key: cord-1049793-8thmjvlt
authors: Tavakol, Shima; Zahmatkeshan, Masoumeh; Mohammadinejad, Mohammad R.; Mehrzadi, Saeed; Joghataei, Mohammad T.; Alavijeh, Mo S.; Seifalian, Alexander
title: The role of Nanotechnology in current COVID-19 outbreak
date: 2021-04-15
journal: Heliyon
DOI: 10.1016/j.heliyon.2021.e06841
sha: 5dd57ee04e114159a4e73a03b1f0630eb2c2d509
doc_id: 1049793
cord_uid: 8thmjvlt

COVID-19 has recently become one of the most challenging pandemics of the last century with deadly outcomes and a high rate of reproduction number. It emphasizes the critical need for the designing of efficient vaccines to prevent virus infection, early and fast diagnosis by the high sensitivity and selectivity diagnostic kits, and effective antiviral and protective therapeutics to decline and eliminate the viral load and side effects derived from tissue damages. Therefore, non-toxic antiviral nanoparticles (NPs) have been under development for clinical application to prevent and treat COVID-19. NPs showed great promise to provide nano vaccines against viral infections. Here, we discuss the potentials of NPs that may be applied as a drug itself or as a platform for the aim of drug and vaccine repurposing and development. Meanwhile, the advanced strategies based on NPs to detect viruses will be described with the goal of encouraging scientists to design effective and cost-benefit nanoplatforms for prevention, diagnosis, and treatment.

COVID-19 is caused by the SARS-CoV-2 virus and it has recently become one of the most challenging pandemics of the last century with deadly outcomes and a high rate of reproduction number and transmission. Since late 2002, coronaviruses have become a serious epidemic problem with severe acute respiratory syndrome coronavirus (SARS) and then with the onset of the Middle East respiratory syndrome (MERS) in late 2012. The enveloped ssRNA + virus with an average particle size of 120-160 nm belongs to the subfamily, family, order, and the realm of Orthocoronavirinae, Coronaviridae, Nidovirales, and Riboviria, respectively 1 . Coronaviruses encode some structural and non-structural proteins that might be considered as an anti-viral target, including phosphorylated nucleocapsid, envelope, membrane glycoproteins, spike, helicase, papain-like protease and 3-chymotrypsin-like protease 2 .

Although several of clinical trials are underway, currently, there is no clinically effective protective vaccine or therapeutic drug for COVID-19 patients in the world. Due to the urgent need for the treatment of COVID-19 patients and the desperation of uncertainly of any new vaccine, drug repurposing has been considered as a promising strategy. Therefore, the crucial step in drug repurposing is to have a thorough and accurate understanding and knowledge of structural differences of the coronaviruses and RNA (Ribonucleic acid) viruses and their involved receptors in a host.

Both SARS and COVID-19 were started from China during the spring festival with the same animal source, bat, and eventually pangolin in COVID-19 3 . To the best of our knowledge, the coronavirus responsible for SARS and COVID-19 attached to the receptorbinding site of angiotensin-converting enzyme 2 (ACE2). However, MERS was started from Saudi Arabia with the animal source of camel and dipeptidyl peptidase-4 (DPP4) receptor involvement. The age of involvement in MERS and COVID-19 is middle age and occurs mostly in patients with the underlying disease for 2-14 days post-exposure, unlike the SARS in young individuals.

As a view of clinical features, these viruses share some similarities and differences. They all appear to have common clinical symptoms such as fever, cough, and general symptoms of the common cold. Pathologically, ACE2 a cell surface receptor in human is the main receptor of the SARS-CoV-2 virus. It is over-expressed in the lung, heart, kidney, testis, intestine, and brain. Therefore, we expect these organs to experience cell and tissue damages in part due to cytokine storm. However, CD147 (Basigin) as an extracellular matrix metalloproteinase inducer is considered as the other receptor for SARS-CoV-2 on the surface of lots of cells, J o u r n a l P r e -p r o o f including epithelial cells, endothelial cells, leukocytes, red blood cells, etc. It is the receptors of plasmodium falciparum on red blood cells, and also it has rules in spermatogenesis, the responsiveness of lymphocytes, etc. 2 . However, the disruption of the CD147-C-type lectin leads to the induction of prostate cancer 4 . The point is related to the eventual influence of prostate tissue by SARS-CoV-2 through the involvement of CD-147. Clinically, MERS and COVID-19 cause higher cardiovascular problems than the SARS, while SARS and COVID-19 patients more frequently than MERS experienced renal and neurological problems.

The mechanism underlying the COVID-19 disease is in part related to the decline of ACE2 (angiotensin-converting enzyme 2) owing to the entrance of the virus by its spike glycoprotein resulting in spike cleavage by transmembrane protease TMPRSS2. It triggers a cascade that leads to inflammation, TNF-α production, and tissue damage through the Cterminal cleavage of ACE2 by the TNF-alpha-converting enzyme (TACE). The sodiumdependent neutral amino acid transporter (SLC6A19 or B0AT1) occupies the C-terminal cleavage site and inhibits the effects of TACE on ACE2. The inhibition of TACE, reninangiotensin pathway, C-terminal cleavage of ACE2, TNF-α, and inflammatory inhibitors will decrease the level of virus infection and tissue damage. As depicted in Fig. 2 , a virus is entered by binding to the ACE2 receptor on the cell surface of target cells and infects host cells.

However, chloroquine has the potential to interfere at different points of this cycle. Furthermore, chloroquine has a possible inhibitory effect on the MAPK kinase activity and hence a downregulation of certain proinflammatory responses.

From the other side, the interaction of the virus by CD147 will cause other parts of pathogenesis in patients 5 . However, one of the most crucial pathogenesis mechanisms of SARS-CoV and MERS-CoV is through delay interferon, TNF-α, and pro-inflammatory responses that lead to the decrement of innate immunity in the host 6 .

In the present paper, we discuss the diagnostic and therapeutic strategies for the other viruses which have similar mechanisms of action with SARS-CoV-2. The aim was to repurpose some strategies to diagnosis and cure the COVID-19 based on successfulness in similar diseases aiming to reduce the time and cost of diagnosis and treatment.

To design and evaluate a successful drug and vaccine repurposing, it is necessary to know how much SARS-CoV-2 is close to the MERS-CoV and SARS-CoV as a genotype and J o u r n a l P r e -p r o o f structure (Table 1) . Nucleotide sequence identity among the human coronaviruses, SARS-CoV, and SARS-CoV-2, are varying from 99.99-79.7% and 82% in COVID-19 patients. The sequence homology of SARS-CoV and MERS-CoV with SARS-CoV-2 are 70-77.5% and 50%, respectively 7, 8 . The proteins of the envelope, membrane, nucleocapsid, S1, and S2 have 95-96, 91, 89.6-94, 70 and 99% similarity in SARS-CoV and SARS-CoV-2, respectively 7, 9, 10 .

Noteworthy, the spike of MERS-CoV and SARS-CoV-2 just have a 31.9% amino acid identity that makes it unfavourable for drug repurposing in COVID-19 therapy. Furthermore, receptorbinding domain (RBD) of spike and ORF3b, ORF8 in SARS-CoV-2, just have 40, 32 and 40% amino acid identity with SARS-CoV 10, 11 . Moreover, SARS-CoV-2 has some mutations such as replacing serine instead of glycine and proline instead of isoleucine in the position of 723 and 1010 of ORF1ab compared to SARS-CoV, respectively 12 . ORF1ab is involved in the synthesis of papain-like protease: nsp3, chymotrypsin-like: nsp5, RNA dependent RNA polymerase: nsp12 (96%), helicase (100%): nsp13 10 . The function of every non-structural protein (nsp) and its sequence identity with SARS-CoV has been mentioned in Table 1 . Based on these pieces of information, for the drug repurposing, we can select the drugs and vaccines that share antiviral efficacy among the SARS and COVID-19 by the targeting of the envelope, membrane, nucleocapsid, S2 spike, RdRp, helicase, etc. 10 (Table 1) .

Zhou et al. 9 found 47 human proteins in the HCoV-host interactome and as a targeting biomolecules for targeting in drug development such as STAT3, BCL2, SMAD3, PARP1, GSK3B, etc. They found several HCoV-host interactions by network proximity analyses in a human interactome and suggested repurposing of some drugs for COVID-19 treatment 9 . The targeting of these proteins by the pre-exist drugs may overcome the obstacles from the COVID-19. However, the encapsulation and decoration of drugs into/on nanoparticles will enhance their efficacy.

The first stage of diagnosis in COVID-19 patients is based on a traveling and communication history of patients. Then Chest X-Ray and CT are recommended to detect ground-glass opacity and patchy bilateral shadows in the lungs. Other analyses on blood serum are differential CBC, CRP, LDH, AST/AL, procalcitonin, troponin I. Lymphopenia in patients indicated a bad prognosis of the disease. To detect the virus in specimens, Real-time RT-PCR is recommended. However, the diagnostic kit based on the RT-PCR technique has varied negative results. The PCR positive results are valuable, and the negative results do not reject J o u r n a l P r e -p r o o f the possible diseases. A systematic review indicated that the CT scan is a valuable diagnostic method for the symptomatic and hospitalized patient, however, at the early stage PCR method is recommended 13 . The biodistribution of SARS-CoV-2 in bronchoalveolar lavage fluid, sputum, nasal, fibre-bronchoscope brush biopsy, pharyngeal, stool, blood and urine, and their biodistribution were 93, 72, 63, 46, 32, 29, 1 and 0%, respectively, during three days of hospitalization 14 .

Accurate and early detection plays a critical role in limiting COVID-19 spread and prevents future epidemics. Nanotechnology, based on molecular techniques and specific pathogens targeting, has emerged as a promising strategy in the early and fast COVID-19 detection. In the field of NPs applications for SARS-CoV-2 detection, RNA might be extracted using high-affinity silica-coated iron oxide NPs. Recently 15 has been reviewed diagnostic strategies for SARS-CoV-2, focusing on nanotechnology. Notably, a molecular-based technique to assess the RNA virus has superior sensitivity compared to antibody-based methods and serology. However, a lateral flow antigen detection based on colloidal gold NPs is under investigation 16 and it seems that since virus infection is started from the lung, the rapid scientists developed an RNA stabilization kit that stabilizes RNA of the virus at room temperature to prevent its degradation up to one week storage 19 .

As depicted in table 1, it was shown some protein and structural similarities and differences between SARS-CoV, MERS-CoV and SARS-CoV-2 and then in Table 2 , it was summarized the recent advancements in nanoplatforms for the detection and treatment of SARS-CoV-2 with regards to its similarities and differences with two other sisters. The other Nano platforms for the diagnosis of coronaviruses are polymeric NPs 21 , chaperone-mediated ferritin nanoparticles 22 , Nanobodies 23-27 , Self-Assembling Protein Nanoparticle (SAPN) 28 , an J o u r n a l P r e -p r o o f adenoviral vector encoding Ad5 29 , spike protein nanoparticles 30 , VLPs 31 , AuNPs 32 , AgNPs 33 , Lumazine synthase NPs 34, 35 , Microneedle array (MNA) delivered SARS-CoV-2 S1 subunit vaccines 36 . The based on the structure and protein similarities between SARS-CoV, MERS-CoV and SARS-CoV-2, it may be proposed a diagnostic method with less time and cost to design a new kit.

Nanomedicine, the application of nanomaterials to medicine, is used in vectors, biosensors, drug and gene delivery. Nanotechnology, by taking off its unique physicochemical characteristics, leads to improved therapeutic efficacy through enhanced drug bioavailability, overcome to the low Log P (hydrophobicity or insolubility in water), specific delivery to target sites in cellular and intracellular levels and reduces side effects; it can also overcome the drug resistance, which is beneficial for viral treatment. Nanomaterials that are scientifically engineered are used to help pharmaceutical companies; they help to enhance the effectiveness of therapy and target specific dysfunctional organs or decaying body cells. The emergence of nanomaterials in recent years is swiftly transforming the scientific landscape of fields as diverse as aerospace, military, and medicine. Nanoparticles (NPs) possessing unique physicochemical properties showed virucidal activities 37 . Small size, large surface area, targetability, and stimulus-responsive characteristics, make NPs the effective antiviral agents. NPs such as iron oxide, zinc oxide, silver, carbon-based and AVNP2 are considered as the promising agents to modulate the viral infection process. Metal NPs through their localized surface plasmon resonance (LSPR) effect may act as the theranostic agents for the diagnostic and therapeutic applications 38 42 . It has been shown that nitric oxide (NO) nanoparticles through the supplementation of NO for endothelial cells and also, inhibition of RNA replication by peroxynitrite residue derived from NO prevent SARS-CoV infection and virulence 43 . Nanomaterials such as AuNPs can be used to bind the coronavirus and interrupt its structure through infrared light emission, and then the virus is deactivated by nanomaterials. In addition to the antiviral properties, NPs are determined as promising antiviral drugs carriers. They increase the activity of the drugs and improve their bioavailability. For example, chitosan NPs in the form of an aerosol (Novochizol) encapsulate several drugs and J o u r n a l P r e -p r o o f adhere to epithelial cells and can release the drug up to 3h. Therefore, drug dilution in body fluid does not cause reduced drug effectiveness 19 .

Currently, only a few unspecific anti-coronavirus agents with serious adverse effects are available such as Kaletra (Lopinavir/Ritonavir), hydroxychloroquine, oseltamivir phosphate, Azithromycin, etc. Whereas acute respiratory distress syndrome (ARDS) derived from cytokine release syndrome (CRS), especially interleukin (IL)-6, will worsen the patient's fate.

Therefore, the blocking of IL-6 and its receptor with Siltuximab and Tocilizumab are under clinical trial studies 37 . However, the role of lymphocytic apoptosis is not negligible in viral spreading by macrophages in COVID-19 patients 44 . Although there is no specific antiviral therapeutics for COVID-19, some unspecific medicines cured the patients. Nanostructures enhance the efficacy of these therapeutic agents.

Furthermore, siRNA, microRNA, and shRNA regulating viral gene expression will be developed as novel therapeutic agents against COVID-19 45 . NPs cover the noncoding RNA and protect them from enzymes to improve their functions 46 . Nanodiamond particles functionalized and encapsulated with octadecylamine and dexamethasone show promising results dose dependency on declining of TNF-α, iNOS, and macrophage infiltration in mice 47 .

However, the immunosuppression must be targeted to specific immune cells to not leading to sepsis in patients; extracorporeal perfusion of cytokines at the early stages using mesoporous carbon absorbents and graphene 48 makes enough time to host eliminate SARS-CoV-2 and limits mortality in patients derived from cytokine storm, etc.

Noteworthy, combination therapy seems to combat pandemic diseases. Co-delivery systems facilitate combination strategies 49 . Thus, nanocarriers can be applied for the coencapsulation of the candidate drugs such as Remdesivir and hydroxychloroquine to treat COVID-19.

Some studies demonstrated the applications of NPs against coronavirus. Fortunately, airborne nanomaterials due to a small size and their tuneable physicochemical properties suited to penetrate alveolar epithelial type II cells (AECII) in the deep lung. The nanomaterial may be considered as a favourable candidate to deliver therapeutic agents in COVID-19 patients 37 . 63 . The authors announced that they immediately take this approach to combat coronaviruses 64 . Another strategy is to rapidly eliminate pro-inflammatory cytokines from the bloodstream before the further adverse effect in tissues. It seems that extracorporeal perfusion through graphene and porous carbons is promising to quickly remove the cytokines from the blood circulation 48, 65 .

However, a theranostic platform to detect and treat the virus infection is of interest. In this regards, organic, inorganic and virus-like NPs such as lipid NPs, dendrimer, magnetic and gold NPs have been reported 66 . A clinical trial phase 1 has been recently designed to investigate the J o u r n a l P r e -p r o o f safety and efficiency of aerosol inhalation of the exosomes derived from allogeneic adipose mesenchymal stem cells in patients with severe COVID-19 67 . There are several nanostrategies to combat SARS-CoV-2 by repurposing from pharmaceutics for other diseases with similar symptoms including TNF-α inhibitors and interferon producers. TNF-α is accounted as the one of major cytokines involved in cytokine storm and its inhibition will be promising to decline tissue damage thereof. To this aim, TNF-α-siRNA will be helpful especially when are encapsulated into the NPs to protect them from biodegradation and enhance their biodistribution and transfer to the inflamed tissues. Targeted delivery to inflamed tissues may provide with acid-sensitive NPs such as acid-sensitive sheddable PEGylated solid-lipid NPs (SLN). The TNF-α-siRNA-SLN had high encapsulation efficacy up to 90% with a 5% burst release of siRNA. However, they showed superior anti-inflammatory efficacy than freemethotrexate, as well 68 . Other nanoplatforms that inhibit TNF-α are surface charge tuneable Besides, it has been proven that melatonin inhibits TNF-α production and also, it has beneficial potential to decline COVID-19 symptoms. One clinical trial on the efficacy of melatonin in COVID-19 patients has proven its efficacy 81 . In other words, melatonin modulates the immune system by acting on T cells and inhibiting of TNF-α 82 .

It has been proven the general administration of interferon-α needs a high dose of the parental regime and several severe side effects, therefore; encapsulation of the drug into a nanocarrier is of interest. For example, encapsulated interferon-α into chitosan NPs with mucoadhesive potential is promising to orally deliver the cargo. The NPs had a particle size of 36 nm without the decline of interferon-α activity into the carrier. Interferon-α -chitosan NP appear 1 h after the oral administration in plasma of mice while the commercial interferon-alpha was not detected. This finding showed that encapsulation of interferon-alpha into a NP remains its activity and enhances its biodistribution. However, the patients are more compatible with the oral administration of the injection 56 . Some other nanoplatforms that have been applied to produce interferon are a derivate of chitosan NPs 25, 83, 56, 59 Hydroxychloroquine is another drug that uses in COVID-19 patients through reduction of viral load and virus entrance to host cells. Therefore, encapsulation of the hydroxychloroquine into the nanocarriers that deliver cargo to the respiratory system and decline systemic administration side effects such as retinopathy, myopathy, and heart diseases is valuable. The nanocarriers can be liposomes, polymeric NPs same as albumin NPs, micelles, etc 57 

Overall, nanotechnology has emerged as a potent strategy for the designing of antiviral therapeutics. However, translation of extensive researches from bench to clinic is an urgent priority to control COVID-19. Noteworthy, we offer the repurposing of their nano-platforms.

These nanosystems have been summarized in table 3. Most recent R&D on coronavirus vaccines has been dedicated to RNA and protein vaccines containing the S RNA and protein subunits and explicitly targeting the receptor-binding domain (RBD) of the S1 subunit of the viral S protein. Modern vaccines composed of antigenic protein subunits, including viral S protein subunits, present higher neutralizing antibody and more protective immunity compared to a live-attenuated virus, full-length S protein, and DNA-based S protein vaccines. Therefore, spike RNA and protein segments are the preferred targets for SARS/MERS vaccine development, which can take advantage of the same approach in developing COVID-19 nanovaccines. From the other side, NPs are ideal carriers and therapeutics for pulmonary delivery 58 . In this point of view, blocking the S-ACE2 receptor interaction by biocompatible NPs would be promising; especially when the theranosticNPs are designed for early and fast detection and effective treatment, Nanomaterials can act as an adjuvant to enhance immunogenicity and antigen protection from biodegradation. These immune-targeted nanotherapeutics show dose spare, modulation of type of immunity, vast antibody responses, more rapid and durable immunity in vaccinated individuals 95 . Their responsiveness is size-dependent and, in some cases, may increase the immunity responses 100 folds higher than the soluble antigens. The NPs with 10-100 nm may be considered as a favourable particle size that can be deposited in the alveolar region, and lesser 95 than this size may be filtrated from the kidney. Nano-vaccines should act as a delivering and immunomodulatory system. To reach this goal, functionalization of nanomaterials with the ligands of TLR4 and NLRP3 and also dendritic cells' receptors such as 

Recently, due to the importance of limiting the virus pandemic in the world, the results of the effectiveness of a new drug are announced every day, which seems to be understandable, but it should be reviewed more wisely. Nano drugs, meanwhile, acts as a double-edged sword. interaction will be valuable to achieve this goal. Therefore, it appears that NPs themselves and also as a combination therapy system or carriers for the aim of drug repurposing and development will be promising in designing rapid test diagnosis methods and therapeutic agents. Host cell attachment and entry  --80  76  Orf3a  --92  72  Orf3b  --32  32  Envelope  protection  --100  95  Membrane  fusion  --99  91  Orf6  --94  69  Orf7a  --89  85  Orf7b  --93  81  Orf8a/8b  --94  40  Nucleoprotein Viral genome and proteins  --94  94  Orf9b  --73  73  Envelope  protection  --100  95  Membrane  fusion  --99  91  Orf6  --94  69  Orf7a  --89  85  Orf7b  --93  81  Orf8a/8b  --94  40  Nucleoprotein Viral genome and proteins  --94  94  Orf9b -- 73 73 

The MERS-CoV spike protein selectively binds to sialic acid (Sia), and cell-surface sialoglycoconjugates can serve as an attachment factor

Investigation of viral transmission and pathogenesis 34 

The importance of the S1 domain in MERS-CoV infection and tropism

Investigation of viral transmission and pathogenesis, speciesspecific colocalization of MERS-CoV entry and attachment receptors 35 Microneedle array (MNA) delivered SARS-CoV-2 S1 subunit vaccines

Targeting the S protein Strong and long-lasting antigen-specific antibody responses 36 J o u r n a l P r e -p r o o f Table 3 . The potential nano-based drugs repurposing for the treatment of COVID-19.

Lipid NPs TNF-α siRNA rheumatoid arthritis 68 Surface charge tunable (PEG5K-b-PLGA10K) nanoparticles TNF-α siRNA ulcerative colitis 69 Gold NPs (AuNGs) -collagen-induced arthritic (CIA) 70 Octadecylamine Sirolimus known as rapamycin Peripheral artery disease (PAD) 87 Sirolimus nanocomposites Sirolimus macrocyclic lactone immunosuppressant, antirejection reaction after organ transplantation 88 Sirolimus Nanocrystals Sirolimus the immunosuppressive agent also used to treat inflammation, cancer 89 Calcium phosphate (CaP) NP-based vaccine carrier functionalized with CpG and viral peptides -chronic retroviral infection 

Homology-based identification of a mutation in the coronavirus RNA-dependent RNA polymerase that confers resistance to multiple mutagens

CD147 as a target for COVID-19 treatment: suggested effects of azithromycin and stem cell engagement

Survival outcome and EMT suppression mediated by a lectin domain interaction of Endo180 and CD147

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment

Return of the Coronavirus: 2019-nCoV

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2

Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

Features, Evaluation and Treatment Coronavirus (COVID-19)

COVID-2019: The role of the nsp2 and nsp3 in its pathogenesis

Clinical Performance of RT-PCR and Chest CT Scan for Covid-19 Diagnosis; a Systematic Review

Detection of SARS-CoV-2 in Different Types of Clinical Specimens

Diagnosing COVID-19: The Disease and Tools for Detection

Evaluation of Enzyme-Linked Immunoassay and Colloidal Gold-Immunochromatographic Assay Kit for Detection of Novel Coronavirus (SARS-Cov-2) Causing an Outbreak of Pneumonia (COVID-19). medRxiv 2020. 17. Foundation TWN. COVID-19 Colloidal Gold Method Antibody Test

Dual-functional plasmonic photothermal biosensors for highly accurate severe acute respiratory syndrome coronavirus 2 detection

Pharmaceutical nanotechnology: which products are been designed against COVID-19?

Self-assembled star-shaped chiroplasmonic gold nanoparticles for an ultrasensitive chiro-immunosensor for viruses

Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus

Chapernamediated assembly of ferritin-based Middle East respiratory syndrome-coronavirus nanoparticles

Enhanced ability of oligomeric nanobodies targeting MERS coronavirus receptor-binding domain

Chimeric camel/human heavy-chain antibodies protect against MERS-CoV infection

A novel nanobody targeting Middle East respiratory syndrome coronavirus (MERS-CoV) receptor-binding domain has potent crossneutralizing activity and protective efficacy against MERS-CoV

Application of camelid heavy-chain variable domains (VHHs) in prevention and treatment of bacterial and viral infections

Nanobodies® as inhaled biotherapeutics for lung diseases

A self-adjuvanted nanoparticle based vaccine against infectious bronchitis virus

Heterologous prime-boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus

MERS-CoV spike nanoparticles protect mice from MERS-CoV infection

Novel coronavirus-like particles targeting cells lining the respiratory tract

Development of label-free colorimetric assay for MERS-CoV using gold nanoparticles

Multiplex paper-based colorimetric DNA sensor using pyrrolidinyl peptide nucleic acid-induced AgNPs aggregation for detecting MERS-CoV, MTB, and HPV oligonucleotides

Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein

Species-specific colocalization of Middle East respiratory syndrome coronavirus attachment and entry receptors

Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development

Toward Nanotechnology-Enabled Approaches against the COVID-19 Pandemic

Organelles and chromatin fragmentation of human umbilical vein endothelial cell influence by the effects of zeta potential and size of silver nanoparticles in different manners

Core/shell gel beads with embedded halloysite nanotubes for controlled drug release

Cytotoxicity and antiviral activity of electrochemical-synthesized silver nanoparticles against poliovirus

Nano-based approach to combat emerging viral (NIPAH virus) infection

Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism

Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly decimates human spleens and lymph nodes

Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases

Design and delivery of therapeutic siRNAs: application to MERS-Coronavirus

Immunomodulatory nanodiamond aggregate-based platform for the treatment of rheumatoid arthritis

Graphene-based materials for the fast removal of cytokines from blood plasma

Autophagy modulators: mechanistic aspects and drug delivery systems

Functional Carbon Quantum Dots as medical countermeasures to human Coronavirus

Novel Gold Nanorod-Based HR1 Peptide Inhibitor for Middle East Respiratory Syndrome Coronavirus

A molecular docking study repurposes FDA approved iron oxide nanoparticles to treat and control COVID-19 infection

Cellular nanosponges inhibit SARS-CoV-2 infectivity

Discovering drugs to treat coronavirus disease 2019 (COVID-19)

Drug treatment options for the 2019-new coronavirus (2019-nCoV)

Development of a drug delivery system based on chitosan nanoparticles for oral administration of interferon-α

Cavalcanti IMF, Lira Nogueira MCdB. Nanocarriers in the Delivery of Hydroxychloroquine to the Respiratory System: An Alternative to COVID-19

Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum

Oral Pharmacokinetics of a Chitosan-Based Nano-Drug Delivery System of Interferon Alpha

Nanomaterials designed for antiviral drug delivery transport across biological barriers

The effect of lopinavir/ritonavir and lopinavir/ritonavir loaded PLGA nanoparticles on experimental toxoplasmosis

Glutathione-capped Ag2S nanoclusters inhibit coronavirus proliferation through blockage of viral RNA synthesis and budding

Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry

Safety of testosterone treatment in postmenopausal women

Hierarchical porous carbide-derived carbons for the removal of cytokines from blood plasma

Optimizing use of theranostic nanoparticles as a life-saving strategy for treating COVID-19 patients

The SARS-CoV-2 S1 spike protein mutation N501Y alters the protein interactions with both hACE2 and human derived antibody: A Free energy of perturbation study

Lipid nanoparticles with minimum burst release of TNF-α siRNA show strong activity against rheumatoid arthritis unresponsive to methotrexate

Surface charge tunable nanoparticles for TNF-α siRNA oral delivery for treating ulcerative colitis

Nano-gold displayed anti-inflammatory property via NF-kB pathways by suppressing COX-2 activity. Artificial cells

Melatonin loading chitosan-tripolyphosphate nanoparticles: Application in attenuating etoposide-induced genotoxicity in HepG2 cells

Increased nose-to-brain delivery of melatonin mediated by polycaprolactone nanoparticles for the treatment of glioblastoma

Melatonin potentiates "inside-out" nano-thermotherapy in human breast cancer cells: a potential cancer target multimodality treatment based on melatonin-loaded nanocomposite particles

Preparation of Melatonin-Loaded Zein Nanoparticles using Supercritical CO2 Antisolvent and in vitro Release Evaluation

Melatonin/polydopamine nanostructures for collective neuroprotection-based Parkinson's disease therapy

Preparation of Mesalamine Nanoparticles Using a Novel Polyurethane-Chitosan Graft Copolymer

Formulation and performance of Irbesartan nanocrystalline suspension and granulated or bead-layered dried powders-Part I

Softtemplated fabrication of antihypertensive nano-Irbesartan: Structural and dissolution evaluation

Large-scale preparation of stable irbesartan nanoparticles by high-gravity liquid antisolvent precipitation technique

Solid lipid nanoparticles of irbesartan: preparation, characterization, optimization and pharmacokinetic studies

Clinical trials for use of melatonin to fight against COVID-19 are urgently needed

Inhibitory effect of melatonin on production of IFNγ or TNFα in peripheral blood mononuclear cells of some blood donors

Mesalazine/hydroxypropyl-βcyclodextrin/chitosan nanoparticles with sustained release and enhanced anti-inflammation activity

Cytotoxicity of 6-Mercaptopurine via Loading on PVA-Coated Magnetite Nanoparticles Delivery System: A New Era of Leukemia Therapy

Smart co-delivery of 6-mercaptopurine and methotrexate using disulphide-based PEGylated-nanogels for effective treatment of breast cancer

Glutathione-sensitive hyaluronic acidmercaptopurine prodrug linked via carbonyl vinyl sulfide: a robust and CD44-targeted nanomedicine for leukemia

Lnc-SNHG16/miR-128 axis modulates malignant phenotype through WNT/β-catenin pathway in cervical cancer cells

Amorphous nanoparticulate formulation of sirolimus and its tablets

Enhanced Bioavailability by Orally Administered Sirolimus Nanocrystals

Induction of type I interferons by therapeutic nanoparticle-based vaccination is indispensable to reinforce cytotoxic CD8+ T cell responses during chronic retroviral infection

COVID-19 Vaccines in Clinical Trials and their Mode of Action for Immunity against the Virus

Impaired heart contractility in Apelin gene-deficient mice associated with aging and pressure overload

A Unique Protein Self-Assembling Nanoparticle with Significant Advantages in Vaccine Development and Production

Expression and regulation of the neutral amino acid transporter B0AT1 in rat small intestine

Applications of nanomaterials as vaccine adjuvants

Crucial role of lateral size for graphene oxide in activating macrophages and stimulating pro-inflammatory responses in cells and animals

Trends and targets in antiviral phototherapy

Toxicity concerns of nanocarriers. Nanotechnology-Based Approaches for Targeting and Delivery of Drugs and Genes

Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles

New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?

Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats