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1.
Small Methods ; 5(5): e2001108, 2021 05.
Article in English | MEDLINE | ID: covidwho-1599126

ABSTRACT

During the global outbreak of COVID-19 pandemic, "cytokine storm" conditions are regarded as the fatal step resulting in most mortality. Hemoperfusion is widely used to remove cytokines from the blood of severely ill patients to prevent uncontrolled inflammation induced by a cytokine storm. This article discoveres, for the first time, that 2D Ti3 C2 Tx MXene sheet demonstrates an ultrahigh removal capability for typical cytokine interleukin-6. In particular, MXene shows a 13.4 times higher removal efficiency over traditional activated carbon absorbents. Molecular-level investigations reveal that MXene exhibits a strong chemisorption mechanism for immobilizing cytokine interleukin-6 molecules, which is different from activated carbon absorbents. MXene sheet also demonstrates excellent blood compatibility without any deleterious side influence on the composition of human blood. This work can open a new avenue to use MXene sheets as an ultraefficient hemoperfusion absorbent to eliminate the cytokine storm syndrome in treatment of severe COVID-19 patients.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Hemoperfusion/methods , Nanostructures/administration & dosage , SARS-CoV-2/immunology , Titanium/administration & dosage , Adsorption , COVID-19/transmission , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/virology , Humans , Interleukin-6/immunology , Nanostructures/chemistry , SARS-CoV-2/isolation & purification , Titanium/chemistry
2.
ACS Appl Bio Mater ; 4(12): 8110-8128, 2021 12 20.
Article in English | MEDLINE | ID: covidwho-1597218

ABSTRACT

The design of advanced nanobiomaterials to improve analytical accuracy and therapeutic efficacy has become an important prerequisite for the development of innovative nanomedicines. Recently, phospholipid nanobiomaterials including 2-methacryloyloxyethyl phosphorylcholine (MPC) have attracted great attention with remarkable characteristics such as resistance to nonspecific protein adsorption and cell adhesion for various biomedical applications. Despite many recent reports, there is a lack of comprehensive review on the phospholipid nanobiomaterials from synthesis to diagnostic and therapeutic applications. Here, we review the synthesis and characterization of phospholipid nanobiomaterials focusing on MPC polymers and highlight their attractive potentials for applications in micro/nanofabricated fluidic devices, biosensors, lab-on-a-chip, drug delivery systems (DDSs), COVID-19 potential usages for early diagnosis and even treatment, and artificial extracellular matrix scaffolds for cellular engineering.


Subject(s)
Biocompatible Materials/chemistry , Drug Carriers/chemistry , Lab-On-A-Chip Devices , Nanostructures/chemistry , Phospholipids/chemistry , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Humans , Microscopy, Confocal , SARS-CoV-2/isolation & purification
3.
Sci Rep ; 11(1): 17263, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1550348

ABSTRACT

Dexamethasone (Dex) is a highly insoluble front-line drug used in cancer therapy. Data from clinical trials indicates that the pharmacokinetics of Dex vary considerably between patients and prolonging drug exposure rather than increasing absolute dose may improve efficacy. Non-toxic, fully biodegradable Dex loaded nanovectors (NV) were formulated, via simple direct hydration within 10 min, as a vehicle to extend exposure and distribution in vivo. Dex-NV were just as effective as the free drug against primary human leukemia cells in vitro and in vivo. Importantly, high levels of DMSO solvent were not required in the NV formulations. Broad distribution of NV was seen rapidly following inoculation into mice. NV accumulated in major organs, including bone marrow and brain, known sanctuary sites for ALL. The study describes a non-toxic, more easily scalable system for improving Dex solubility for use in cancer and can be applied to other medical conditions associated with inflammation.


Subject(s)
Dexamethasone/administration & dosage , Drug Delivery Systems/methods , Nanostructures/chemistry , Polymers/chemistry , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Xenograft Model Antitumor Assays/methods , Animals , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/chemistry , Antineoplastic Agents, Hormonal/pharmacokinetics , Child , Dexamethasone/chemistry , Dexamethasone/pharmacokinetics , Drug Liberation , Humans , Kaplan-Meier Estimate , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Treatment Outcome , Tumor Cells, Cultured , Young Adult
4.
J Mater Chem B ; 9(42): 8851-8861, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1526111

ABSTRACT

Nanomaterial-based optical techniques for biomarker detection have garnered tremendous attention from the nanofabrication community due to their high precision and enhanced limit of detection (LoD) features. These nanomaterials are highly responsive to local refractive index (RI) fluctuations, and their RI unit sensitivity can be tuned by varying the chemical composition, geometry, and dimensions of the utilized nanostructures. To improve the sensitivity and LoD values of these nanomaterials, it is common to increase both dimensions and aspect ratios of the fabricated nanostructures. However, limited by the complexity, prolonged duration, and elevated costs of the available nanofabrication techniques, mass production of these nanostructures remains challenging. To address not only high accuracy, but also speed and production effectiveness in these nanostructures' fabrication, our work reports, for the first time, a fast, high-throughput, and cost-effective nanofabrication protocol for routine manufacturing of polymer-based nanostructures with high sensitivity and calculated LoD in the pM range by utilizing anodized aluminum oxide (AAO) membranes as templates. Specifically, our developed platform consists of arrays of nearly uniform polystyrene nanopillars with an average diameter of ∼185 nm and aspect ratio of ∼11. We demonstrate that these nanostructures can be produced at a high speed and a notably low price, and that they can be efficiently applied for biosensing purposes after being coated with aluminum-doped silver (Ag/Al) thin films. Our platform successfully detected very low concentrations of human C-reactive protein (hCRP) and SARS-CoV-2 spike protein biomarkers in human plasma samples with LoDs of 11 and 5 pM, respectively. These results open new opportunities for day-to-day fabrication of high aspect ratio arrays of nanopillars that can be used as a base for nanoplasmonic sensors with competitive LoD values. This, in turn, contributes to the development of point-of-care devices and further improvement of the existing nanofabrication techniques, thereby enriching the fields of pharmacology, clinical analysis, and diagnostics.


Subject(s)
Aluminum Oxide/chemistry , Biomarkers/blood , High-Throughput Screening Assays/methods , Nanostructures/chemistry , Silver/chemistry , Biosensing Techniques , C-Reactive Protein/analysis , COVID-19/diagnosis , COVID-19/virology , Dimethylpolysiloxanes/chemistry , Humans , Limit of Detection , Point-of-Care Systems , Polystyrenes/chemistry , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/blood
5.
ACS Appl Bio Mater ; 4(11): 7921-7931, 2021 11 15.
Article in English | MEDLINE | ID: covidwho-1500415

ABSTRACT

The advent of COVID-19 pandemic has made it necessary to wear masks across populations. While the N95 mask offers great performance against airborne infections, its multilayered sealed design makes it difficult to breathe for a longer duration of use. The option of using highly breathable cloth or silk masks especially for a large populace is fraught with the danger of infection. As a normal cloth or silk mask absorbs airborne liquid, it can be a source of plausible infection. We demonstrate the chemical modification of one such mask, Eri silk, to make it hydrophobic (contact angle of water is 143.7°), which reduces the liquid absorption capacity without reducing the breathability of the mask significantly. The breathability reduces only 22% for hydrophobic Eri silk compared to the pristine Eri silk, whereas N95 shows a 59% reduction of breathability. The modified hydrophobic silk can repel the incoming aqueous liquid droplets without wetting the surface. The results indicate that a multilayered modified silk mask to make it hydrophobic can be an affordable and breathable alternative to the N95 mask.


Subject(s)
COVID-19/prevention & control , Masks , Nanostructures/chemistry , Breath Tests , COVID-19/virology , Humans , Hydrophobic and Hydrophilic Interactions , Porosity , Respiratory Protective Devices/virology , SARS-CoV-2/isolation & purification , Silanes/chemistry , Silk/chemistry
6.
Nanotechnology ; 33(6)2021 Nov 19.
Article in English | MEDLINE | ID: covidwho-1493587

ABSTRACT

Wearing a face mask has become a necessity following the outbreak of the coronavirus (COVID-19) disease, where its effectiveness in containing the pandemic has been confirmed. Nevertheless, the pandemic has revealed major deficiencies in the ability to manufacture and ramp up worldwide production of efficient surgical-grade face masks. As a result, many researchers have focused their efforts on the development of low cost, smart and effective face covers. In this article, following a short introduction concerning face mask requirements, the different nanotechnology-enabled techniques for achieving better protection against the SARS-CoV-2 virus are reviewed, including the development of nanoporous and nanofibrous membranes in addition to triboelectric nanogenerators based masks, which can filter the virus using various mechanisms such as straining, electrostatic attraction and electrocution. The development of nanomaterials-based mask coatings to achieve virus repellent and sterilizing capabilities, including antiviral, hydrophobic and photothermal features are also discussed. Finally, the usability of nanotechnology-enabled face masks is discussed and compared with that of current commercial-grade N95 masks. To conclude, we highlight the challenges associated with the quick transfer of nanomaterials-enabled face masks and provide an overall outlook of the importance of nanotechnology in counteracting the COVID-19 and future pandemics.


Subject(s)
COVID-19/prevention & control , Masks , Nanotechnology , SARS-CoV-2/isolation & purification , COVID-19/epidemiology , COVID-19/transmission , Filtration , Humans , Hydrophobic and Hydrophilic Interactions , Nanofibers/chemistry , Nanostructures/chemistry , User-Centered Design
7.
J Mater Chem B ; 9(39): 8185-8201, 2021 10 13.
Article in English | MEDLINE | ID: covidwho-1414146

ABSTRACT

During the global outbreak of coronavirus disease 2019 (COVID-19), a hyperinflammatory state called the cytokine storm was recognized as a major contributor to multiple organ failure and mortality. However, to date, the diagnosis and treatment of the cytokine storm remain major challenges for the clinical prognosis of COVID-19. In this review, we outline various nanomaterial-based strategies for preventing the COVID-19 cytokine storm. We highlight the contribution of nanomaterials to directly inhibit cytokine release. We then discuss how nanomaterials can be used to deliver anti-inflammatory drugs to calm the cytokine storm. Nanomaterials also play crucial roles in diagnostics. Nanomaterial-based biosensors with improved sensitivity and specificity can be used to detect cytokines. In summary, emerging nanomaterials offer platforms and tools for the detection and treatment of the COVID-19 cytokine storm and future pandemic.


Subject(s)
COVID-19/complications , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Nanostructures/chemistry , Nanostructures/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacology , Humans
8.
Int J Nanomedicine ; 16: 4813-4830, 2021.
Article in English | MEDLINE | ID: covidwho-1406766

ABSTRACT

Human coronaviruses present a substantial global disease burden, causing damage to populations' health, economy, and social well-being. Glycans are one of the main structural components of all microbes and organismic structures, including viruses-playing multiple essential roles in virus infection and immunity. Studying and understanding virus glycans at the nanoscale provide new insights into the diagnosis and treatment of viruses. Glycan nanostructures are considered potential targets for molecular diagnosis, antiviral therapeutics, and the development of vaccines. This review article describes glycan nanostructures (eg, glycoproteins and glycolipids) that exist in cells, subcellular structures, and microbes. We detail the structure, characterization, synthesis, and functions of virus glycans. Furthermore, we describe the glycan nanostructures of different human coronaviruses, such as human coronavirus 229E (HCoV-229E), human coronavirus OC43 (HCoV-OC43), severe acute respiratory syndrome-associated coronavirus (SARS-CoV), human coronavirus NL63 (HCoV-NL63), human coronavirus HKU1 (HCoV-HKU1), the Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and how glycan nanotechnology can be useful to prevent and combat human coronaviruses infections, along with possibilities that are not yet explored.


Subject(s)
Betacoronavirus/chemistry , Nanostructures/analysis , Nanostructures/chemistry , Polysaccharides/analysis , Polysaccharides/chemistry , Humans
9.
Molecules ; 26(2)2021 Jan 15.
Article in English | MEDLINE | ID: covidwho-1389464

ABSTRACT

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.


Subject(s)
Anti-Infective Agents/pharmacology , Antiviral Agents/pharmacology , Peptides/chemistry , Peptides/pharmacology , Peptides/therapeutic use , Amino Acids/chemistry , Anti-Infective Agents/chemistry , Antiviral Agents/chemistry , COVID-19/drug therapy , Computer Simulation , Cosmeceuticals/chemistry , Cosmeceuticals/therapeutic use , Dietary Supplements , Gene Transfer Techniques , Humans , Lactoferrin/chemistry , Lipid Bilayers , Nanostructures/administration & dosage , Nanostructures/chemistry , Peptides/administration & dosage , Stem Cells , Vaccines, Subunit/chemistry , Vaccines, Subunit/pharmacology
10.
Anal Bioanal Chem ; 413(18): 4635-4644, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1384376

ABSTRACT

Pd-Ir nanocubes are promising peroxidase-mimicking nanozymes for immunoassays, enabled by their excellent stability, relatively high catalytic activity, and reproducible performance. A key step involved in the preparation of Pd-Ir nanocubes is the synthesis of Pd nanocubes. However, the traditional method to synthesize Pd nanocubes requires sophisticated and expensive equipment to precisely control the reaction temperature and highly skilled technicians to achieve satisfactory and reproducible product yields. Herein, we report a simple, cost-effective, high-yield (> 99%) and one-pot strategy to synthesize Pd nanocubes with sizes of 7, 18, and 51 nm for the preparation of Pd-Ir nanocubes. The resulting 18 nm Pd-Ir nanocubes display three orders of magnitude higher peroxidase activity compared to horseradish peroxidase, leading to a significantly increased detection sensitivity when applied in the immunoassay of nucleocapsid protein from SARS-CoV-2. Due to the simplicity in both material synthesis and assaying procedures and the excellent detection sensitivity, our method should allow for the generalized application of Pd-Ir nanocube-based immunoassays for the diagnosis of human diseases.


Subject(s)
COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/chemistry , Immunoassay/methods , Iridium/chemistry , Palladium/chemistry , SARS-CoV-2 , Antibodies, Viral , Cost-Benefit Analysis , Humans , Immunoassay/economics , Molecular Structure , Nanostructures/chemistry , Nanostructures/economics , Phosphoproteins/chemistry
11.
ACS Appl Mater Interfaces ; 12(50): 55614-55623, 2020 Dec 16.
Article in English | MEDLINE | ID: covidwho-1387129

ABSTRACT

Multiplexed detection of viral nucleic acids is important for rapid screening of viral infection. In this study, we present a molybdenum disulfide (MoS2) nanosheet-modified dendrimer droplet microarray (DMA) for rapid and sensitive detection of retroviral nucleic acids of human immunodeficiency virus-1 (HIV-1) and human immunodeficiency virus-2 (HIV-2) simultaneously. The DMA platform was fabricated by omniphobic-omniphilic patterning on a surface-grafted dendrimer substrate. Functionalized MoS2 nanosheets modified with fluorescent dye-labeled oligomer probes were prepatterned on positively charged amino-modified omniphilic spots to form a fluorescence resonance energy transfer (FRET) sensing microarray. With the formation of separated microdroplets of sample on the hydrophobic-hydrophilic micropattern, prepatterned oligomer probes specifically hybridized with the target HIV genes and detached from the MoS2 nanosheet surface due to weakening of the adsorption force, leading to fluorescence signal recovery. As a proof of concept, we used this microarray with a small sample size (<150 nL) for simultaneous detection of HIV-1 and HIV-2 nucleic acids with a limit of detection (LOD) of 50 pM. The multiplex detection capability was further demonstrated for simultaneous detection of five viral genes (HIV-1, HIV-2, ORFlab, and N genes of SARS-COV-2 and M gene of Influenza A). This work demonstrated the potential of this novel MoS2-DMA FRET sensing platform for high-throughput multiplexed viral nucleic acid screening.


Subject(s)
Biosensing Techniques , COVID-19/diagnosis , HIV Infections/diagnosis , HIV/isolation & purification , COVID-19/genetics , COVID-19/virology , Disulfides/chemistry , Fluorescence , Fluorescence Resonance Energy Transfer , HIV/pathogenicity , HIV Infections/genetics , HIV Infections/virology , Humans , Molybdenum/chemistry , Nanostructures/chemistry , Nucleic Acids/genetics , Nucleic Acids/isolation & purification , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity
12.
Adv Mater ; 33(40): e2102528, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1358054

ABSTRACT

Dendritic cell (DC) vaccines are used for cancer and infectious diseases, albeit with limited efficacy. Modulating the formation of DC-T-cell synapses may greatly increase their efficacy. The effects of graphene oxide (GO) nanosheets on DCs and DC-T-cell synapse formation are evaluated. In particular, size-dependent interactions are observed between GO nanosheets and DCs. GOs with diameters of >1 µm (L-GOs) demonstrate strong adherence to the DC surface, inducing cytoskeletal reorganization via the RhoA-ROCK-MLC pathway, while relatively small GOs (≈500 nm) are predominantly internalized by DCs. Furthermore, L-GO treatment enhances DC-T-cell synapse formation via cytoskeleton-dependent membrane positioning of integrin ICAM-1. L-GO acts as a "nanozipper," facilitating the aggregation of DC-T-cell clusters to produce a stable microenvironment for T cell activation. Importantly, L-GO-adjuvanted DCs promote robust cytotoxic T cell immune responses against SARS-CoV-2 spike 1, leading to >99.7% viral RNA clearance in mice infected with a clinically isolated SARS-CoV-2 strain. These findings highlight the potential value of nanomaterials as DC vaccine adjuvants for modulating DC-T-cell synapse formation and provide a basis for the development of effective COVID-19 vaccines.


Subject(s)
Adjuvants, Immunologic/therapeutic use , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Dendritic Cells/immunology , Graphite/therapeutic use , Nanostructures/therapeutic use , Adjuvants, Immunologic/chemistry , Animals , COVID-19/immunology , COVID-19 Vaccines/immunology , Dendritic Cells/drug effects , Graphite/chemistry , Humans , Mice , Nanostructures/chemistry , SARS-CoV-2/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology
13.
J Mater Chem B ; 9(36): 7328-7346, 2021 09 22.
Article in English | MEDLINE | ID: covidwho-1351983

ABSTRACT

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) caused the COVID-19 pandemic. According to the World Health Organization, this pandemic continues to be a serious threat to public health due to the worldwide spread of variants and their higher rate of transmissibility. A range of measures are necessary to slow the pandemic and save lives, which include constant evaluation and the careful adjustment of public-health responses augmented by medical treatments, vaccines and protective gear. It is hypothesized that nanostructured particulates underpinned by nanoscience and quantum science yield high-performing antiviral strategies, which can be applied in preventive, diagnostic, and therapeutic applications such as face masks, respirators, COVID test kits, vaccines, and drugs. This review is aimed at providing comprehensive and cohesive perspectives on various nanostructures that are suited to intensifying and amplifying the effectiveness of antiviral strategies. Growing scientific literature over the past eighteen months indicates that quantum dots, iron oxide, silicon oxide, polymeric and metallic nanoparticles have been employed in COVID-19 diagnostic assays, vaccines, and personal protective equipment (PPE). Quantum dots have displayed their suitability as more sensitive imaging probes in diagnostics and prognostics, and as controlled drug-release carriers that target the virus. Nanoscience and quantum science have assisted the design of advanced vaccine delivery since nanostructured materials are suited for antigen delivery, as mimics of viral structures and as adjuvants. Furthermore, the quantum science- and nanoscience-supported tailored functionalization of nanostructured materials offers insight and pathways to deal with future pandemics. This review seeks to illustrate several examples, and to explain the underpinning quantum science and nanoscience phenomena, which include wave functions, electrostatic interactions, van der Waals forces, thermal and electrodynamic fluctuations, dispersion forces, local field-enhancement effects, and the generation of reactive oxygen species (ROS). This review discusses how nanostructured materials are helpful in the detection, prevention, and treatment of the SARS-CoV-2 infection, other known viral infection diseases, and future pandemics.


Subject(s)
Antiviral Agents/chemistry , Nanostructures/chemistry , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Disinfection/methods , Drug Carriers/chemistry , Humans , Personal Protective Equipment , Reactive Oxygen Species/chemistry , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification , Virus Diseases/drug therapy , Virus Diseases/virology
14.
ACS Appl Bio Mater ; 4(7): 5471-5484, 2021 07 19.
Article in English | MEDLINE | ID: covidwho-1337090

ABSTRACT

Centers for Disease Control and Prevention (CDC) warns the use of one-way valves or vents in face masks for potential threat of spreading COVID-19 through expelled respiratory droplets. Here, we have developed a nanoceutical cotton fabric duly sensitized with non-toxic zinc oxide nanomaterial for potential use as a membrane filter in the one-way valve for the ease of breathing without the threat of COVID-19 spreading. A detailed computational study revealed that zinc oxide nanoflowers (ZnO NFs) with almost two-dimensional petals trap SARS-CoV-2 spike proteins, responsible to attach to ACE-2 receptors in human lung epithelial cells. The study also confirmed significant denaturation of the spike proteins on the ZnO surface, revealing removal of the virus upon efficient trapping. Following the computational study, we have synthesized ZnO NF on a cotton matrix using a hydrothermal-assisted strategy. Electron-microscopic, steady-state, and picosecond-resolved spectroscopic studies confirm attachment of ZnO NF to the cotton (i.e., cellulose) matrix at the atomic level to develop the nanoceutical fabric. A detailed antimicrobial assay using Pseudomonas aeruginosa bacteria (model SARS-CoV-2 mimic) reveals excellent antimicrobial efficiency of the developed nanoceutical fabric. To our understanding, the nanoceutical fabric used in the one-way valve of a face mask would be the choice to assure breathing comfort along with source control of COVID-19 infection. The developed nanosensitized cloth can also be used as an antibacterial/anti CoV-2 washable dress material in general.


Subject(s)
Anti-Infective Agents/chemistry , COVID-19/prevention & control , Nanostructures/chemistry , Anti-Infective Agents/metabolism , Anti-Infective Agents/pharmacology , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , COVID-19/virology , Cotton Fiber/analysis , Humans , Masks , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/metabolism , Recycling , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Zinc Oxide/chemistry
15.
Small Methods ; 5(9): e2100402, 2021 09.
Article in English | MEDLINE | ID: covidwho-1330355

ABSTRACT

In recent years, the main quest of science has been the pioneering of the groundbreaking biomedical strategies needed for achieving a personalized medicine. Ribonucleic acids (RNAs) are outstanding bioactive macromolecules identified as pivotal actors in regulating a wide range of biochemical pathways. The ability to intimately control the cell fate and tissue activities makes RNA-based drugs the most fascinating family of bioactive agents. However, achieving a widespread application of RNA therapeutics in humans is still a challenging feat, due to both the instability of naked RNA and the presence of biological barriers aimed at hindering the entrance of RNA into cells. Recently, material scientists' enormous efforts have led to the development of various classes of nanostructured carriers customized to overcome these limitations. This work systematically reviews the current advances in developing the next generation of drugs based on nanotechnology-assisted RNA delivery. The features of the most used RNA molecules are presented, together with the development strategies and properties of nanostructured vehicles. Also provided is an in-depth overview of various therapeutic applications of the presented systems, including coronavirus disease vaccines and the newest trends in the field. Lastly, emerging challenges and future perspectives for nanotechnology-mediated RNA therapies are discussed.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/therapy , Drug Delivery Systems/methods , Nanostructures/administration & dosage , Nanotechnology/methods , RNA/administration & dosage , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , Humans , Nanostructures/chemistry , RNA/chemistry , SARS-CoV-2/isolation & purification
16.
Adv Sci (Weinh) ; 8(18): e2101155, 2021 09.
Article in English | MEDLINE | ID: covidwho-1316191

ABSTRACT

Accessible and adaptable nucleic acid diagnostics remains a critical challenge in managing the evolving COVID-19 pandemic. Here, an integrated molecular nanotechnology that enables direct and programmable detection of SARS-CoV-2 RNA targets in native patient specimens is reported. Termed synergistic coupling of responsive equilibrium in enzymatic network (SCREEN), the technology leverages tunable, catalytic molecular nanostructures to establish an interconnected, collaborative architecture. SCREEN mimics the extraordinary organization and functionality of cellular signaling cascades. Through programmable enzyme-DNA nanostructures, SCREEN activates upon interaction with different RNA targets to initiate multi-enzyme catalysis; through system-wide favorable equilibrium shifting, SCREEN directly transduces a single target binding into an amplified electrical signal. To establish collaborative equilibrium coupling in the architecture, a computational model that simulates all reactions to predict overall performance and optimize assay configuration is developed. The developed platform achieves direct and sensitive RNA detection (approaching single-copy detection), fast response (assay reaction is completed within 30 min at room temperature), and robust programmability (across different genetic loci of SARS-CoV-2). When clinically evaluated, the technology demonstrates robust and direct detection in clinical swab lysates to accurately diagnose COVID-19 patients.


Subject(s)
COVID-19/virology , DNA, Catalytic/genetics , Nanostructures/chemistry , SARS-CoV-2/genetics , Humans , Limit of Detection , Molecular Diagnostic Techniques/methods , Nanotechnology/methods , Pandemics/prevention & control , RNA, Viral/genetics , Specimen Handling/methods
17.
Proc Natl Acad Sci U S A ; 118(29)2021 07 20.
Article in English | MEDLINE | ID: covidwho-1307382

ABSTRACT

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.


Subject(s)
COVID-19/prevention & control , Nanostructures/administration & dosage , SARS-CoV-2/drug effects , Adhesives/administration & dosage , Adhesives/chemistry , Adhesives/pharmacokinetics , Administration, Inhalation , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cryoprotective Agents/chemistry , Drug Storage , Epithelial Cells/metabolism , Excipients/administration & dosage , Excipients/chemistry , Excipients/pharmacokinetics , HEK293 Cells , Humans , Hyaluronic Acid/administration & dosage , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacokinetics , Lung/drug effects , Lung/metabolism , Lung/virology , Mice , Mice, Transgenic , Nanostructures/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Virus Attachment/drug effects
18.
J Mater Chem B ; 9(30): 5967-5981, 2021 08 04.
Article in English | MEDLINE | ID: covidwho-1307349

ABSTRACT

The infamous COVID-19 outbreak has left a crippling impact on the economy, healthcare infrastructure, and lives of the general working class, with all the scientists determined to find suitable and efficient diagnostic techniques and therapies to contain its ramifications. This article presents the complete outline of the diagnostic platforms developed using nanoparticles in the detection of SARS-CoV-2, delineating the direct and indirect use of nanomaterials in COVID-19 diagnosis. The properties of nanostructured materials and their relevance in the development of novel point-of-care diagnostic approaches for COVID-19 are highlighted. More importantly, the advantages of nanotechnologies over conventional reverse transcriptase-polymerase chain reaction technique and few other methods used in the detection of SARS-CoV-2 along with the viewpoints are discussed. Also, the future perspectives highlighting the commercial aspects of the nanotechnology-based diagnostic tools developed to combat the COVID-19 pandemic are presented.


Subject(s)
COVID-19/diagnosis , Nanostructures/chemistry , Point-of-Care Testing , Antibodies, Viral/analysis , Antibodies, Viral/chemistry , Biosensing Techniques/methods , COVID-19/virology , Colorimetry , Humans , Nucleic Acid Amplification Techniques , RNA, Viral/analysis , RNA, Viral/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
19.
Molecules ; 26(12)2021 Jun 10.
Article in English | MEDLINE | ID: covidwho-1282535

ABSTRACT

Peptides and their synthetic analogs are a class of molecules with enormous relevance as therapeutics for their ability to interact with biomacromolecules like nucleic acids and proteins, potentially interfering with biological pathways often involved in the onset and progression of pathologies of high social impact. Nucleobase-bearing peptides (nucleopeptides) and pseudopeptides (PNAs) offer further interesting possibilities related to their nucleobase-decorated nature for diagnostic and therapeutic applications, thanks to their reported ability to target complementary DNA and RNA strands. In addition, these chimeric compounds are endowed with intriguing self-assembling properties, which are at the heart of their investigation as self-replicating materials in prebiotic chemistry, as well as their application as constituents of innovative drug delivery systems and, more generally, as novel nanomaterials to be employed in biomedicine. Herein we describe the properties of nucleopeptides, PNAs and related supramolecular systems, and summarize some of the most relevant applications of these systems.


Subject(s)
Nanostructures/chemistry , Peptide Nucleic Acids/chemistry , Peptides/chemistry , Animals , DNA/chemistry , Humans , Prebiotics , RNA/chemistry
20.
Nat Struct Mol Biol ; 28(7): 573-582, 2021 07.
Article in English | MEDLINE | ID: covidwho-1279891

ABSTRACT

SARS-CoV-2 ORF3a is a putative viral ion channel implicated in autophagy inhibition, inflammasome activation and apoptosis. 3a protein and anti-3a antibodies are found in infected patient tissues and plasma. Deletion of 3a in SARS-CoV-1 reduces viral titer and morbidity in mice, suggesting it could be an effective target for vaccines or therapeutics. Here, we present structures of SARS-CoV-2 3a determined by cryo-EM to 2.1-Å resolution. 3a adopts a new fold with a polar cavity that opens to the cytosol and membrane through separate water- and lipid-filled openings. Hydrophilic grooves along outer helices could form ion-conduction paths. Using electrophysiology and fluorescent ion imaging of 3a-reconstituted liposomes, we observe Ca2+-permeable, nonselective cation channel activity, identify mutations that alter ion permeability and discover polycationic inhibitors of 3a activity. 3a-like proteins are found across coronavirus lineages that infect bats and humans, suggesting that 3a-targeted approaches could treat COVID-19 and other coronavirus diseases.


Subject(s)
Cryoelectron Microscopy , Nanostructures , SARS-CoV-2 , Viroporin Proteins/chemistry , Viroporin Proteins/ultrastructure , Animals , Calcium/metabolism , Chiroptera/virology , Coronaviridae , Electrophysiology , Fluorescence , Humans , Ion Transport , Liposomes , Models, Molecular , Nanostructures/chemistry , Nanostructures/ultrastructure , Open Reading Frames , Optical Imaging , Reproducibility of Results , SARS-CoV-2/chemistry , SARS-CoV-2/ultrastructure , Sequence Homology , Viral Proteins/chemistry , Viral Proteins/ultrastructure , Viroporin Proteins/antagonists & inhibitors
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