Nanotechnology advances in pathogen- and host-targeted antiviral delivery: multipronged therapeutic intervention for pandemic control

Abstract

The COVID-19 pandemic's high mortality rate and severe socioeconomic impact serve as a reminder of the urgent need for effective countermeasures against viral pandemic threats. In particular, effective antiviral therapeutics capable of stopping infections in its tracks is critical to reducing infection fatality rate and healthcare burden. With the field of drug delivery witnessing tremendous advancement in the last two decades owing to a panoply of nanotechnology advances, the present review summarizes and expounds on the research and development of therapeutic nanoformulations against various infectious viral pathogens, including HIV, influenza, and coronaviruses. Specifically, nanotechnology advances towards improving pathogen- and host-targeted antiviral drug delivery are reviewed, and the prospect of achieving effective viral eradication, broad-spectrum antiviral effect, and resisting viral mutations are discussed. As several COVID-19 antiviral clinical trials are met with lackluster treatment efficacy, nanocarrier strategies aimed at improving drug pharmacokinetics, biodistributions, and synergism are expected to not only contribute to the current disease treatment efforts but also expand the antiviral arsenal against other emerging viral diseases.

Keywords: Antiviral state; Antivirals; COVID-19; Drug delivery; Host-targeted antiviral; Nanodecoy; Nanoparticles; Nanosponge.

Fig. 1

A schematic representation of virus replication step, antiviral drugs aimed at distinctive stages of viral replication, and gain of feature with nanocarriers. Created with BioRender

Fig. 2

Pathogen-targeted nanoformulation classified into four categories, including A long-acting Cabotegravir prodrug fatty acid esters (FAE) nanorod, adapted from [47] capable of year-long drug release; B tissue targeting poly(ε-caprolactone) (PCL) nanoparticles capable of multivalent cell targeting, adapted from [48]; C combinational anti-HIV PLGA nanoparticle integrating current standard of care ART therapy, adapted from [37]; and D RNA-based anti-Ebola lipid nanoparticle that has shown therapeutic efficacy in non-human primates, adapted from [43]

Fig. 3

A Schematic of endosome acidification inhibition for halting cytosolic entry of viruses. Nanoformulation in this category include B chloroquine nanoliposomes, adapted from  [82] (copyright 2019 with permission from Elsevier), C silicon nanoparticles contains SaliPhe, adapted from  [83], and D diphyllin encapsulated PEG-PLGA nanoparticles, adapted from [41], copyright 2019 with permission from Dove Medical Press

Fig. 4

A The interferon induction pathways and its downstream functions in inhibiting viral replication. Nanoformulation that inhibit viral replications through the induction of cellular antiviral state include B IFN-γ liposomes (adapted from [100]), C IFN-α polymeric nanoparticles (adapted from [97]), D STING agonist nanoparticles (adapted from [108]), and E CpG-loaded polymeric nanoshell. Adapted from [109], copyright 2020 with permission from Dove Medical Press

Fig. 5

A Schematic presentation of biomimetic nanoparticle designs for targeting both virus and virally infected host cells. Examples of cell membrane-cloaked nanoparticles for specific virus targeting include B red blood cell membrane-coated particles for influenza targeting [127], C CD4 T cell membrane-coated particles for HIV targeting [133], and D mosquito cell membrane-wrapped particles for Zika virus targeting [138]. TEM pictures in the insets are cited with permission from [121, 127]. Copyright 2017 American Chemical Society