Marine natural products with anti-MRSA activities: promising candidates for antibacterial drug discovery.

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is a global health concern, necessitating the development of new antibacterial drug. Marine natural products (MNPs) with unique structures and significant activities are underexploited sources for the discovery of new antibacterial lead compounds. However, the systematic review focusing on MNPs with anti-MRSA activity is still scarce. This review firstly summarized the anti-MRSA MNPs, including their geographical origin, chemical structures and biological activities, reported from 2014 to July 2025. For a better understanding, these 269 MNPs mainly including polyketides and alkaloids are classified and presented according to their biological origins (marine microorganisms, animals and plants). The preliminary structure-activity relationship and the mechanisms of action of some promising MNPs are also discussed. We found that marine microorganisms of the genera Streptomyces, Penicillium and Aspergillus and the animal sponges were the predominant producers of anti-MRSA MNPs. Strikingly, 80 compounds exhibited more potent anti-MRSA activity than that of the positive control or comparable to that of the positive control. This review highlights the huge potential of MNPs as scaffolds for developing next-generation antibacterial agents to combat MRSA and will inspire the development of novel marine drugs.