Reactive Oxygen Species‐Regulating Polymersome as an Antiviral Agent against Influenza Virus

Abstract

Reactive oxygen species (ROS) produced during mitochondrial oxidative phosphorylation play an important role as signal messengers in the immune system and also regulate signal transduction. ROS production, initiated as a consequence of microbial invasion, if generated at high levels, induces activation of the MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinase) pathway to promote cell survival and proliferation. However, viruses hijack the host cells' pathways, causing biphasic activation of the MEK/ERK cascade. Thus, regulation of ROS leads to concomitant inhibition of virus replication. In the present study, poly(aniline-co-pyrrole) polymerized nanoregulators (PASomes) to regulate intracellular ROS levels are synthesized, exploiting their oxidizing-reducing characteristics. Poly(aniline-co-pyrrole) embedded within an amphiphilic methoxy polyethylene glycol-block-polyphenylalanine copolymer (mPEG-b-pPhe) are used. It is demonstrated that the PASomes are water soluble, biocompatible, and could control ROS levels successfully in vitro, inhibiting viral replication and cell death. Furthermore, the effects of homopolymerized nanoregulators (polypyrrole assembled with mPEG-b-pPhe or polyaniline assembled with mPEG-b-pPhe) are compared with those of the PASomes. Consequently, it is confirmed that the PASomes can regulate intracellular ROS levels successfully and suppress viral infection, thereby increasing the cell survival rate.

Glycyrrhizic‐Acid‐Based Carbon Dots with High Antiviral Activity by Multisite Inhibition Mechanisms

“…Reducing the ROS level by their inhibitors can inhibit virus proliferation. It is reported that the intracellular ROS levels can be successfully regulated to suppress viral infection by embedding poly(aniline‐co‐pyrrole) within an amphiphilic methoxy polyethylene glycol‐block‐polyphenylalanine copolymer 68. Another study has shown that silver nanoparticle‐based codelivery of oseltamivir could remarkably inhibit the accumulation of ROS and activate the signaling pathways of AKT and p53 phosphorylation to inhibit H1N1 influenza virus infection 69.…”

COVID-19 infection and nanomedicine applications for development of vaccines and therapeutics: An overview and future perspectives based on polymersomes

“…Polymersomes were designed to mimic the cell structure with an aqueous cavity, and they showed a high capacity for drug loading, especially as a co-delivery system upon loading hydrophobic and hydrophilic drugs in their exterior layers and cores, respectively ( Kim et al, 2013 ; Li et al, 2016 ). Polymersomes have recently been exploited not only as vehicles for the delivery of various therapeutic compounds ( Chun et al, 2018 ), but also based on their potential to regulate ROS ( Kim et al, 2017 ). Owing to their immunogenic properties ( Webster et al, 2013 ), polymersomes could play a vital role in improving subunit vaccines and therapeutics delivery against COVID-19 infection.…”

Nano-based approaches in the development of antiviral agents and vaccines

“…Carbon dots established from PEG-diamine and ascorbic acid induce interferon-α (IFN-α) production and the expression of IFN-stimulating genes in host cells, resulting in powerful antiviral responses and the inhibition of the replication of pseudorabies virus (PRV) and porcine reproductive and respiratory syndrome virus (PRRS) [ 59 ]. As an organic nanomaterial, poly(aniline- co -pyrrole) polymerized nanoregulators (PASomes) control intracellular reactive oxygen species (ROS) levels in vitro to inhibit viral replication and cell death [ 60 ]. Since certain viruses can hijack host cell pathways to cause the biphasic activation of the MEK/ERK cascade, which improves viral replication [ 61 ], investigations of the precise regulation of the intracellular response to viral infection are still warranted when designing antiviral agents.…”