence their viability by inhibiting their virulence or reducing their resistance to antibiotics. One interesting approach is to analyze ancient remedies used to treat bacterial infections, formulate them, and test them against modern microbes. This field has recently been named "ancientbiotics." This approach allows us to leverage centuries of empirical knowledge accumulated, from traditional medicines across various ancient cultures worldwide. The strategy has already yielded promising formulations to combat the ESKAPE group of nosocomial pathogens. Additionally, molecular de-extinction, which involves genome analysis of extinct species to search for useful antimicrobials, such as peptides, offers another avenue. In this review, we compile the antimicrobial effects of ancient remedies and de-extinct molecules known to modern science and discuss possible new strategies to further harness the potential of past remedies and molecules to fight the rise of superbugs.