Anti-Influenza Strategies Based on Nanoparticle Applications

Abstract

Influenza virus has the potential for being one of the deadliest viruses, as we know from the pandemic's history. The influenza virus, with a constantly mutating genome, is becoming resistant to existing antiviral drugs and vaccines. For that reason, there is an urgent need for developing new therapeutics and therapies. Despite the fact that a new generation of universal vaccines or anti-influenza drugs are being developed, the perfect remedy has still not been found. In this review, various strategies for using nanoparticles (NPs) to defeat influenza virus infections are presented. Several categories of NP applications are highlighted: NPs as immuno-inducing vaccines, NPs used in gene silencing approaches, bare NPs influencing influenza virus life cycle and the use of NPs for drug delivery. This rapidly growing field of anti-influenza methods based on nanotechnology is very promising. Although profound research must be conducted to fully understand and control the potential side effects of the new generation of antivirals, the presented and discussed studies show that nanotechnology methods can effectively induce the immune responses or inhibit influenza virus activity both in vitro and in vivo. Moreover, with its variety of modification possibilities, nanotechnology has great potential for applications and may be helpful not only in anti-influenza but also in the general antiviral approaches.

Keywords: antisense strategies; delivery; influenza; influenza vaccine; influenza virus; inhibition; nanoparticles; nanotechnology; resistance.

Figure 1

Scheme of influenza A virion structure. The virion surface is encrusted with the membrane proteins (hemagglutinin and nucleoprotein) and M2 proton channel proteins. The inner side of the virion is overlaid with M1 matrix protein. The 8 vRNP complexes and multiple copies of nuclear export protein are located in the virion interior.

Figure 2

Schematic representation of different nanotechnology applications in vaccination strategies. The main goals are the stimulation of antibody (Ab) production and lymphocyte (T cell) activation. For this purpose, different vaccination strategies were used: viral antigens immobilized on nanoparticles’ (NPs) surfaces (A); viral self-amplifying mRNA encapsulated in NPs, which replicate inside cells, leading to antigen expression (B); or inactivated virus encapsulated in NPs (C).

Figure 3

Schematic view of nanoparticle (NP) applications in gene silencing strategies. The NPs functionalized with oligonucleotides are used as a delivery system to the specific target locations in cells. Different oligonucleotide strategies are used to inhibit virus replication: blocking of accessible ssRNA regions with antisense oligonucleotides (ASOs) complementary to viral RNA (A); targeted degradation of viral mRNA with siRNAs (B); catalytic hydrolysis of viral RNA with DNAzymes designed to target viral RNA (C).

Figure 4

Schematic representation of anti-influenza drugs delivery via nanoparticles (A–F). Arbidol inhibits the formation of hemagglutinin-sialic acid bonding, and thereby blocks the viral entry (A). Amantadine blocks the viral M2 ion channel in order to disturb the uncoating process (B). Saliphenylhalamide blocks the acidification of endosomes and vRNP releasing (C). Ribavirin inhibits RdRp, thus disturbing vRNP formation and mRNA maturation processes (D). Oseltamivir and zanamivir are neuraminidase inhibitors, which blocks the release of the progeny virions (E and F, respectively). Influenza virus life cycle (1–11). Interaction between HA and sialic-acid followed by membrane fusion and viral entry to the cell (1). Endosome formation (2). Uncoating and vRNP releasing to the cytoplasm after pH changes catalyzed by M2 ion channel (3). vRNP transport to the nucleus (4). Genome replication and mRNA synthesis (5). mRNA maturation catalyzed by RdRp (6). Translation of viral proteins by ER and cytosolic ribosomes (7). Maturation of viral proteins at Golgi (8) followed by transport of the proteins to the nucleus for vRNP formation (9). Transport of vRNP and viral proteins to the cellular membrane for assembly and budding (10). Releasing of the progeny virions (11).