Poly(ethylene glycol) -block- poly(sodium 4-styrenesulfonate) Copolymers as Efficient Zika Virus Inhibitors: In Vitro Studies

Paweł Botwina; Magdalena Obłoza; Piotr Bonarek; Krzysztof Szczubiałka; Krzysztof Pyrć; Maria Nowakowska

doi:10.1021/acsomega.2c07610

Poly(ethylene glycol) -block- poly(sodium 4-styrenesulfonate) Copolymers as Efficient Zika Virus Inhibitors: In Vitro Studies

ACS Omega. 2023 Feb 9;8(7):6875-6883. doi: 10.1021/acsomega.2c07610. eCollection 2023 Feb 21.

Authors

Paweł Botwina^{1

2}, Magdalena Obłoza³, Piotr Bonarek⁴, Krzysztof Szczubiałka³, Krzysztof Pyrć¹, Maria Nowakowska³

Affiliations

¹ Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland.
² Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
³ Department of Physical Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
⁴ Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.

Abstract

A series of poly(ethylene glycol)-block-poly(sodium 4-styrenesulfonate) (PEG-b-PSSNa) copolymers were synthesized, and their antiviral activity against Zika virus (ZIKV) was determined. The polymers inhibit ZIKV replication in vitro in mammalian cells at nontoxic concentrations. The mechanistic analysis revealed that the PEG-b-PSSNa copolymers interact directly with viral particles in a zipper-like mechanism, hindering their interaction with the permissive cell. The antiviral activity of the copolymers is well-correlated with the length of the PSSNa block, indicating that the copolymers' ionic blocks are biologically active. The blocks of PEG present in copolymers studied do not hinder that interaction. Considering the practical application of PEG-b-PSSNa and the electrostatic nature of the inhibition, the interaction between the copolymers and human serum albumin (HSA) was evaluated. The formation of PEG-b-PSSNa-HSA complexes in the form of negatively charged nanoparticles well-dispersed in buffer solution was observed. That observation is promising, given the possible practical application of the copolymers.