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Zika virus (ZIKV), belonging to the family of flaviviruses, is an emerging mosquito-borne pathogen causing microcephaly and other congenital abnormalities in newborns as well as various neurologic pathologies in adults. The climate change and the lifestyle of current societies, involving global mobility, result in a rapid broadening of ZIKV geographic distribution. There are no vaccines or drugs available to protect against or cure the diseases caused by that virus. Our in vitro studies have demonstrated that sodium polyanethole sulfonate (PASNa), a degradable polymer used in various biomedical applications, acts as an efficient ZIKV inhibitor, both in animal and human cells. The mechanistic studies indicated that PASNa bound to the ZIKV particles thus hindering their attachment to the host cells and also interfered in the late steps of viral replication. PASNa is characterized by very low cytotoxicity and its antiviral activity can be achieved at a concentration much lower than that at which its anticoagulant activity has to be considered. Isothermal titration calorimetry (ITC) studies have shown that the interaction of PASNa with human serum albumin (HSA), the most abundant blood protein, is the endothermic, entropydriven process resulting in the formation of stoichiometric (1:1) PASNa-HSA complexes with a hydrodynamic diameter of 8.8 ± 0.8 nm and zeta potential (ζ) equal to -21.3 mV. The analysis of CD spectra indicated that PASNa did not significantly affect the HSA secondary structure on binding to that protein. [ABSTRACT FROM AUTHOR]