Piezoelectric Biosensors and Nanomaterials-based Therapeutics for Coronavirus and Other Viruses: A Mini-review.

Since late 2019, the novel coronavirus (COVID-19) pandemic has caused considerable mortality worldwide. This pandemic raised concerns and provoked research on the diagnosis and treatment of viruses-based diseases. The accurate diagnosis of a virus requires high specificity and sensitivity. Piezoelectric sensors are analytical devices that work on mass-sensitivity-based micromechanical transducers. The change in the mass by the interaction between biological elements and the frequency is recorded by measuring the alternate current and voltage. In addition to diagnosis, antiviral intervention strategies for mitigating various viral diseases are required. Nanomaterialsbased antiviral therapy is efficient, particularly with carbon/metal/metal oxide (organic/inorganic) nanoparticles. Metal/metal oxide nanoparticles, such as gold (Au), silver (Ag), copper (Cu), selenium (Se), zinc oxide (ZnO), magnesium oxide (MgO), carbon dots (CDs), and carbon quantum dots (CQDs), are promising candidates for antiviral therapy. This review discusses the piezoelectric sensors used to detect various viruses, including COVID-19, and the various organic and inorganic nanoparticles involved in the antiviral therapy.

Safety and Biodistribution of Nanoligomers Targeting the SARS-CoV-2 Genome for the Treatment of COVID-19.

As the world braces to enter its fourth year of the coronavirus disease 2019 (COVID-19) pandemic, the need for accessible and effective antiviral therapeutics continues to be felt globally. The recent surge of Omicron variant cases has demonstrated that vaccination and prevention alone cannot quell the spread of highly transmissible variants. A safe and nontoxic therapeutic with an adaptable design to respond to the emergence of new variants is critical for transitioning to the treatment of COVID-19 as an endemic disease. Here, we present a novel compound, called SBCoV202, that specifically and tightly binds the translation initiation site of RNA-dependent RNA polymerase within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, inhibiting viral replication. SBCoV202 is a Nanoligomer, a molecule that includes peptide nucleic acid sequences capable of binding viral RNA with single-base-pair specificity to accurately target the viral genome. The compound has been shown to be safe and nontoxic in mice, with favorable biodistribution, and has shown efficacy against SARS-CoV-2 in vitro. Safety and biodistribution were assessed using three separate administration methods, namely, intranasal, intravenous, and intraperitoneal. Safety studies showed the Nanoligomer caused no outward distress, immunogenicity, or organ tissue damage, measured through observation of behavior and body weight, serum levels of cytokines, and histopathology of fixed tissue, respectively. SBCoV202 was evenly biodistributed throughout the body, with most tissues measuring Nanoligomer concentrations well above the compound KD of 3.37 nM. In addition to favorable availability to organs such as the lungs, lymph nodes, liver, and spleen, the compound circulated through the blood and was rapidly cleared through the renal and urinary systems. The favorable biodistribution and lack of immunogenicity and toxicity set Nanoligomers apart from other antisense therapies, while the adaptability of the nucleic acid sequence of Nanoligomers provides a defense against future emergence of drug resistance, making these molecules an attractive potential treatment for COVID-19.

A nanomaterial targeting the spike protein captures SARS-CoV-2 variants and promotes viral elimination.

The global emergency caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can only be solved with effective and widespread preventive and therapeutic strategies, and both are still insufficient. Here, we describe an ultrathin two-dimensional CuInP2S6 (CIPS) nanosheet as a new agent against SARS-CoV-2 infection. CIPS exhibits an extremely high and selective binding capacity (dissociation constant (KD) < 1 pM) for the receptor binding domain of the spike protein of wild-type SARS-CoV-2 and its variants of concern, including Delta and Omicron, inhibiting virus entry and infection in angiotensin converting enzyme 2 (ACE2)-bearing cells, human airway epithelial organoids and human ACE2-transgenic mice. On association with CIPS, the virus is quickly phagocytosed and eliminated by macrophages, suggesting that CIPS could be successfully used to capture and facilitate virus elimination by the host. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, and as a decontamination agent and surface-coating material to reduce SARS-CoV-2 infectivity.

Nanoscale Technologies in the Fight against COVID-19: From Innovative Nanomaterials to Computer-Aided Discovery of Potential Antiviral Plant-Derived Drugs.

The last few years have increasingly emphasized the need to develop new active antiviral products obtained from artificial synthesis processes using nanomaterials, but also derived from natural matrices. At the same time, advanced computational approaches have found themselves fundamental in the repurposing of active therapeutics or for reducing the very long developing phases of new drugs discovery, which represents a real limitation, especially in the case of pandemics. The first part of the review is focused on the most innovative nanomaterials promising both in the field of therapeutic agents, as well as measures to control virus spread (i.e., innovative antiviral textiles). The second part of the review aims to show how computer-aided technologies can allow us to identify, in a rapid and therefore constantly updated way, plant-derived molecules (i.e., those included in terpenoids) potentially able to efficiently interact with SARS-CoV-2 cell penetration pathways.

Antiviral effects of coinage metal-based nanomaterials to combat COVID-19 and its variants.

The world has been suffering from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and millions of people have been infected through human-to-human transmission and lost their lives within months. Although multidisciplinary scientific approaches have been employed to fight against this deadly pandemic, various mutations and diverse environments keep producing constraints in treating SARS-CoV-2. Indeed, the efficacy of the developed vaccines has been limited, and inoculation with the vaccines does not guarantee complete protection even though multiple doses are required, which is a frustrating process. Historically, coinage metals (Cu, Ag, and Au) have been well-known for their effectiveness in antiviral action as well as good biocompatibility, binding receptor inhibition, reactive oxygen species, and phototherapy properties. Thus, this review highlights the diagnostic and therapeutic mechanisms of SARS-CoV-2 using the antivirus ability and mode of action of coinage metals such as viral entry mechanisms into host cells and the NP-inhibition process, which are explained in detail. This article also draws attention to coinage metal nanomaterial-based approaches to treat other contagious viruses. In addition, coinage metal-based biosensors and an overview of some other biocompatible metal-based nanomaterials to fight against SARS-CoV-2 variants are discussed. Finally, the advantages, perspectives and challenges of coinage metal nanoparticles are given to fight against viral infections in the future.

Advances in Nanomaterial-Based Platforms to Combat COVID-19: Diagnostics, Preventions, Therapeutics, and Vaccine Developments.

The COVID-19 pandemic caused by the SARS-CoV-2, a ribonucleic acid (RNA) virus that emerged less than two years ago but has caused nearly 6.1 million deaths to date. Recently developed variants of the SARS-CoV-2 virus have been shown to be more potent and expanded at a faster rate. Until now, there is no specific and effective treatment for SARS-CoV-2 in terms of reliable and sustainable recovery. Precaution, prevention, and vaccinations are the only ways to keep the pandemic situation under control. Medical and scientific professionals are now focusing on the repurposing of previous technology and trying to develop more fruitful methodologies to detect the presence of viruses, treat the patients, precautionary items, and vaccine developments. Nanomedicine or nanobased platforms can play a crucial role in these fronts. Researchers are working on many effective approaches by nanosized particles to combat SARS-CoV-2. The role of a nanobased platform to combat SARS-CoV-2 is extremely diverse (i.e., mark to personal protective suit, rapid diagnostic tool to targeted treatment, and vaccine developments). Although there are many theoretical possibilities of a nanobased platform to combat SARS-CoV-2, until now there is an inadequate number of research targeting SARS-CoV-2 to explore such scenarios. This unique mini-review aims to compile and elaborate on the recent advances of nanobased approaches from prevention, diagnostics, treatment to vaccine developments against SARS-CoV-2, and associated challenges.

Recent ultrasound advancements for the manipulation of nanobiomaterials and nanoformulations for drug delivery.

Recent advances in ultrasound (US) have shown its great potential in biomedical applications as diagnostic and therapeutic tools. The coupling of US-assisted drug delivery systems with nanobiomaterials possessing tailor-made functions has been shown to remove the limitations of conventional drug delivery systems. The low-frequency US has significantly enhanced the targeted drug delivery effect and efficacy, reducing limitations posed by conventional treatments such as a limited therapeutic window. The acoustic cavitation effect induced by the US-mediated microbubbles (MBs) has been reported to replace drugs in certain acute diseases such as ischemic stroke. This review briefly discusses the US principles, with particular attention to the recent advancements in drug delivery applications. Furthermore, US-assisted drug delivery coupled with nanobiomaterials to treat different diseases (cancer, neurodegenerative disease, diabetes, thrombosis, and COVID-19) are discussed in detail. Finally, this review covers the future perspectives and challenges on the applications of US-mediated nanobiomaterials.

Surface Glycan Modification of Cellular Nanosponges to Promote SARS-CoV-2 Inhibition.

Cellular binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mediated by its spike glycoprotein (S protein), which binds with not only the human angiotensin-converting enzyme 2 (ACE2) receptor but also glycosaminoglycans such as heparin. Cell membrane-coated nanoparticles ("cellular nanosponges") mimic the host cells to attract and neutralize SARS-CoV-2 through natural cellular receptors, leading to a broad-spectrum antiviral strategy. Herein, we show that increasing surface heparin density on the cellular nanosponges can promote their inhibition against SARS-CoV-2. Specifically, cellular nanosponges are made with azido-expressing host cell membranes followed by conjugating heparin to the nanosponge surfaces. Cellular nanosponges with a higher heparin density have a larger binding capacity with viral S proteins and a significantly higher inhibition efficacy against SARS-CoV-2 infectivity. Overall, surface glycan engineering of host-mimicking cellular nanosponges is a facile method to enhance SARS-CoV-2 inhibition. This approach can be readily generalized to promote the inhibition of other glycan-dependent viruses.

Emerging nanomaterials applied for tackling the COVID-19 cytokine storm.

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.

Hard Nanomaterials in Time of Viral Pandemics.

The SARS-Cov-2 pandemic has spread worldwide during 2020, setting up an uncertain start of this decade. The measures to contain infection taken by many governments have been extremely severe by imposing home lockdown and industrial production shutdown, making this the biggest crisis since the second world war. Additionally, the continuous colonization of wild natural lands may touch unknown virus reservoirs, causing the spread of epidemics. Apart from SARS-Cov-2, the recent history has seen the spread of several viral pandemics such as H2N2 and H3N3 flu, HIV, and SARS, while MERS and Ebola viruses are considered still in a prepandemic phase. Hard nanomaterials (HNMs) have been recently used as antimicrobial agents, potentially being next-generation drugs to fight viral infections. HNMs can block infection at early (disinfection, entrance inhibition) and middle (inside the host cells) stages and are also able to mitigate the immune response. This review is focused on the application of HNMs as antiviral agents. In particular, mechanisms of actions, biological outputs, and limitations for each HNM will be systematically presented and analyzed from a material chemistry point-of-view. The antiviral activity will be discussed in the context of the different pandemic viruses. We acknowledge that HNM antiviral research is still at its early stage, however, we believe that this field will rapidly blossom in the next period.

Large-Sized Graphene Oxide Nanosheets Increase DC-T-Cell Synaptic Contact and the Efficacy of DC Vaccines against SARS-CoV-2.

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.

Emerging nanotechnology role in the development of innovative solutions against COVID-19 pandemic.

The COVID-19 outbreak is creating severe impressions on all facets of the global community. Despite strong measures worldwide to try and re-achieve normalcy, the ability of SARS-CoV-2 to survive sturdy ecological settings may contribute to its rapid spread. Scientists from different aspects of life are working together to develop effective treatment strategies against SARS-CoV-2. Apart from using clinical devices for patient recovery, the key focus is on developing antiviral drugs and vaccines. Given the physical size of the SARS-CoV-2 pathogen and with the vaccine delivery platform currently undergoing clinical trials, the link between nanotechnology is clear, and previous antiviral research using nanomaterials confirms this link. Nanotechnology based products can effectively suppress various pathogens, including viruses, regardless of drug resistance, biological structure, or physiology. Thus, nanotechnology is opening up new dimensions for developing new strategies for diagnosing, preventing, treating COVID-19 and other viral ailments. This article describes the application of nanotechnology against the COVID-19 virus in terms of therapeutic purposes and vaccine development through the invention of nanomaterial based substances such as sanitizers (handwashing agents and surface disinfectants), masks and gowns, amongst other personal protective equipment, diagnostic tools, and nanocarrier systems, as well as the drawbacks and challenges of nanotechnology that need to be addressed.

High-performance antiviral nano-systems as a shield to inhibit viral infections: SARS-CoV-2 as a model case study.

Despite significant accomplishments in developing efficient rapid sensing systems and nano-therapeutics of higher efficacy, the recent coronavirus disease (COVID-19) pandemic is not under control successfully because the severe acute respiratory syndrome virus (SARS-CoV-2, original and mutated) transmits easily from human to -human and causes life-threatening respiratory disorders. Thus, it has become crucial to avoid this transmission through precautions and keep premises hygienic using high-performance anti-viral nanomaterials to trap and eradicate SARS-CoV-2. Such an antiviral nano-system has successfully demonstrated useful significant contribution in COVID-19 pandemic/endemic management effectively. However, their projection with potential sustainable prospects still requires considerable attention and efforts. With this aim, the presented review highlights various severe life-threatening viral infections and the role of multi-functional anti-viral nanostructures with manipulative properties investigated as an efficient precative shielding agent against viral infection progression. The salient features of such various nanostructures, antiviral mechanisms, and high impact multi-dimensional roles are systematically discussed in this review. Additionally, the challenges associated with the projection of alternative approaches also support the demand and significance of this selected scientific topic. The outcomes of this review will certainly be useful to motivate scholars of various expertise who are planning future research in the field of investigating sustainable and affordable high-performance nano-systems of desired antiviral performance to manage not only COVID-19 infection but other targeted viral infections as well.

Polymer-based nano-therapies to combat COVID-19 related respiratory injury: progress, prospects, and challenges.

The recent coronavirus disease-2019 (COVID-19) outbreak has increased at an alarming rate, representing a substantial cause of mortality worldwide. Respiratory injuries are major COVID-19 related complications, leading to poor lung circulation, tissue scarring, and airway obstruction. Despite an in-depth investigation of respiratory injury's molecular pathogenesis, effective treatments have yet to be developed. Moreover, early detection of viral infection is required to halt the disease-related long-term complications, including respiratory injuries. The currently employed detection technique (quantitative real-time polymerase chain reaction or qRT-PCR) failed to meet this need at some point because it is costly, time-consuming, and requires higher expertise and technical skills. Polymer-based nanobiosensing techniques can be employed to overcome these limitations. Polymeric nanomaterials have the potential for clinical applications due to their versatile features like low cytotoxicity, biodegradability, bioavailability, biocompatibility, and specific delivery at the targeted site of action. In recent years, innovative polymeric nanomedicine approaches have been developed to deliver therapeutic agents and support tissue growth for the inflamed organs, including the lung. This review highlights the most recent advances of polymer-based nanomedicine approaches in infectious disease diagnosis and treatments. This paper also focuses on the potential of novel nanomedicine techniques that may prove to be therapeutically efficient in fighting against COVID-19 related respiratory injuries.

Nanotechnology against the novel coronavirus (severe acute respiratory syndrome coronavirus 2): diagnosis, treatment, therapy and future perspectives.

COVID-19, as an emerging infectious disease, has caused significant mortality and morbidity along with socioeconomic impact. No effective treatment or vaccine has been approved yet for this pandemic disease. Cutting-edge tools, especially nanotechnology, should be strongly considered to tackle this virus. This review aims to propose several strategies to design and fabricate effective diagnostic and therapeutic agents against COVID-19 by the aid of nanotechnology. Polymeric, inorganic self-assembling materials and peptide-based nanoparticles are promising tools for battling COVID-19 as well as its rapid diagnosis. This review summarizes all of the exciting advances nanomaterials are making toward COVID-19 prevention, diagnosis and therapy.

Antiviral Activity of Nanomaterials against Coronaviruses.

One of the challenges facing by world nowadays is the generation of new pathogens that cause public health issues. Coronavirus (CoV) is one of the severe pathogens that possess the RNA (ribonucleic acid) envelop, and extensively infect humans, birds, and other mammals. The novel strain "SARS-CoV-2" (severe acute respiratory syndrome coronavirus-2) causes deadly infection all over the world and presents a pandemic situation nowadays. The SARS-CoV-2 has 40 different strains that create a worrying situation for health authorities. The virus develops serious pneumonia in infected persons and causes severe damage to the lungs. There is no vaccine available for this virus up to present. To cure this type of infections by making vaccines and antiviral drugs is still a major challenge for researchers. Nanotechnology covering a multidisciplinary field may find the solution to this lethal infection. The interaction of nanomaterials and microorganisms is considered as a potential treatment method because the nanomaterials owe unique physicochemical properties. The aim of this review is to present an overview of previous and recent studies of nanomaterials against coronaviruses and to provide possible new strategies for upcoming research using the nanotechnology platform.

COVID-19 vaccine development and a potential nanomaterial path forward.

The COVID-19 pandemic has infected millions of people with no clear signs of abatement owing to the high prevalence, long incubation period and lack of established treatments or vaccines. Vaccines are the most promising solution to mitigate new viral strains. The genome sequence and protein structure of the 2019-novel coronavirus (nCoV or SARS-CoV-2) were made available in record time, allowing the development of inactivated or attenuated viral vaccines along with subunit vaccines for prophylaxis and treatment. Nanotechnology benefits modern vaccine design since nanomaterials are ideal for antigen delivery, as adjuvants, and as mimics of viral structures. In fact, the first vaccine candidate launched into clinical trials is an mRNA vaccine delivered via lipid nanoparticles. To eradicate pandemics, present and future, a successful vaccine platform must enable rapid discovery, scalable manufacturing and global distribution. Here, we review current approaches to COVID-19 vaccine development and highlight the role of nanotechnology and advanced manufacturing.

Are graphene and graphene-derived products capable of preventing COVID-19 infection?

The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) causes the new coronavirus disease 2019 (COVID-19). This disease is a severe respiratory tract infection that spreading rapidly around the world. In this pandemic situation, the researchers' effort is to understand the targets of the virus, mechanism of their cause, and transmission from animal to human and vice-versa. Therefore, to support COVID-19 research and development, we have proposed approaches based on graphene and graphene-derived nanomaterials against COVID-19.

Can nanotechnology help in the fight against COVID-19?

INTRODUCTION: The current COVID-19 pandemic caused by the SARS-CoV-2 virus demands the development of strategies not only to detect or inactivate the virus, but to treat it (therapeutically and prophylactically). COVID-19 is not only a critical threat for the population with risk factors, but also generates a dramatic economic impact in terms of morbidity and the overall interruption of economic activities. AREAS COVERED: Advanced materials are the basis of several technologies that could diminish the impact of COVID-19: biosensors might allow early virus detection, nanosized vaccines are powerful agents that could prevent viral infections, and nanosystems with antiviral activity could bind the virus for inactivation or destruction upon application of an external stimulus. Herein all these methods are discussed under the light of cutting-edge technologies and the previously reported prototypes targeting enveloped viruses similar to SARS-CoV-2. This analysis was derived from an extensive scientific literature search (including pubmed) performed on April 2020. EXPERT OPINION: Perspectives on how biosensors, vaccines, and antiviral nanosystems can be implemented to fight COVID-19 are envisioned; identifying the approaches that can be implemented in the short term and those that deserve long term research to cope with respiratory viruses-related pandemics in the future.