As we all know, the world is suffering from a pandemic right now. Isn’t it fascinating that how a microorganism that we can’t even see with a naked eye, can affect the whole world? Yes, I am talking about the novel coronavirus SARS-CoV-2 which is responsible for Coronavirus Disease 2019 (COVID-19).
Scientists from all around the world are focused on finding an effective way to fight this coronavirus. Sadly, there is no antiviral drug or therapy which has been proved 100% effective against this virus resulting in a drastic increase in the no. of cases day by day. So, in this global emergency, we cannot rely on producing effective antiviral drugs or vaccines in the conventional way, which requires years of research and clinical testing before they can be marketed.
That is why multidisciplinary research efforts are required to improve the safety and efficacy of antiviral drugs and to develop alternatives for antiviral therapies. In this regard, nanotechnology is gaining attention because it has the potential to help us fight the virus-like no other technology can.
Nanotechnology, which was not very popular a few years back but now the applications of nanotechnology have been expanded to the areas beyond our expectations. Nanotechnology deals with materials and devices which have at least one dimension less than 100 nanometers. In the medical field, the applications of nanotechnology are termed nanomedicine, where it has been used for the diagnosis, treatment, control, and prevention of various diseases. But of all sizes, why Nano? First of all, SARS-CoV-2 itself is nanosized (60-140nm), which clearly suggests a direct combat strategy by using nanoparticles of a similar size. Secondly, most of the FDA-approved nanoparticles are under this size range.
Nanoparticles have unique properties which make them very attractive such as small size, larger surface area, multifunctionality, controlled release of drugs, and the ability to carry the drugs to their target sites in the body without the fear of degradation in the way.
PPE and disinfection
Covid-19 is very contagious as we know that SARS-CoV-2 can spread from person to person through microdroplets or direct contact with the infected person or the contaminated surface. Many reports have suggested that this virus can persist on the surface for 3 hours to even 9 days depending upon the type of surface and can even survive high temperatures too. So, we must improve our sterilization or disinfection systems if we want to control the spread of coronavirus.
Nanotechnology has come to rescue us by providing a large no. of opportunities for developing more efficient disinfection systems. Some nanomaterials have self-cleaning properties, the surfaces made from these types of materials have antimicrobial properties and they are able to release disinfectants upon some stimuli. For example, a formulation of titanium dioxide and silver nanoparticles has been proved very successful as a disinfectant upon induction by a photothermal signal. A high-efficiency sanitizer has also been patented which is composed of polymeric nanoparticles with excellent germicidal activity.
Nanotechnology is also paving our way towards the production of better personal protective equipment (PPE) in terms of both safety and comfort without affecting the texture of the fabric or its breathability. One strategy could be building hydrophobicity in the PPE products. Nanowhiskers are nanosized fibers that can be used to induce hydrophobicity in textiles by increasing the surface tension and lowering the rate of absorption of droplets onto them. Nanoparticles can also kill microorganisms by oxidating their membrane. The first act as a filter, trap them, and then kill or deactivate them.
This might shock some of you, but the face masks you wear daily due to the fear of viruses can only provide protection against particles above 100-300nm. So, if you are wearing a mask, it doesn’t mean you cannot be infected. Face masks made with nanofibers can provide us guaranteed protection against particles smaller than 50nm, and also improves the breathing comfort for the user. There are some patents on nanoparticle-based PPE such as MVX nano mask, the Guardian masks, Everyday protect gloves L. and many others. These products include blends of silver, titanium, copper, and zinc nanoparticles along with different types of fabrics for self-cleaning and antimicrobial properties.
There are many tests and assays available to check the presence of disease or virus in the body but still, their accuracy and reliability are questionable in some cases. Nanoparticles such as carbon nanotubes, quantum dots, and metallic nanoparticles have been used for the effective and fast detection of coronavirus. This is done by modifying the nanoparticle surface with viral RNA, antibody, or protein so that it will attach to the target site in the sample.
For example, by attaching SARS-CoV-2 specific IgG and IgM antibodies with the gold nanoparticles, we can even detect the asymptomatic COVID-19 cases along with the symptomatic ones. These hybrid systems are widely being used in nanosensors. One such system includes the use of gold nanoparticles functionalized with the oligonucleotides of N protein of SARS-CoV-2. When mixed with the sample, and examined under UV spectrophotometer, the aggregates of nanoparticles with the target can easily be detectable within 10 mins of performance.
In another nano biosensor, graphene nanosheets are used which are functionalized with S protein of SARS-CoV-2 and it is able to detect the virus in the swab samples of patients within minutes. So, in this pandemic, nanobiosensors have become a new sensation for the fast, cost-effective, and easy detection of coronavirus.
Drug delivery and control of virus
There are many concerns associated with the antiviral drugs such as low bioavailability, narrow spectrum, toxicity, prone to degradation and off target effects. For example, hydroxychloroquine which is commonly prescribed to COVID-19 patients can cause toxicity in heart, liver, and central nervous system. So, the efficacy of antiviral drugs can be enhanced by making them organ specific and decreasing their toxicity. There comes the role of nanotechnology because many types of nanoparticles such as polymeric, metallic and quantum dots can be used to make antiviral therapies more reliable and efficient.
Nanoparticles for virus inhibition
Virus and nanoparticles, both are in the nanometer size range. So, nanoparticles of size which is closest to the size of the virus can be used to deliver antiviral drugs so they can interact better with the virus and their bioavailability can be enhanced. Nanoparticle- antiviral drug combination also improves the pharmacokinetics, bioavailability, and stability of the drug and also ensures their controlled release. Ligands for the specific target can be attached to nanocarriers for their organ/tissue-specific activity.
Nanoparticles with ligands specific to certain organs or tissue can also be used to block the cell receptors so that virus can not bind to them to make an entry into the cell. Many viruses including SARS-CoV-2, bind with the cell surface receptors called heparan sulfate proteoglycans (HSPG) to make an entry into the cell. Gold nanoparticles capped with mercaptoethanesulfonate or gold nanoparticles coated with sulfonic acid mimic the HSPG receptors so that the virus will bind to the gold nanoparticle instead of the actual cell receptor.
These strategies have been proved successful against many viral infections by inhibiting their entry and spread inside the body. A similar approach can be used to combat SARS-CoV-2 infection because they also use HSPG for their entry inside the cells.
Small interfering RNA (siRNA) therapy is also a very effective approach to control SARS-CoV-2. In pre-clinical trials, siRNA against the S protein or 3′ UTR of SARS-CoV-2 has been proved successful in reducing the pathogenicity and replication of virus. The conserved regions in the genome of SARS-CoV-1 and SARS-CoV-2 are also the target for siRNA therapy. But the problem is siRNA is a very unstable molecule, plus its negative charge make it hard to cross the cell membrane.
SiRNA is also prone to degradation by enzymes. That is why lipid or polymeric nanoparticles can be used for their safe and effective delivery to their specific target sites. The role of CRISPR/Cas9 has also been explored for the containment of SARS-CoV-2. Nanotechnology can also contribute is this area by providing the opportunity for the effective delivery of cas9 ribonucleoprotein which will improve the efficacy and decrease the time of the procedure.
Nanoparticles can also be functionalized with ligands specific for the receptors of virus. According to a study, carbon quantum dots (CDC) functionalized with boronic acid were able to interact with the viral surface receptors and with the S protein of human coronavirus HCoV-229E. These CDC inhibited the viral entry and replication by interacting with the S protein or factors required for viral entry. The similar approach can be used in the case of SARS-CoV-2 to block its entry in the cells and stop the infection at different stages.
Nanotherapy for the cytokine storm
Cytokine storm means the excessive production of pro-inflammatory cytokines due to hyper activation of immune system and this is a very common complication associated with COVID-19. One strategy to deal with this problem is inhibiting the recruitment of monocytes at the site of inflammation. Where there is inflammation, monocytes are attracted towards this area. They use CCR2 receptors to detect and bind with chemo and cytokines. Small interfering RNA (siRNA), specific for CCR2 mRNA can be encapsulated in lipid nanoparticles and upon delivery, they will bind with their complementary mRNA, and it will eventually be degraded by RNAases.
In this way, monocytes will not be able to recognize cytokines and their recruitment can be controlled. Cytokine storm can also be treated with nanoparticle-based immunotherapy such as the delivery of Interleukin-10 with the help of nanoparticles. Polymeric and gold nanoparticles can also be used for the effective delivery of immunotherapeutic drugs against cytokine storms.
Nano based vaccines
In this pandemic, everyone is waiting for a vaccine that is safe and highly efficient. Conventionally, it takes 10-15 years for a vaccine to come in market, form discovery to its commercialization. This procedure is very lagging as we have to stop this virus as soon as possible. Nano-based vaccines are a new class of vaccines which are gaining attention by providing unique properties that make them safer, and more efficient than conventional vaccines. Nanobased vaccines provide protection to antigens against degradation, increase their stability, ensure sustained release, deliver them target specifically and increase the antigen exposure to APCs for their presentation. But above of all, nanobased vaccines are able to elicit both the cellular and antibody immune response, which make them highly immunogenic.
Due to the similar size, nanoparticles work in the same way as the virus does but nanoparticles are more specific towards their target cells and even subcellular locations. These antigen nanocarriers can be made by polymeric, lipid, or polysaccharide nanoparticles. Lipid-based nanocarriers encapsulating the nucleic acid-based antigens protect them from degradation by enzymes and also improve their immunogenicity by increased cell uptake. Antigens can also be adsorbed on the surface of the nanoparticle, or together with the adjuvant. Moreover, nanoparticles natively have adjuvant properties which make them even more attractive for antigen delivery. Nanoparticles have tunable properties such as size, shape, charge, and functional groups to make them target specific and also biocompatible with the body.
There is an urgent need for the SARS-CoV-2 vaccine but none of the vaccines that are commercially available are 100% efficient. S protein of SARS-CoV-2 or the subunits of this protein such as receptor binding domain (RBD) or N terminal domain are believed to be the best antigens to elicit the immune response against the virus. Cocktail vaccines containing the mixture of nucleoprotein and non-structural viral proteins as antigens have also been made by Epivax but they are less efficient. Nanovax have also made a vaccine made from the full-length S protein combined with Matrix-M™ adjuvant which has been proved successful in pre-clinical trials.
In the last, I think nanotechnology has the potential to save us from this pandemic. But there is more research and development required in this area to better understand the fate, behavior, and toxicokinetic behavior of these nanoparticles once they are inside the body. It is necessary that these new technologies should be focused on by the research groups and companies to develop more efficient, safer, and robust methods to deal with this pandemic.
mRNA based vaccines against SARS-CoV-2 are so far the most efficient vaccines against the virus. These include Moderna mRNA-1273 and Pfizer BioNTech BNT162b2 vaccine with 94.5% and 95% efficacy, respectively. These vaccines work by delivering the mRNA of S protein of SARS-CoV-2 inside the host cell, then this mRNA is translated by the host machinery into viral spike protein which generates an immune response against it.
The main problem regarding these mRNA vaccines is the delivery of mRNA inside the cell, its stability, and the protection of mRNA from RNA degrading enzymes. To solve this problem, FDA-approved lipid nanoparticles have been used as nanocarriers in Moderna and Pfizer vaccine which is the main reason behind their success and effectiveness. According to reports, there are 19 nano-based vaccine candidates for preventing COVID-19 that are under research and development. The results of their pre-clinical and clinical trials are eagerly awaited.
MS Industrial Biotechnology
Atta-ur-Rehman School of Applied Biosciences – NUST