Article updated on 11/01/2021 by Benedette Cuffari
Image Credit: Corona Borealis Studio/Shutterstock.com
As the quest for a COVID-19 vaccine continues, researchers working in other science areas such as nanotechnology have joined the battle against the virus.
In addition to being responsible for almost two million deaths as of 11 January 2021, the COVID-19 crisis has also mobilized the scientific community in a way that no other situation has before. Multiple disciplines are currently researching the virus, developing diagnosis and treatment methods or a modality to slow its spread.
Nanotechnology is being prepared for deployment in the fight against COVID-19 in a wide range of areas. A paper published in the journal ACS Nano looks at the different ways nanotechnology will be used. The authors describe nanotech use in fields as diverse as virology, biology, medicine, engineering, chemistry, and materials, and computational science.
The nanotechnology breakthroughs made in the coming months and years should bolster the resistance against COVID-19 and help fight against other viruses, bacteria, and pathogens.
The authors of the study identified four key stages at which nanotechnology could be introduced to help the battle against COVID-19:
- As an alternative to disinfectants preventing the virus spread
- In diagnostic procedures
- Delivering drugs to those already infected
- Suppressing the immune response of COVID-19 patients
What follows is a rundown of the developed methods that could be employed in future pandemics and epidemics, possibly preventing them from reaching global crisis status.
Slowing the Spread of COVID-19
The ongoing COVID-19 crisis does not mark the first time that nanomaterials have been highlighted for their ability to limit the spread of viruses. Surfaces coated with polymers containing metal nanoparticles such as copper can release metal ions known for their antiviral activity and have already been suggested for use in certain areas. The widespread nature of the COVID-19 crisis calls for a corresponding widespread application of such measures.
Nanotechnology offers a safer alternative to the use of toxic chemicals such as disinfectants in medical settings. Such coatings are far more convenient than other non-toxic disinfectant measures such as irradiation with ultraviolet (UV) light. These nanomaterial coatings and alloys confer antiviral and antibacterial properties through the release of ions, which disrupt living cells' operation.
One of the key difficulties in tackling COVID-19 is its hardiness and ability to survive on various surfaces for prolonged periods — often days on end. The beauty of a nanomaterial coating is that it could provide protection continuously after just one treatment. This is especially true if the material can be structured so that the release of ions is gradual. ‘Self-disinfecting’ surfaces would be of great use even after the COVID-19 crisis is over.
Silver, copper, and zinc all show intrinsic antimicrobial properties and are already used in medical equipment and healthcare settings.
In unison with our growing understanding of bacteria and viruses, silver nanoparticles (AgNPs) have found their way into commercial products such as silver zeolites in paints and in food trays as a biocide, with the antiviral efficiency of AgNPs demonstrated against a variety of viruses, including HIV-1. The antiviral effects of AgNPs are due to their ability to inhibit the multiplication of viruses and preventing the viral area in cells by directly interacting with cell receptors.
Copper was shown to be effective against polio in the late 1970s and, more recently, was of great use in combating another coronavirus, HuCoV-229E. The virus, which typically lives for around six days on a surface, became inactive in approximately 60 minutes on surfaces coated with copper alloys. The similarity between HuCoV-229E and SARS-CoV-2 points to copper nanoparticles and alloy coatings being a key-player in slowing, if not stopping, the spread.
The authors suggest that copper alloys could also find themselves replacing more traditional stainless steel surfaces and appliances in medical settings as a result of this non-toxic antibacterial agency.
Nanomaterials are also employed in the production of vitally important personal protective equipment (PPE) to help reduce the spread of COVID-19 to frontline medical workers. In particular, nanomaterials could be used in facemasks and other PPE to capture and immobilize viral cells. This task would likely fall upon silver nanoparticles, which have been shown effective in this respect, severely limiting viral activity when loaded into filters.
However, even if the spread of COVID-19 can be slowed by such coatings and a switch to copper alloys, another vital step in combating COVID-19 is efficient testing and diagnosis. Fortunately, nanomaterials are on hand to aid in this regard too.
Using Nanoparticles in COVID-19 Testing
The SARS-CoV-2 virus cannot be eliminated from all surfaces, and not all surfaces can be coated with a nanomaterial layer. This means that even with such measures, the transmission is very likely to continue. Therefore, the next step in slowing the spread is the quick and effective diagnosis of those already infected.
The current testing methodology for COVID-19 involves using a swab applied to the throat and nasal passage of a potential patient. This swab is then analyzed using a reverse transcription-polymerase chain reaction (RT-PCR) test — a procedure used in virology to test for the presence of specific RNA. RT-PCR is associated with limitations in its capacity and turnaround time, causing scientists to investigate alternative diagnostic approaches. For example, the use of nanoparticles could provide a more immediate ‘on-site’ test result without the need to send samples away for lab analysis or the need for expensive equipment.
Several different nanotechnology-based point of care (POC) immunodiagnostic devices that are portable, direct, and easy have been introduced as rapid SARS-CoV-2 detection methods. These devices analyze the immunocomplexation between monoclonal antibodies, primarily IgG or IgM, and SARS-CoV-2 antigens on a nitrocellulose membrane. The colloidal AuNPs that coat the test strip immobilize these mAbs to allow the SARS-CoV-2 antigens to be directed towards them for coupling. A patient sample containing specific antibodies to SARS-CoV-2 will react with the colored antigen-AuNP complex to generate a red signal visible to the naked eye, indicating a positive COVID-19 test result.
Compared to the discomfort that is often associated with the traditional COVID-19 swab test, this type of immunoassay instead requires only a few drops of blood that have been obtained from a finger prick to receive a diagnosis. The rapid detection potential and adaptability of these immunoassays have led several commercial companies worldwide to produce these immunodiagnostic kits for general use.
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AuNPs can also be used in nano biosensors, which combine the excellent electrical and optical properties of nanomaterials with biological or synthetic molecules used as receptors to detect specific whole viral cells selectively.
In one recent development, a team of researchers designed antisense oligonucleotide (ASO) probes to target two regions of the nucleocapsid phosphoprotein (N-gene) present on the SARS-CoV-2 virus. These ultrasensitive ASO probes are comprised of AuNPs that are capped with single-stranded deoxyribonucleic acid (ssDNA) material. This sensing probe hybridizes the viral RNA of SARS-CoV-2, and an electron transfer occurs that subsequently causes a change to arise in the sensor’s electrical response. The AuNP caps accelerate this charge transfer to provide a measurable output signal that is ultimately used by the device operator to determine when a sample is positive for SARS-CoV-2.
Another alternative to the currently favored RT-PCR that also relies upon the detection of antibodies includes graphene-based sensors. Such graphene-based biosensors comprise two components, the first of which consists of a platform that measures the electrical read-out of probes for viral RNA detection. Gold electrodes are then placed on top of the graphene platform as a contact pad for the electrical read-out. Both AuNPs and graphene are associated with exceptional sensitivity, selectivity, and conductivity properties, creating an ultrasensitive platform capable of detecting small changes in electrical signals that reflect whether SARS-CoV-2 genetic material is present in a given sample.
It should be noted that this is a field in its relative infancy, but any developments spearheaded in response to the COVID-19 crisis could be carried forward to future epidemics and pandemics.
Deactivating SARS-CoV-2 in Patients
The rapid spread of COVID-19 and the relative failure to tackle it has exposed a weakness in medicine: the lack of a broad-spectrum antiviral drug. That means that when a new virus emerges, there is little medical intervention that can be done to mitigate the spread. Therefore, drugs that could tackle both COVID-19 and future viruses are of the utmost importance.
Though other organs can be affected, the main target of COVID-19 once inside a sufferer's body is the respiratory system. The virus targets the upper respiratory tract and the lungs, with the latter being the most critically affected area.
Airborne nanomaterials are optimally suited to penetrate the deep-lung, suggesting their potential utility in delivering medicine directly to the cells that SARS-CoV-2 uses to spread further into a patient’s system. Since many of these therapeutic molecules are not stable in an aerosolized form, their combination with nano-delivery systems has allowed their administration to be possible through inhalation, enhancing the deposition and retention of these drugs directly to the lungs.
Nanomedicine is currently heavily researched to deliver drugs, therapeutic proteins, and even messenger RNA (mRNA) molecules through aerosol nano-devices.
A general antiviral nanomaterial intervention could work by preventing viruses from interacting with and binding to cell membranes. Previous work has shown that this could be achieved by a wealth of nanomaterials such as polymers, liposomes, and small molecules.
However, the implementation of these methods via aerosol has been hampered by the necessary dilution of these nanomaterials, negatively impacting their effectiveness. This loss of efficiency allows virus cells to begin replication again.
This setback can be combated by nanoparticles that, after introduction to a patient’s lungs or other organs, attack the virion —the infective form of a virus outside a host cell — permanently damaging it and preventing replication.
A specific COVID-19 drug administered similarly to the general antiviral treatment discussed above could be created by engineering it to block the S spike protein from interacting with the ACE2 receptor.
Part of the key to saving the lives of COVID-19 patients may not just hinge on attacking the virus but limiting the body’s response to it.
Suppressing the Immune Response with Nanotools
As a result of the COVID-19 crisis, many more people are familiar with the phrase ‘Cytokine Storm’. Cytokine storms are associated with various infectious and non-infectious diseases, particularly the H1N1 influenza strain. The term itself summons images of a terrible and violent reaction within the patient’s body, arising from their excessive immune response.
Although a well-regulated cytokine response that is rapidly triggered by the host’s innate immunity can prevent and counteract infection, an excessive, unbalanced, and prolonged immune response can seriously harm the body.
In many COVID-19 cases, this inflammatory storm is responsible for acute respiratory distress syndrome (ARDS), which is often associated with multiple organ failure and is a leading cause of death in critical patients.
Nanomaterials have been used to adjust the immune response, bringing it to an optimal level, and could be used to limit the cytokine storm. This can be done in several ways.
Firstly, nanotechnology can deliver immunosuppressants to target immune cells and organs, leading to reductions in drug dose, drug distribution to non-target tissues and organs, and, in-turn, unwanted side effects.
Secondly, nanotools can be explicitly designed to evade the immune system and finely tune the patient’s system to receive a high drug load that could otherwise trigger a harmful immune response.
Regarding COVID-19 specifically, the authors of the ACS Nano review point to the use of nanodiamonds to reduce macrophage infiltration — a process linked to inflammation.
COVID-19 and Beyond
COVID-19 has presented the scientific community with the kind of challenge it has perhaps never had to face before. However, it has also created the awareness that this situation could arise again.
While being engineered in response to this current crisis, the nanotech advancements described here are designed by scientists with the future in mind.
The authors of the ACS Nano review paper have a message to the general public, policy-makers, politicians, and the general scientific community: we must stop thinking of human health as an isolated phenomenon. Instead, we have to embrace the concept of ‘one health,’ with understanding that our well-being is intrinsically and irreversibly linked with the ecosystems we inhabit.
The field of nanotechnology points towards the benefits of adopting a holistic and inclusive attitude, spreading across many different aspects of science and bringing together scientists from diverse backgrounds, all converging on a multifaceted solution to a crisis that threatens our very way of life.
The study of nanotechnology could emerge such big ideas with the capability of changing the world.
References and Further Reading
Jindal, S., & Gopinath, P. (2020) Nanotechnology based approaches for combatting COVID-19 viral infection. Nano Express 1(2). doi:10.1088/2632-959X/abb714.
Weiss, C., Carriere, M., Fusco, L., et al. (2020) Toward Nanotechnology-Enabled Approaches against the COVID-19 Pandemic. ACS Nano. doi:10.1021/acsnano.0c03697.
Graphene-based electrochemical sensor can detect COVID-19 in less than five minutes [Online] Available from: https://www.graphene-info.com/graphene-based-electrochemical-sensor-can-detect-covid-19-less-five-minutes.
Mahapatra, S., & Chandra, P. (2020) Clinically practiced and commercially viable nanobio engineered analytical methods for COVID-19 diagnosis. Biosensors and Bioelectronics 165. doi:10.1016/j.bios.2020.112361.
Rangayasami, A., Kannan, K., Murugesan, S. (2021) Influence of nanotechnology to combat against COVID-19 for global health emergency: A review. Sensors International. doi:10.1016/j.sintl.2020.100079.
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