Nanotechnological Applications in Virology

By Mahendra Rai

Nanotechnological Applications in Virology explores the use of nanoparticles-based technologies to fight against viruses, also discussing the use of nanoparticles in the preparation of nano masks and as sanitizing agents. The role of nanotechnology against HIV, Hepatitis, Influenza, Herpes, Ebola and Zika using rapid detection and diagnostic techniques is included, as is a brief description of SARS, MERS, the novel Coronavirus, and recent advancements in its treatment process. Other sections cover the formulation of novel nano-vaccines for the treatment and control of viral infections like HIV, Hepatitis and COVID-19. Included toxicological studies of nanoparticles provide readers with a brief overview on global scenarios regarding viral infections.

Nanotechnology is the present age technology, with wide usage in different areas of medical science, including drug delivery, gene therapy, antimicrobials, biosensors and bio-labelling. Nanoparticles play a competent role as an anti-infection agent and thus act as efficient antiviral agents.

• Mitochondria as a Key Intracellular Target of Thallium Toxicity presents a new hypothesis that explains the decrease in antioxidant defense in thallium poisoning. In addition, the book proposes a new model for studying the transport of inorganic cations across the inner mitochondrial membrane. Readers will learn about the toxicity of thallium and its compounds, the toxicology of thallium, the toxic thallium effects on cells, and the effects of thallium on mitochondria. This book+J136 lists the pathways and mechanisms of thallium transport into cells and mitochondria. This toxicity has been analyzed at both the cellular and subcellular levels
• The increase in human contact with the toxic trace element thallium is associated with developments in industry, the release of this metal into the environment from various rocks, and the use of special isotope techniques for studying the vascular bed

• Language: English
• Publisher: Academic Press
• Release date: Jun 23, 2022
• ISBN: 9780323995979

Book preview

Preface

Mahendra Rai

Alka Yadav

Viruses are infectious agents responsible for high mortality rates throughout the world and socioeconomic losses. Though viruses require a host for their existence, still virus-based infections claim several lives. A few examples of infections caused due to viruses include Influenza, Hepatitis, HIV, Zika, Nipah, SARS, MERS, and COVID-19.

Nanotechnology implies the use of nanoparticles in the dimension of 1–100-nm nanoscale range. Nanoparticle-based technology has been widely used in different fields of medicine, diagnostics and detection, and delivery of nanoparticles. The lack of effective drugs for most viral infections highlights the need for the development of rapid and accurate diagnostic kits, vaccine design and development, and virus tracking within the host cells. Nanotechnology offers rapid, sensitive, and accurate detection of viruses using diagnostic kits. The extremely small size of nanoparticles provide a surface area to the particles and entry into the living system. Also, the strong encapsulation of nanoparticles ensures the targeted delivery of drugs. Recently, the use of nanoparticles in the development of detection kits for COVID-19 has helped in the early diagnosis of the infection within a short period of time. Substantial development has been observed in the efficient delivery of drugs and vaccines and virus tracking in host cells. These applications of nanoparticles prove advantageous in providing rapid and sensitive detection, early confirmation of infection, and improved chances of recovery. Based on their smaller size, nanoparticles can effectively cross the blood-brain barrier and deliver the drug to the targeted site. Different types of nanoparticles such as silver nanoparticles, gold nanoparticles, copper nanoparticles, zinc nanoparticles, quantum dots, liposomes, dendrimers, and carbon nanotubes have successfully been used in various therapeutic applications. In the current scenario, where the whole world is fighting the SAS-CoV-2 pandemic, nanotechnology offers a promising approach in overcoming the barriers of traditional treatment processes.

This book provides an insight on different viral infections such as influenza, hepatitis, HIV, SARS, MERS, and Zika with special attention paid to the novel coronavirus. Further, different nanotechnological applications in the detection and diagnosis of viruses, the development of vaccines, and other therapeutic applications have been explicitly discussed.

The book is divided into five sections. Section I explains the different applications of nanotechnology against viruses. Section II highlights the use of nanotechnological tools for the detection and inhibition of viruses. Section III briefs about the role of nanotechnology in the targeted delivery of drugs. Section IV introduces SARS, MERS, and SARS-CoV-2, their origin, pathology, and use of nanotechnology in diagnosis and vaccine development for the viral infection. Section V focuses on vaccines formulated using nanoparticles.

This book will be helpful for the students and researchers working in the area of viral infection, nanotechnological tools and techniques against viruses, therapeutics, drug delivery, and vaccine development.

We take this opportunity to offer our sincere gratitude to all the contributors for their endless support and cooperation in providing the chapters. We also express our heartfelt thanks to Linda Versteeg-Buschman (Senior Acquisition Editor) and the entire team of Elsevier for their efforts, timely help, and cooperation in the publication of this book.

Chapter 1: Nanotechnological applications in old and emerging viral infections: Opportunities and challenges

Alka Yadava; Patrycja Golinskab; Mahendra Raia,b    a Nanobiotechnology Laboratory, Department of Biotechnology, Sant Gadge Baba Amravati University, Amravati, Maharashtra, India

b Department of Microbiology, Nicolaus Copernicus University, Torun, Poland

Abstract

Nanotechnology is the recent emerging technology in the field of therapeutics and diagnostics. Nanomaterials play a crucial role in diagnosis, drug delivery, drug formulations, and therapy to overcome several life-threatening diseases like diabetes, cancer, bacterial and fungal infections, neurodegenerative diseases, and AIDS. Viruses and viral infections are problematic due to their wide-spreading nature and also the ability to sustain the development through genetic mutation. In the last few decades, the cases of viral infections have severely increased including SARS severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), Nipah virus, Zika virus, dengue fever, and the recent global pandemic COVID-19. These episodes of viral epidemics have emerged unexpectedly and caused substantial damage to the social and economic structure of society. Due to the high mortality rate and global transmission capacity viral infections need immediate attention for the development of detection, treatment, and vaccination techniques.

Nanoparticles due to their unique properties and smaller size offer a plethora of opportunities in the field of medical innovations. Nanotechnology-based therapeutic approaches and their drug delivery potential can essentially help in the diagnosis and therapy of virus-related infections. In the present chapter, we provide an overview of virus-related infections and nanotechnology-based solutions for the detection, drug delivery, and treatment of virus infections have been discussed.

Keywords

Nanotechnology; Nanomaterials; Virus; Diagnosis; Drug delivery; Treatment

Outline

1Introduction

2Diversity in viral infections

3Nanoweapons against viral crusaders

3.1Detection of viruses through novel nanosystems

3.2Nanoparticles as efficient drug delivery vehicles

4Challenges ahead

5Overcoming challenges

6Conclusions

Acknowledgments

References

Further reading

Acknowledgments

Mahendra Rai is thankful to the Polish National Agency for Academic Exchange (NAWA) for financial support (Project No. PPN/ULM/2019/1/00117/A/DRAFT/00001) to visit the Department of Microbiology, Nicolaus Copernicus University, Toruń, Poland.

1: Introduction

Nanotechnology can be defined as the synthesis, creation, and characterization of materials at the nanoscale level. Most of the accounts of nanotechnology in history date back to the classic talk of Richard Feynman in 1959 at the California Institute of Technology, There’s plenty of room at the bottom in which he introduced the idea of building objects from the bottom-up approach (de Morais, Martins, Steffens, Pranke, & de Costa, 2014). However, his ideas did not receive much attention until the 1980s when Eric Drexler published his book Engines of Creation in 1986 in which he envisioned the promises and potentials of nanotechnology in the future. The National Nanotechnology Initiative (NNI) defines nanotechnology as the synthesis and development of atoms, molecules, and macromolecules in the range of 1–100 nm (de Morais et al., 2014). This leads to the development of new products with unique physical, chemical, and mechanical properties. Nanotechnology since its introduction has gained tremendous attention due to its enhanced physicochemical properties offering a wide array of applications in different fields of science and technology (Saravanan et al., 2021).

Nanoparticles are particles in the range of 1–100 nm and differ significantly from other macromolecules due to their high surface area to volume ratio (Rai, Yadav, & Gade, 2009). This factor enhances the overall reactivity, strength, and electrical and mechanical properties of the nanoparticles. Nanomaterials depict applications in an array of fields like medicine, therapeutics, textiles, cosmetics, food industry, packaging, agriculture, and technology (Salata, 2004). Viruses are composed of either DNA or RNA that are enclosed by structural proteins, ubiquitously distributed in nature, and highly contagious. According to the World Health Organization (WHO), the global burden of viral infections is increasing (Nasrollahzadeh, Sajjadi, Soufi, Iravani, & Varma, 2020). Some of the prevalent viral infections in humans caused due to RNA viruses include Hepatitis C, common cold, flu, influenza, measles, polio, SARS, MERS, and COVID-19 (Nasrollahzadeh et al., 2020; Sahu, Sreepadmanabh, Rai, & Chande, 2021).

Coronavirus belongs to the Coronaviridae family; coronavirus and infections caused by them have been reported in livestock animals like pigs, horses, cats, dogs, birds, and bats. In humans, coronavirus infection occurs in the form of common cold and severe respiratory infections like SARS, MERS, and COVID-19 (Nikaeen, Abbaszadeh, & Yousefinejad, 2020). The coronavirus family includes four structural proteins: spike surface glycoprotein, matrix protein, small envelope protein, and nucleocapsid protein. The spike protein in the studies has been found to be responsible for the infectivity of the virus (Raja et al., 2021). A novel coronavirus denoted as COVID-19 emerged in December 2019, in Wuhan, China. It was termed as global pandemic by WHO spreading across 185 countries in the world with very high infection rate and millions of death. The lack of drug and treatment options for COVID-19 increased its fatality rate (Weiss et al., 2020). The development of antiviral therapies is an increasing concern to fight COVID-19 as it shows rapid transmission and a higher risk of a pandemic. The COVID-19 variant first identified in December 2019, showed mutations and developed a new variant in many countries that was more communicable (Raja et al., 2021). Early reports suggest that mutations in spike protein were observed in the new variant making it more transmissible among the population. Alternations in the spike protein make the virus more dreadful and contagious (Singh et al., 2021). Nanotechnology offers the efficient capability to deal with a wide range of health problems including respiratory infections. Nanomaterials can be used to design diagnostic tools for the detection of SARS-CoV-2 and disinfection kits for medical and health-care professionals (Rai et al., 2020; Rai, Bonde, Yadav, et al., 2021; Weiss et al., 2020). Nanoparticles also possess therapeutic potential and can be used in drug delivery applications. Nano-based solutions can be used for the diagnosis, monitoring, therapeutics, and development of vaccines against COVID-19. Early detection of the SARS-CoV-2 virus and controlled and targeted release of antiviral drugs can efficiently inhibit viral replication. In this chapter, we provide an overview of the nanotechnology-based approaches for the detection, delivery, and treatment of viral infections with an emphasis on COVID-19.

2: Diversity in viral infections

Viruses specifically RNA viruses pose the capacity to mutate so rapidly that their infectivity and spreadability increase many folds (Vahedifard & Chakravarthy, 2021). Since ancient times, the emergence and reemergence of deadly viral infections have considerably affected human health despite tremendous progress in medical science and technology. In the last century, the 1918 Spanish influenza  caused by H1N1 influenza virus had caused a global pandemic resulting in a very high mortality rate and infecting one-third of the world’s population. Apart from the influenza virus, human immunodeficiency virus (HIV) has also emerged as a global threat in the past century. Dengue, Ebola, and Zika viruses have also severely affected the global health system. Other virus infections including human papilloma virus (HPV), herpes simplex virus (HSV), and hepatitis also pose a substantial threat to humans (Nasrollahzadeh et al., 2020) (Fig. 1).

Fig. 1

Fig. 1 List of common viruses causing various infections.

The recent outbreak of SARS-CoV-2 has caused pandemic situations across the globe, severely infecting the population of advanced and developing nations with a high mortality rate.

3: Nanoweapons against viral crusaders

Researchers working in the field of nanomedicine have depicted applications of nanoparticles in the detection and tracking of the virus, also the use of nanotechnological tools in drug delivery has been reported. The detection of virus plays a key role in the prevention and elimination of any virus infection (Draz & Shafiee, 2018).

3.1: Detection of viruses through novel nanosystems

Unfortunately, the outbreaks of dengue virus (DENV) every year are a serious cause of concern and harshly affect the health and social system. In this context, Carter, Balaraman, Kucharski, Fraser, and Fraser (2013) developed a novel detection system for the identification of DENV. In this study, the old nanoparticles coupled with DNAzyme (DDZ) activate the salt-induced aggregation of gold nanoparticles (AuNPs) for the detection of dengue virus (DENV). For the study, DNAzyme was designed to identify the 5′ cyclization sequence (5′ CS) preserved in all DENV progeny and conjugated with AuNPs. This conjugated AuNP-DDZ identified the genomic RNA of DENV-2 NGC strain which was used as a model. This detection technique offers low-cost and rapid detection of DENV. In another study, Ahmed, Kang, Oh, Lee, and Neethirajan (2018) proposed a new technique using chiral zirconium quantum dots (Zr QDs) and magnetoplasmonic nanoparticles (MP NPs) for optical detection of SARS-CoV-2. For the study, ZrQDs and MP NPs were conjugated with antibodies (antiinfectious bronchitis virus) of coronavirus. Electrostatic force was used to form binding between IBV specific antibodies and Zr QDs and MP NPS. Antibody-conjugated Zr QDs and MP NPs formed a magnetoplasmonic-fluorescent nanohybrid structure in the presence of the target analyte; while the external magnet separated the nanostructured magnetoplasmonic-fluorescent nanoparticles. Photoluminescence (PL) intensity of nanohybrids was used to measure the concentration of the analyte.

Afsahi et al. (2018) formulated a cost-efficient and portable graphene-enabled biosensor for the detection of the Zika virus. Immobilized monoclonal antibodies were covalently linked to graphene enabling Field Effect Biosensing (FEB) for quantitative detection of Zika virus (ZIKV) antigens. The system showed excellent detection of Zika antigen in human serum. The herpes simplex virus causes life-long viral infections ranging from asymptomatic to severe clinical manifestations.

Chen et al. (2020) developed a rapid and sensitive immunoassay technique for the detection of SARS-CoV-2 in human serum using lanthanide-doped polystyrene nanoparticles (LNPs) (Fig. 2). The LNPs were synthesized using miniemulsion polymerization technique. Further, the LNPS were functionalized with mouse antihuman IgG antibody (MHIgG) and rabbit IgG (RIgG). The mouse antihuman IgG antibody with self-assembled LNPs served as a fluorescent reporter during sample analysis. Recombinant nucleocapsid phosphoprotein of SARS-CoV-2 was dispensed on the nitrocellulose membrane for the assay. The results of the immunoassay achieved positive identification of SARS-CoV-2 in human serum samples.

Fig. 2

Fig. 2 Rapid and sensitive detection of SARS-CoV-2. Reproduced from Chen, Z., Zhang, Z., Zhai, X., Li, Y., Lin, L., Zhao, H., et al. (2020). Rapid and sensitive detection of anti-SARS-CoV-2 IgG, using lanthanide-doped nanoparticles-based lateral flow immunoassay. Analytical Chemistry, 92, 7226–7231. https://pubs.acs.org/doi/10.1021/acs.analchem.0c00784. Permission available via the PMC Open Access Subset for unrestricted RESEARCH reuse and analyses. Further permission related to the material excerpted should be directed to the ACS. Copyright © 2020 American Chemical Society.

The emergence of viral infections forms a global health challenge. Draz, Vasan, Muthupandian, Kanakasabapathy, et al. (2020) designed a nanoparticle-enabled smartphone (NES) system for faster and sensitive detection of viruses. A specially designed platinum nanoparticle probe is labeled on a microchip that captures the virus by inducing gas bubble formation in the presence of hydrogen peroxide. These gas bubbles form distinctive visual patterns paving the way for the detection of the virus through a convolutional neural network (CNN)-enabled smartphone system. This system enables simple and easy detection of hepatitis B virus (HBV), HCV, and Zika virus (ZIKV).

Huang, Wen, Shi, Zeng, and Jiao (2020) designed colloidal gold nanoparticle-based lateral- flow (AuNP-LF) assay or rapid on-site detection of IgM antibody against the SARS-CoV-2 virus using indirect immunochromatography method (Fig. 3). For the study, AuNP-LF strips were prepared by coating SARS-CoV-2 nucleoprotein (SARS-CoV-2 NP) on an analytical membrane to capture the sample, and AUNPS was conjugated with antihuman IgM to detect the reporter. The AuNP-LF assay was optimized through alteration of pH value and amount of antihuman IgM. Experimentation was performed through a thorough evaluation of serum samples of COVID-19 patients and non-COVID individuals. The results obtained were also compared with RT-PCR. The results show that the immunoassay demonstrated excellent efficiency in the detection of IgM against the SARS-CoV-2 virus with a 100% and 93.35% sensitivity, respectively.

Fig. 3

Fig. 3 Rapid and sensitive detection of SARS-CoV-2 using colloidal gold nanoparticle-based lateral-flow (AuNP-LF) assay. Reproduced from Huang, C., Wen, T., Shi, F. J., Zeng, X. Y., & Jiao, Y. J. (2020). Rapid detection of IgM antibodies against the SARS-CoV-2 virus via colloidal gold nanoparticle-based lateral-flow assay. ACS Omega, 5, 12550–12556. https://pubs.acs.org/doi/10.1021/acsomega.0c01554. Permission available under ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for noncommercial purposes. Further permission related to the material excerpted should be directed to the ACS. Copyright © 2020 American Chemical Society.

A colorimetric assay-based naked-eye detection of SARS-CoV-2 using colloidal gold nanoparticles was reported by Moitra, Alafeef, Dighe, Frieman, and Pan (2020). Thiol-modified ASO-capped AuNPs agglomerated selectively toward the target RNA sequence of SARS-CoV-2 and depicted a change in its surface plasmon resonance (Fig. 4). Also, the RNase cleaved the RNA strand from RNA-DNA composite hybrid forming a precipitate that can be visually detected in the solution. The selectivity of the immunoassay technique was also checked for SARS-CoV-2 viral load. The technique offers rapid naked eye detection without the use of any sophisticated instruments.

Fig. 4

Fig. 4 Rapid and naked eye detection of SARS-CoV-2 using colloidal gold nanoparticles. Reproduced from Moitra, P., Alafeef, M., Dighe, K., Frieman, M. B., & Pan, D. (2020). Selective naked eye detection of SARS-CoV-2 mediated by N gene targeted antisense oligonucleotide capped plasmonic nanoparticles. ACS Nano, 14, 7617–7627. https://pubs.acs.org/doi/10.1021/acsnano.0c03822. Permission available via the ACS COVID-19 subset for unrestricted RESEARCH reuse and analyses in any form or by any means with acknowledgment of the original source. Further permission related to the material excerpted should be directed to the ACS. Copyright © 2020 American Chemical Society.

Magnetic nanoparticles have also shown application in the detection of SARS-CoV-2. Zhao et al. (2020) reported the synthesis of poly(amino ester) with carboxyl group (PC)-coated magnetic nanoparticles (pcMNPs) and the use of pcMNPs-based viral RNA extraction method for the detection of novel coronavirus. The pcMNPs-RNA complexes were formed by combining the lysis and binding steps followed by a direct introduction to RT-PCR reactions. This simplification leads to the purification of viral RNA within 20 min without the use of any automated approach. The extraction method identifies two different regions (ORFlab and N gene) of viral RNA generating a linear correlation between 10 and 105 copies of SARSCoV-2 pseudovirus particles. The technique eases the clinical diagnosis of SARS-Cov-2.

A low-cost, rapid, and electrochemical sensor chip-enabled digital detection technique for the detection of SArs-CoV-2 was designed by Alafeef, Dighe, Moitra, and Pan (2020). The biosensor was devised using gold nanoparticles capped with specific single-stranded DNA (ssDNA) antisense oligonucleotides which target viral nucleocapsid phosphoprotein (N-gene) of SARS-CoV-2 (Fig. 5). The biosensor probes were immobilized on a paper-based electrochemical chip with a readout for recording sample signals. The sensing capability of the biosensor was evaluated using SARS-CoV-2-infected samples (22 COVID-19-infected patients and 26 healthy asymptomatic persons) and excellent output signals were obtained within 5 min. The biosensor effectively identified the positive samples with precision.

Fig. 5

Fig. 5 Electrochemical sensing of SARS-CoV-2 using gold nanoparticle-based electrochemical biosensor chip. Reproduced from Alafeef, M., Dighe, K., Moitra, P., & Pan, D. (2020). Rapid, ultrasensitive, and quantitative detection of SARS-CoV-2 using antisense oligonucleotides directed electrochemical biosensor chip. ACS Nano, acsnano0c06392. https://pubs.acs.org/doi/10.1021/acsnano.0c06392 Advance online publication. https://doi.org/10.1021/acsnano.0c06392. Permission available via the PMC Open Access Subset for unrestricted RESEARCH reuse and analyses. Further permission related to the material excerpted should be directed to the ACS. Copyright © 2020 American Chemical Society.

3.2: Nanoparticles as efficient drug delivery vehicles

As far as the delivery of therapeutics is concerned, Paul et al. (2014) enhanced the delivery of small interfering RNAs (siRNAs) by complexing it with AuNPs. The AuNP-siRNA complexes were evaluated for their therapeutic potential in the in vitro studies. It was observed that the cationic complex enters Vero cells and effectively reduces DENV serotype 2 (DENV-2) replication. Moreover, it prevents virion release in both preinfection and postinfection conditions. Thus, the authors concluded that AuNPs can efficiently deliver siRNAs to control in vitro infection of DENV.

Lopinavir (LPV) is a promising HIV protease inhibitor and an essential part of antiretroviral therapy but with poor oral bioavailability. Ritonavir (RTV) is coformulated with LPV to improve its oral bioavailability. Rao, Vats, Dalal, and Murthy (2014) prepared stearic acid-based LPV loaded solid lipid nanoparticles (SLNs) using hot melt emulsion technique. In vitro drug release study depicted biphasic sustained drug release; also increased oral bioavailability of LPV SLNs was observed with better tissue distribution of LPV in HIV reservoirs.

Pawar and Jaganathan (2016) prepared glycol chitosan (GC) nanoparticles to receive systemic and mucosal immune responses against nasally administered hepatitis B surface antigen (HBsAg). The nanoparticles were synthesized with high loading efficiency with an average particle size of 200 nm. In vivo studies were performed to check the immunogenicity of GC NPs; it was observed that GC NPs induce strong humoral and mucosal immunity suggesting a novel system for mucosal delivery of vaccines.

Silver nanoparticles (AgNPs) are known to possess significant antiviral property which has been harnessed by several researchers (Gaikwad, Ingle, Gade, et al., 2013; Rai et al., 2016). For example, Li, Lin, Zhao, Xu, et al. (2016) described the synthesis of AgNPs conjugated with oseltamivir (OTV) to check their antiviral potential against the influenza virus. In a comparative study, it was observed that in comparison with silver and oseltamivir, oseltamivir- modified AgNPs (Ag@OTV) notably inhibited H1N1 infection. Also, Ag@OTV inhibited the activity of neuraminidase (NA) and hemagglutinin (HA) preventing the attachment of the influenza virus to the host cell. It was hypothesized that Ag@OTV blocks influenza virus from infecting MDCK (Madin-Darby canine kidney) cells and prevents DNA fragmentation, chromatin condensation, and activity of caspase-3. Ag@OTV also inhibits the accumulation of reactive oxygen species (ROS) by H1N1 influenza virus.

Acyclovir is used as an antiherpetic drug to treat acute asymptomatic herpes infection. This drug reduces the severity of infection but cannot cure it. Donalisio et al. (2018) developed chitosan nanospheres using the nanoemulsion template method for the delivery of acyclovir. In vitro skin penetration study and biological studies were conducted on the Vero cell line infected by HSV-1 and HSV-2 strains. The in vitro skin penetration studies depicted improved penetration of acyclovir. Also, the acyclovir-NS complex showed higher antiviral activity compared to free acyclovir against HSV-1 and HSV-2 strains.

Hyperinflammation generated due to the cytokine storm in SARS-CoV-2 patients leads to acute respiratory distress syndrome and death which forms a major challenge in the treatment of corona-infected patients. Dormont, Brusini, Cailleau, et al. (2020) developed multidrug nanoparticles for controlling hyperinflammation occurring due to cytokine storms. The multidrug nanoparticles were synthesized using squalene, which is natural lipid, and conjugating with adenosine that acts as an immunomodulator, then α-tocopherol was used for encapsulation. In vivo studies were conducted to check the therapeutic efficiency of the multidrug nanoparticles, the animal model studies showed an improvement in survival rate after injection with multidrug nanoparticles. Further studies are needed to strongly support the hypothesis of the use of multidrug nanoparticles.

He, Lin, Wang, et al. (2020) reported a novel vaccine strategy for SARS-CoV-2 by combining antigen optimization and protein nanoparticles. For the study, the authors designed a receptor-binding domain (RBD)-specific antibody column to enable tag-free purification, it was then hypothesized that using the SpyTag/SpyCatcher system self-assembling protein nanoparticles (SApNPs) could be conjugated on RBD. Thus, the authors demonstrated the use of SPY system for the advancement of RBD-based SApNP vaccines.

4: Challenges ahead

The global pandemic scenario arising due to the COVID-19 situation has alarmed researchers throughout the world to search for novel technologies that could provide faster detection and diagnostics to identify any infection. The use of nanotechnological protocols has shown great promise regarding the use of nanomaterials in the detection and diagnostics of several virus-related infections. However, there are some challenges that need to be addressed before employing nanotechnology as an innovative technology to treat virus infections. Toxicity issues related to the frequent use of nanoparticle system are a major cause of concern while employing nanoparticles for therapeutic or diagnostic applications. The smaller particle size, shape of nanoparticles, and surface charge also contribute to its cytotoxicity as smaller size nanoparticles can easily enter and interact with cellular components. This interaction of nanoparticles with cellular components also leads to their deposition in various cells leading to tissue damage.

The development of several systems for the detection of viruses has been witnessed but still detection of false-positive cases is high, which is a growing cause of concern. The in vivo tracking of drugs/vaccines still needs a lot of study and refinement. The patient’s acceptance regarding the treatment involving nanotherapeutics is also a cause of concern. Also, higher use of nanomaterials in products will raise environmental concerns, hence searching and developing protocols and systems that are nontoxic and environmentally friendly will be a challenge. Improving the stability and efficiency of nanomaterials for the detection and monitoring of viruses also needs to be considered.

5: Overcoming challenges

Nanoparticle-based systems provide multiple opportunities to overcome the shortcomings of traditional antiviral therapies. Traditional antiviral therapies depict challenges like poor bioavailability and low aqueous solubility. Incorporating nanotechnological applications to traditional drug therapy result in enhanced bioavailability of drugs, reduced drug doses, and targeted delivery. Also, nanoparticles due to their smaller size can cross the biological barrier and ensure targeted delivery at virus reservoir sites. Controlled release and delivery of drugs with the help of nanoparticles reduces the risk of patient’s acceptance to therapy and also protects the recurrence of viral infection during the treatment period. Thus, nanoparticulate systems form novel systems for the delivery of therapeutic drugs and vaccines.

6: Conclusions

Viruses are infectious agents that are responsible for several deaths across the globe for centuries. Lack of availability of efficient clinical drugs for the majority of viral infections emphasizes the need for the development of detection and diagnostic systems for early and rapid identification of viral infection. Significant research needs to be conducted regarding the delivery of drugs and vaccines and their accurate tracking. With the outbreak of SARS-CoV-2 a serious challenge to public health has been raised globally; it has become imperative to develop nano-innovated products and also bring in use green nanomaterials which are nontoxic and environmentally friendly. Thus, considering the present world scenario and time and again reemergence of different viral infections, utilization of nano-based technologies in clinical diagnosis can play a pivotal role in solving these critical issues.

References

Afsahi et al., 2018 Afsahi S., Lerner M.B., Goldstein J.M., Lee J., Tang X., Bagarozzi Jr. D.A. Novel graphene-based biosensor for early detection of Zika virus infection. Biosensors & Bioelectronics. 2018;15(100):85–88. doi:10.1016/j.bios.2017.08.051.

Ahmed, Kang, Oh, Lee and Neethirajan, 2018 Ahmed S.R., Kang S.W., Oh S., Lee J., Neethirajan S. Chiral zirconium quantum dots: A new class of nanocrystals for optical detection of coronavirus. Heliyon. 2018;4:e00962doi:10.1016/j.heliyon.2018.e00766.

Alafeef, Dighe, Moitra and Pan, 2020 Alafeef M., Dighe K., Moitra P., Pan D. Rapid, ultrasensitive, and quantitative detection of SARS-CoV-2 using antisense oligonucleotides directed electrochemical biosensor chip. ACS Nano. 2020;acsnano0c06392. Advance online publication https://doi.org/10.1021/acsnano.0c06392.

Carter, Balaraman, Kucharski, Fraser and Fraser, 2013 Carter J.R., Balaraman V., Kucharski C.A., Fraser T.S., Fraser M.J. A novel dengue virus detection method that couples DNAzyme and gold nanoparticle approaches. Virology Journal. 2013;10:201. doi:10.1186/1743-422X-10-201. 23809208 PMC3765938.

Chen et al., 2020 Chen Z., Zhang Z., Zhai X., Li Y., Lin L., Zhao H. Rapid and sensitive detection of anti-SARS-CoV-2 IgG, using lanthanide-doped nanoparticles-based lateral flow immunoassay. Analytical Chemistry. 2020;92:7226–7231. doi:10.1021/acs.analchem.0c00784.

de Morais, Martins, Steffens, Pranke and de Costa, 2014 de Morais M.G., Martins V.G., Steffens D., Pranke P., de Costa J.A.V. Biological applications of nanobiotechnology. Journal of Nanoscience and Nanotechnology. 2014;14:1007–1914.

Donalisio et al., 2018 Donalisio M., Leone F., Civra A., Spagnolo R., Ozer O., Lembo D. Acyclovir-loaded chitosan nanospheres from nano-emulsion templating for the topical treatment of herpesviruses infections. Pharmaceutics. 2018;10(2):46.

Dormont, Brusini, Cailleau, et al., 2020 Dormont F., Brusini R., Cailleau C. Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation in rodents. Science Advances. 2020;6(23):eaaz5466.

Draz and Shafiee, 2018 Draz M.S., Shafiee H. Applications of gold nanoparticles in virus detection. Theranostics. 2018;8(7):1985–2017. doi:10.7150/thno.23856.

Draz, Vasan, Muthupandian, Kanakasabapathy, et al., 2020 Draz M.S., Vasan A., Muthupandian A., Kanakasabapathy M.K. Virus detection using nanoparticles and deep neural-network-enabled smart phone system. Science Advances. 2020;6:eabd5354.

Gaikwad, Ingle, Gade, et al., 2013 Gaikwad S., Ingle A., Gade A. Antiviral activity of mycosynthesized silver nanoparticles against herpes simplex virus and human parainfluenza virus type 3. International Journal of Nanomedicine. 2013;8:4303–4314.

He, Lin, Wang, et al., 2020 He L., Lin X., Wang Y. Self-assembling nanoparticles presenting receptor binding domain and stabilized spike as next-generation COVID-19 vaccines. BioRxiv. 2020;doi:10.1101/2020.09.14.296715.

Huang, Wen, Shi, Zeng and Jiao, 2020 Huang C., Wen T., Shi F.J., Zeng X.Y., Jiao Y.J. Rapid detection of IgM antibodies against the SARS-CoV-2 virus via colloidal gold nanoparticle-based lateral-flow assay. ACS Omega. 2020;5:12550–12556. doi:10.1021/acsomega.0c01554.

Li, Lin, Zhao, Xu, et al., 2016 Li Y., Lin Z., Zhao M., Xu T. Silver nanoparticle based co-delivery of oseltamivir to inhibit the activity of the H1N1 influenza virus through ROS-mediated signaling pathways. ACS Applied Materials and Interfaces. 2016;8(37):24385–24393.

Moitra, Alafeef, Dighe, Frieman and Pan, 2020 Moitra P., Alafeef M., Dighe K., Frieman M.B., Pan D. Selective naked eye detection of SARS-CoV-2 mediated by N gene targeted antisense oligonucleotide capped plasmonic nanoparticles. ACS Nano. 2020;14:7617–7627.

Nasrollahzadeh, Sajjadi, Soufi, Iravani and Varma, 2020 Nasrollahzadeh M., Sajjadi M., Soufi G.J., Iravani S., Varma R.S. Nanomaterials and nanotechnology-associated innovations against viral infections with a focus on coronaviruses. Nanomaterials (Basel Switzerland). 2020;10(6):1072.

Nikaeen, Abbaszadeh and Yousefinejad, 2020 Nikaeen G., Abbaszadeh S., Yousefinejad S. Application of nanomaterials in treatment, anti-infection and detection of coronaviruses. Nanomedicine. 2020;15(15):1501–1512.

Paul et al., 2014 Paul A.M., Shi Y., Acharya D., Douglas J.R., Cooley A., Anderson J.F. Delivery of antiviral small interfering RNA with gold nanoparticles inhibits dengue virus infection in vitro. The Journal of General Virology. 2014;95(Pt 8):1712–1722. doi:10.1099/vir.0.066084-0.

Pawar and Jaganathan, 2016 Pawar D., Jaganathan K.S. Mucoadhesive glycol chitosan nanoparticles for intranasal delivery of hepatitis B vaccine: Enhancement of mucosal and systemic immune response. Drug Delivery. 2016;23(1):185–194. doi:10.3109/10717544.2014.908427.

Rai et al., 2020 Rai M., Bonde S., Yadav A., Plekhanova Y., Reshetilov A., Gupta I. Nanotechnology-based promising strategies for the management of COVID-19: Current development and constraints. Expert Review of Anti-Infective Therapy. 2020;8:1–10. doi:10.1080/14787210.2021.1836961. (Epub ahead of print) 33164589.

Rai, Bonde, Yadav, et al., 2021 Rai M., Bonde S., Yadav A. Nanotechnology as a shield against COVID-19: Current advancement and limitations. Viruses. 2021;13(7):1224. (Published 2021 Jun 24) https://doi.org/10.3390/v13071224.

Rai et al., 2016 Rai M., Deshmukh S., Ingle A., Gupta I., Galdiero S., Galdiero M. Metal nanoparticles: The protective nanoshield against virus infection. Critical Reviews in Microbiology. 2016;42(1):46–56.

Rai, Yadav and Gade, 2009 Rai M., Yadav A., Gade A. Silver nanoparticles as a new generation of antimicrobials. Biotechnology Advances. 2009;27(1):76–83.

Raja et al., 2021 Raja R.K., Nguyen-Tri P., Balasubramani G., Alagarsamy A., Hazir S., Ladhari S. SARS-CoV-2 and its new variants: A comprehensive review on nanotechnological application insights into potential approaches. Applied Nanoscience. 2021;doi:10.1007/s13204-021-01900-w.

Rao, Vats, Dalal and Murthy, 2014 Rao P.R., Vats R., Dalal V., Murthy A.N. A hybrid design to optimize preparation of lopinavir loaded solid lipid nanoparticles and comparative pharmacokinetic evaluation with marketed lopinavir/ritonavir coformulation. Journal of Pharmacy and Pharmacology. 2014;66(7):912–926. doi:10.1111/jphp.12217.

Sahu, Sreepadmanabh, Rai and Chande, 2021 Sahu A.K., Sreepadmanabh M., Rai M., Chande A. SARS-CoV-2: Phylogenetic origins, pathogenesis, modes of transmission, and the potential role of nanotechnology. Virus Disease. 2021;32:1–12. doi:10.1007/s13337-021-00653-y.

Salata, 2004 Salata O. Applications of nanoparticles in biology and medicine. Journal of Nanbiotechnology. 2004;2:3.

Saravanan et al., 2021 Saravanan M., Mostafavi E., Vincent S., Negash H., Andavar R., Perumal V. Nanotechnology-based approaches for emerging and re-emerging viruses: Special emphasis on COVID-19. Microbial Pathogenesis. 2021;156:104908. doi:10.1016/j.micpath.2021.104908.

Singh et al., 2021 Singh Y.D., Ningthoujam R., Panda M.K., Jena B., Babu P.J., Mishra A.K. Insight from nanomaterials and nanotechnology towards COVID-19. Sensors International. 2021;2:100099.

Vahedifard and Chakravarthy, 2021 Vahedifard F., Chakravarthy K. Nanomedicine for COVID-19: The role of nanotechnology in the treatment and diagnosis of COVID-19. Emergent Materials. 2021;4:75–99.

Weiss et al., 2020 Weiss C., Carriere M., Fusco L., Capua I., Regla-Nava J.A., Pasquali M. Toward nanotechnology-enabled approaches against the COVID-19 pandemic. ACS Nano. 2020;14(6):6383–6406.

Zhao et al., 2020 Zhao Z., Cui H., Song W., Ru X., Zhou W., Yu X. A simple magnetic nanoparticles-based viral RNA extraction method for efficient detection of SARS-CoV-2. BioRxiv. 2020;doi:10.1101/2020.02.22.961268.

Further reading

Gupta R., Sagar P., Priyadarshi N., Kaul S., Sandhir R., Rishi V. Nanotechnology based approaches for the detection of SARS-CoV-2. Frontiers in Nanotechnology. 2020;2:589832.

Hu T.Y., Frieman M., Wolfram J. Insights from nanomedicine into chloroquine efficacy against COVID-19. Nature Nanotechnology. 2020;15(4):247–249. doi:10.1038/s41565-020-0674-9.

Milane L., Amiji M. Clinical approval of nanotechnology-based SARS-CoV-2 mRNA vaccines: Impact on translational nanomedicine. Drug Delivery and Translational Research. 2021;11:1309–1315. doi:10.1007/s13346-021-00911-y.

Chapter 2: Nanotechnology-based innovations to fight against viral infections

Tazib Rahaman Syed    Institut National de la Recherche Scientifique, EMT Research Center, Varennes, QC, Canada

Abstract

The coronavirus disease pandemic 2019 (COVID-19) caused by the severe acute respiratory coronavirus 2 syndrome (SARS-CoV-2) has posed an unprecedented challenge to health-care systems in nearly every country around the world. There are currently no proven effective vaccines or therapeutic agents against the virus. Current clinical management includes measures to prevent and control infections, as well as supportive care including additional oxygen and mechanical ventilation support. The provision of accurate information to both physicians and patients is important because of the present SARS-CoV-2 (COVID-19) condition. Thus, there is an alarming need to discuss novel treatment strategies for the treatment of such viral outbreaks. Viral diseases have reportedly affected millions of people around the world, with a major effect on human health and socioeconomic development. This analysis examines different nanocarriers (e.g., liposomes, polymeric nanoparticles, solid lipid nanoparticles, etc.) which are completely based on methods implemented in the literature and in the clinic to address the numerous challenges faced by antiviral therapy. This chapter includes a recent strategy devised using nanomedicine to treat the H1N1 Influenza virus. In this chapter, we have also tried to discuss a few viruses which help in cancer therapy including recent developments in the treatment of COVID-19 using nanotechnology.

Keywords

COVID-19; H1N1; Nanomedicine; HIV; SARS

Outline

1Introduction

2Types of nanocarriers

2.1Liposomes

2.2Polymer-based nanoparticles

2.3Dendrimers

2.4Solid lipid nanoparticles

2.5Nanosuspensions

2.6Nanoemulsions

3Nanomedicine and COVID-19

4Viruses as nanocarriers

5Viruses used in the treatment of cancer

6ZnO nanoparticles used in treatment of the H1N1 influenza virus

7Nanomedicine as a diagnostic agent of hepatitis C virus

8Conclusions

References

Further reading

Conflicts of interest

The author declares no conflicts of interest.

1: Introduction

Emerging infectious diseases are one of the 21st-century’s most significant public health challenges. These include zoonotic viruses that originated from species of reservoirs, often mammals, and that jump to humans to cause disease syndromes of varying shape and severity. An emerging virus could lead to individual or a few sporadic cases depending on its ability to transmit among humans, resulting in a localized outbreak requiring public health intervention or, in the worst scenarios, may develop into a large epidemic or global pandemic. Such emerging events are numerous and varied in the last two decades. These include unfamiliar viruses, such as SARS and MERS coronaviruses, and familiar enemies that have reappeared to cause outbreaks, such as swine and avian influenza, and Ebola and Zika viruses.

Not only global health services but also socioeconomic growth gets affected by viral diseases. Many serious diseases such as Hepatitis B and C, Acquired immunodeficiency syndrome (AIDS), COVID-19, H1N1 influenza, Avian influenza, H5N1 influenza, and severe acute respiratory syndrome (SARS) were caused by viruses (Fig. 1). Vaccination is an economic and effective way to combat viral diseases (Koff & Fidler, 1985). Vaccines against major viral diseases such as HIV and hepatitis C virus (HCV) were reportedly still in their infancy and would have limited potential for success: millions are currently infected with these viruses. In view of the vaccine problems, rational drug use seems to be the perfect method for controlling viral diseases. Viral infections pose major challenges to global health, particularly in view of the ongoing decline in the use of successful antiviral therapies as a result of viral strain resistance and adverse effects associated with extended antiviral usage (Immordino, Dosio, & Cattel, 2006). The need for safe and effective alternatives to traditional antivirals is therefore imperative (Fig. 2).

Fig. 1

Fig. 1 The enormous rise in the rate of COVID-19 infection when compared with that of other global pandemics. Source: Wikipedia.com.

Fig. 2

Fig. 2 Depicts the importance of the use of nanomaterials for diagnosis and treatment of viral infection such as COVID-19. Gold nanoparticles are reportedly said to be essential for the diagnosis of COVID-19 ( Lew et al., 2021). Created with BioRander.com.

Due to the origin of nanotechnology and the availability of a variety of nanocarriers for drug delivery, it is possible to achieve wider fractional distribution of different therapeutic agents at the target site and marginal delivery to the body’s nontarget location (Lembo & Cavalli, 2010). In antiviral medicine supplies, nanotechnology is gaining prominence and is the subject of contemporary science. Researchers had been successful in developing various nanoparticles, including liposomes, dendrimers, polymeric nanoparticles, solid lipid nanoparticles, inorganic nanoparticles (e.g., zinc oxide, gold, silver), and nanoemulsion, chitosan nanoparticles, and neosomes, for use in current antiviral therapies (Gilbert & Knight, 1996).

All the abovementioned types of nanocarriers were of submicron size but varied in their physicochemical properties, biological behavior, and methods of manufacture. Here are some of the well-recognized advantages of nanocarriers that make them ideal candidates for antiviral drug delivery: (1) Poor water solubility and toxic drugs could be hosted within the nanocarrier to achieve enhanced stability and solubility under physiological conditions. (2) Phagocytotic cells, which were considered to be the principal viral reservoirs, can quickly absorb nanocarriers. (3) Increasing the bioavailability of encapsulated active substances by nanocarriers. (4) The nanocarriers provide microbicidal gels with mucoadhesiveness. (5) Nanocarriers deliver the drug intracellularly. (6) Nanocarriers can reduce antiviral drug toxicity and enhance clinical compliance and delay resistance. (7) Because of their nanometric size, nanocarriers could reportedly cross biological barriers, such as the blood-brain barrier (BBB). (8) Nanocarriers could increase cellular absorption, tissue tolerance, and transportation, thereby allowing effective delivery to the target site. (9) Sustainable release of nanocarriers is always