Poly(ethylene glycol)<i>-block-</i>poly(sodium\n4‑styrenesulfonate) Copolymers as Efficient Zika Virus Inhibitors: <i>In Vitro</i> Studies

Abstract

A series of poly­(ethylene glycol)-<i>block</i>-poly­(sodium\n4-styrenesulfonate) (PEG-<i>b</i>-PSSNa) copolymers were\nsynthesized, and their antiviral activity against Zika virus (ZIKV)\nwas determined. The polymers inhibit ZIKV replication <i>in vitro</i> in mammalian cells at nontoxic concentrations. The mechanistic analysis\nrevealed that the PEG-<i>b-</i>PSSNa copolymers interact\ndirectly with viral particles in a zipper-like mechanism, hindering\ntheir interaction with the permissive cell. The antiviral activity\nof the copolymers is well-correlated with the length of the PSSNa\nblock, indicating that the copolymers’ ionic blocks are biologically\nactive. The blocks of PEG present in copolymers studied do not hinder\nthat interaction. Considering the practical application of PEG-<i>b</i>-PSSNa and the electrostatic nature of the inhibition,\nthe interaction between the copolymers and human serum albumin (HSA)\nwas evaluated. The formation of PEG-<i>b</i>-PSSNa-HSA complexes\nin the form of negatively charged nanoparticles well-dispersed in\nbuffer solution was observed. That observation is promising, given\nthe possible practical application of the copolymers.