Metal-Organic Frameworks: Unconventional Nanoweapons against COVID

Abstract

The SARS-CoV-2 (COVID-19) pandemic outbreak led to enormous social and economic repercussions worldwide, felt even to this date, making the design of new therapies to combat fast-spreading viruses an imperative task. In the face of this, diverse cutting-edge nanotechnologies have risen as promising tools to treat infectious diseases such as COVID-19, as well as challenging illnesses such as cancer and diabetes. Aside from these applications, nanoscale metal-organic frameworks (nanoMOFs) have attracted much attention as novel efficient drug delivery systems for diverse pathologies. However, their potential as anti-COVID-19 therapeutic agents has not been investigated. Herein, we propose a pioneering anti-COVID MOF approach by studying their potential as safe and intrinsically antiviral agents through screening various nanoMOF. The iron(III)-trimesate MIL-100 showed a noteworthy antiviral effect against SARS-CoV-2 at the micromolar range, ensuring a high biocompatibility profile (90% of viability) in a real infected human cellular scenario. This research effectively paves the way toward novel antiviral therapies based on nanoMOFs, not only against SARS-CoV-2 but also against other challenging infectious and/or pulmonary diseases.

Keywords: COVID-19; antiviral; metal−organic frameworks; nanomedicines; therapy.

Figure 1

NanoMOF antiviral activity in SARS-CoV-2 infected A549-ACE2 cells. Infection efficacy (%, green bars) and biocompatibility profiles (MTT assays, purple bars; DAPI-dyed cells, blue bars) were plotted after 48 h in the presence of the indicated doses (μg·mL^–1) of MIL-100(Fe), MIL-88B-NH₂(Fe), MIL-101-NH₂(Fe), UiO-66-NH₂(Zr), SU-102(Zr), and SU-101(Bi). Data are shown as mean ± standard deviation (SD) of three different experiments in triplicates (n = 9). Statistical significance was determined using ANOVA and Dunnetts post hoc method.

Figure 2

Precursor antiviral activity in SARS-CoV-2 infected A549-ACE2 cells.

Figure 3

NanoMOF stability. (A) Chemical: Linker release [H₃BTC, NH₂BDC; % by high-performance liquid chromatography (HPLC)] in supplemented DMEM at 37 °C after 48 h. Data are shown as mean ± SD with three replicates per experiment. SU-102(Zr) and SU-101(Bi) did not show linker release; (B) Colloidal: Size (nm) variation in supplemented DMEM at 37 °C after 48 h.