Why have nanotechnologies been underutilized in the global uprising against the coronavirus pandemic?

Abstract

Prior research on nanotechnologies in diagnostics, prevention and treatment of coronavirus infections is reviewed. Gold nanoparticles and semiconductor quantum dots in colorimetric and immunochromatographic assays, silica nanoparticles in the polymerase chain reaction and spike protein nanospheres as antigen carriers and adjuvants in vaccine formulations present notable examples in diagnostics and prevention, while uses of nanoparticles in coronavirus infection treatments have been merely sporadic. The current absence of antiviral therapeutics that specifically target human coronaviruses, including SARS-CoV-2, might be largely due to the underuse of nanotechnologies. Elucidating the interface between nanoparticles and coronaviruses is timely, but presents the only route to the rational design of precisely targeted therapeutics for coronavirus infections. Such a fundamental approach is also a viable prophylaxis against future pandemics of this type.

Keywords: COVID-19; infectious disease; interface; nanoparticle; nanotechnology; vaccine.

Figure 1.. Bibliographic analysis.

Total annual number of publications listed in the United States National Library of Medicine and containing the following keywords: ‘nanoparticles’ and either ‘cancer’ or ‘viral’; (A) ‘hepatitis’ or ‘coronavirus’; (B) ‘H1N1’ or ‘MERS-CoV’ (C). Search was performed at https://www.ncbi.nlm.nih.gov/pubmed/ on 14 March 2020. Total number of patents filed in the United States Patent Office and containing the word ‘nanoparticles’, the word ‘coronavirus’ or both of these words in the claims for the period 1976–2020 (D). Search was performed at https://patft.uspto.gov/netahtml/PTO/search-adv.htm using the ‘aclm/(keyword and keyword)’ operator on 15 March 2020. MERS-CoV: Middle East respiratory syndrome-related coronavirus.

Figure 2.. Nanotechnologies in coronavirus research.

(A) Transmission electron micrograph of SARS-CoV viral particles entering a Vero E6 host cell by binding to the cell surface receptor (upper left arrow), then having their envelopes fuse with the cell membrane (central arrow) and nucleocapsids enter the cell (arrowhead). Bar is 100 nm. Reproduced with permission from [53], licensed with CC BY 3.0. (B) Poly(D,L-lactide-co-glycolide) nanoparticles loaded with inactive PEDV antigens (PLGA-KAg) increasing IgG and neutralizing antibody titers in sows relative to the titers in sows treated with saline and sows inoculated with the antigen alone (KAg and 201-KAg). Bar is 100 nm. Reproduced with permission from [68] © Elsevier (2017). (C) Schematic representation of a protein cage nanoparticle showing individual protein subunits and the survival of mice infected with SARS-CoV after the treatment with saline (empty triangles) or with the protein cage nanoparticles (black squares). Reproduced with permission from [83], licensed with CC BY 3.0. (D) Toluidine blue staining of the fore paws of the vehicle control mice showing moderate inflammation and cartilage damage with moderate pannus and bone resorption in all the joints and of mice treated with the SARS-CoV-derived peptide MWKTPTLKYFG (MG11) delivered with spherical high-density lipopeptide nanoparticles, showing no inflammation and minimal cartilage damage. Arrows identify affected joints. Tipped W denotes the wrist. Reproduced with permission from [112], licensed with CC BY 4.0. PBS: Phosphate-buffered saline; PEDV: Porcine epidemic diarrhea virus; PLGA: Poly(D,L-lactide-co-glycolide); sHDL: Spherical high-density lipopeptide nanoparticles.