Antiviral Mechanisms of Microbial Biosurfactants: A Narrative Review of Current Evidence and Therapeutic Potential

Context: Biosurfactants are eco-friendly biomolecules produced by microorganisms that exhibit emerging antiviral properties. The rise of drug-resistant viruses underscores an urgent need for novel therapeutic agents. This review assesses current knowledge of the antiviral mechanisms of microbial biosurfactants, identifies the major biosurfactant classes with antiviral activity, and delineates key challenges and research priorities for clinical translation. Evidence Acquisition: A literature search was conducted in PubMed, Scopus, and Google Scholar to identify peer-reviewed articles published up to 2026, focusing on biosurfactants with documented antiviral activity and mechanistic studies. Results: Lipopeptides (surfactin, iturin, fengycin) and glycolipids (sophorolipids, rhamnolipids, trehalolipids) are the most extensively studied antiviral biosurfactants. Four primary mechanisms were identified: (i) direct virucidal disruption of viral lipid envelopes via hydrophobic insertion and micellization, active against enveloped viruses including SARS-CoV-2, herpes simplex virus (HSV), and influenza; (ii) inhibition of viral attachment by blocking glycoprotein spikes (SARS-CoV-2 S protein, HSV glycoprotein D) or masking host cell receptors (ACE2, NTCP); (iii) suppression of viral replication through polymerase and protease inhibition (e.g., hepatitis C virus [HCV] NS3, SARS-CoV-2 3CL protease); and (iv) immunomodulation via cytokine enhancement and γδ T-cell proliferation. Notably, the polymerase/protease inhibition mechanism has been reported primarily in two studies from the same research group and has not been generalized to other biosurfactants. Despite promising in vitro activity, reported potency values vary substantially across biosurfactants and experimental assay systems, and clinical translation remains absent owing to production costs, batch variability, limited in vivo data, and formulation challenges. Notably, only one in vivo study has been reported to date, and no clinical investigations exist, underscoring a major translational gap. Conclusions: Biosurfactants offer mechanistically diverse, potentially environmentally sustainable antiviral strategies that may mitigate drug resistance. Priority research directions include elucidating structure–activity relationships, developing standardized production platforms, advancing formulation technologies, and conducting rigorous preclinical evaluations to bridge the gap between laboratory discovery and clinical application.