Journal of Current Biomedical Reports jcbior.com Volume 2, Number 2, 2021 eISSN: 2717-1906 1 Review Use of nanotechnology in the diagnosis and treatment of coronavirus Elham Maghareh Abed1, Seyedeh Mahsan Hoseini-Alfatemi2, Hoda Sabati3, Mohammad Amin Khajavi Gaskarei4, Kourosh Delpasand4, Marzie Ghasemi5,* 1Department of Microbiology, Faculty of Biological Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran 2Pediatric Infections Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3Biotechnology and Biological Science Research Center, Shahid Chamran University of Ahvaz, Ahvaz, Iran 4Razi Clinical Research Development Unit, Guilan University of Medical Sciences, Rasht, Iran 5Department of Biochemistry, School of Medicine, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran Abstract Coronavirus is a beta virus that has caused a worldwide pandemic since December 2019. Many treatments such as antiviral drugs, immunosuppressive drugs, neutralizing antibodies, and monoclonal antibodies have been tested on coronavirus disease 2019 (COVID-19) that most of them were effective. Given that nanotechnology-based approaches have been successful in detection and treatment of viral systems such as human immunodeficiency virus (HIV), influenza A virus subtype H1N1 and Middle East respiratory syndrome coronavirus (MERS-CoV), they also seem to be effective in detecting and treating COVID-19. Nanotechnology is used in various methods for early and rapid diagnosis of the disease. Nanoparticles can be used in products for the diagnosis, treatment and prevention of COVID- 19. These substances are very effective in the controlled delivery of antiviral drugs and biomolecules and they are also used in the manufacture of personal safety equipment, widely, and the production of anti-virus coatings for surfaces, air filters and the production of vaccines. In general, nanomaterial can play an important role in controlling the disease, based on strategies to prevent the virus from entering the host cell, inhibiting virus replication, virus delivery systems, and nano-based vaccines. Nanotechnology is a multidisciplinary tool that can offer a variety of solutions based on disease prevention, diagnosis and treatment strategies. Keywords: COVID-19, Nanotechnology, Coronavirus, Diagnosis, Treatment 1. Introduction The corona pandemic that has occurred in the world since the last days of 2019 is related to a virus called coronavirus-2019 (COVID-19) and belongs to the beta virus family along with Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus * Corresponding author: Marzie Ghasemi, MSc Department of Biochemistry, School of Medicine, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran Tel/Fax: +98 933 6357377 Email: marzieghasemi1985@gmail.com https://orcid.org/0000-0001-6753-8356 Received: February, 21, 2021 Accepted:, March, 13, 2021 (MERS-CoV) [1]. This virus has a single-stranded positive RNA genome [2]. The virus attaches to the human angiotensin converting enzyme-2 (ACE-2) and binds to the host cell. This enzyme is a receptor for the SARS-CoV-2 virus in the host cell [3]. They cause several diseases in humans and animals, including © The Author(s) 2021 https://jcbior.com/ Maghareh Abed et al. 2 respiratory, intestinal, hepatic, and nervous systems [4]. The rate of human-to-human transmission of coronavirus is significantly high and causes a wide range of clinical manifestations in patients infected with the virus [5]. However, the reproductive number and transmission way are not yet completely understood, the routes of transmission with and without symptoms and the role of environmental factors should be better known. Widespread geographical epidemics and prevalence in large populations of the world, rapid transmission, recurrent infections and genomic alteration [6, 7], create difficult barriers to the development of ways to prevent, control, and treat this disease [8, 9]. A wide range of possible treatments is being tested. Based on the SARS-CoV-2 life cycle and its structure, the treatments proposed for Covid-19 have been antiviral drugs, immunosuppressive drugs, neutralizing and monoclonal antibodies [10], and vaccines. Antiviral drugs effect by inhibiting ribonucleic acid (RNA) polymerase, viral protease, membrane occlusion, and widespread of antiviral effects [10]. Currently, oxygen therapy and the use of the respiratory tract play a major role in the treatment of COVID-19 [11]. Recent clinical results for antiviral drugs have not been very satisfactory [12]. Some drugs have also been suggested to reduce the damage caused by SARS-CoV- 2 to the lungs [8]. In some cases, plasma therapy is also suggested [13]. This method of treatment is used in patients who are not able to produce enough antibodies and is a safe and effective method and seems to reduce mortality [14]. Scientists believe nanotechnology-based approaches could help against covid-19. Based on previous studies, nanotechnology can be effective in identifying viral systems and overcome the limitations of conventional methods of viral disease strategies [15, 16]. In this study, in addition to reviewing the effects of nanotechnology in the fight against other viral diseases, the proposed nanotechnology-based solutions in the diagnosis, treatment, and prevention of environmental pollution caused by covid-19 are examined. 2. Application of nanotechnology in the detection and treatment of viral infections According to previous research, nanotechnology has been considered in the process of diagnosis and treatment of many viral diseases. The use of luminescence electrochemical biosensors for the selective detection of avian influenza virus (H9N2- AIV) [17] and the use of magnetic nanoparticles (NPs) for the detection of influenza A virus subtype H1N1 virus [18] are examples of nanoparticles applications in virus detection. The use of poly vinyl pyrrolidone (PVP) coated AgNPs (30-50 nm) on HIV strains has also been shown to have antiviral activity [19]. Curcumin nanoparticles also have high antiviral properties against the respiratory syncytial virus (RSV) [20]. Dendrimers have also been extensively studied for human immunodeficiency virus (HIV) disinfection applications. These nanoparticles suppress virus replication [21]. Lipid-based nanoparticles have previously been tested for the treatment of HIV, herpes, hepatitis B (HBV), and hepatitis C (HCV) viruses. These nanoparticles can encapsulate different classes of antiviral drugs and are a mediator of drug delivery to the target tissue or cell, as well as modulating specific biological responses [22]. Aluminum nanoparticles are another class of metal structures that can be used in vaccines for respiratory viruses such as MERS-CoV and SARS- CoV-2. These compounds elicit cellular and humoral immunity responses [23]. Unsaturated liposomes also have an inhibitory effect against HBV, HCV, and HIV [22]. 3. SARS-CoV-2 and nanotechnology insights Nanotechnology-based treatment strategies are a promising way to overcome the current limitations in the prevention, diagnosis, and treatment of Covid-19 [24]. Nanomaterials can be used for disease diagnosis to develop simpler, cheaper, and faster methods. In therapy, nanosystems can be used in the controlled delivery of antiviral drugs and biomolecules to the lungs and target tissues that are used to prevent virus replication or inactivation of viral particles [25]. There are successful prospects in building safe personal protective equipment [25] and producing vaccines or immune modulators using nanotechnology [16]. Maghareh Abed et al. 3 4. Detection of SARS-CoV-2 with nanotechnology Currently, the only way to diagnose Covid-19 infection is to test for nucleic acid by reverse transcription polymerase chain reaction (RT-PCR). But this method also has limitations; it is not able to diagnose asymptomatic patients, not all health care centers, especially in non-urban environments, are equipped with sufficient PCR infrastructure. While accurate and early diagnosis of the disease is a vital requirement for essential care. Nanotechnology can meet these demands through nucleic acid testing methods, point-of-care testing (POCT), electrochemical sensors, and biosensors [15]. In the nucleic acid test method, the nucleic acid is amplified in nucleic acid isothermal conditions. This method is very sensitive, rapid, and specific [26]. Nanomaterials exhibit electrical and optical properties that have been extensively applied in the development of diagnostic methods such as point-of-care testing (POCT) biosensors. These substances can improve the sensitivity of diagnosis, rapid isolation of patients, and facilitate the treatment process [24]. Different types of nanomaterials include; nanoparticles, nanoclusters, quantum dots, carbon nanotubes, nanocomposites, etc that have been used to increase the performance of biosensors. Recently, deoxyribonucleic acid (DNA) sensor nanomaterials have been developed for simple, rapid, selective, low-cost, and sensitive detection of infectious diseases [27]. Biosensors are color-coded test points that can detect contaminated specimens through simple color changes that are visible to the naked eye [15]. A sample of these POCTs has been generated using gold nanoparticles to detect the MERS-CoV virus [28]. In another method, reverse transcription Loop-Mediated Isothermal Amplification (RT-LAMP) with nano-based biosensors has been used to detect COVID-19 [29]. Electrochemical sensors are effective in detecting viruses due to their high sensitivity and the possibility of shrinkage. Gold nanoparticles (AuNPs) are one of the most attractive nanomaterials because they have electronic optical properties that can be detected by a variety of biosensors, especially those based on colorimetric, electrochemical [30]. The use of AuNPs in these sensors is much more effective in detecting viruses by immobilizing biomolecules while maintaining their function [31]. 5. Treatment of SARS-CoV-2 with nanotechnology The specific antiviral drug for SARS-CoV-2 is not currently available to the public [32]. Production of these drugs is a time-consuming process that must be monitored and tested for safety before use [33]. On the other hand, increasing virus resistance is another limitation of the production and use of antiviral drugs [15]. In some studies, nanotechnology has been widely applied in the treatment of this disease. Nanotechnology through methods such as; preventing viruses from entering host cells, inhibiting virus replication, virus transmission systems, and nano- based vaccines is probably successful in treating the disease [15]. Also, many of the proposed treatments for covid- 19 infection that are spreading, use nano-based methods such as; SARS-CoV-2 virus-like particles by using iBio's Fast Pharming technology[15]. Nanoparticles (NP) (organic and inorganic) have been considered for some of their properties. Inorganic NPs (INPs) have properties such as luminescence, adjustable size, shape, composition, high surface-to-volume ratio, and the ability to expose multiple reciprocal locations on the surface. The most common types of INPs are mesoporous silica NPs, iron oxide NPs and metal NPs (gold, silver). Organic NPs include; Carbon nanotubes and graphene nanoparticles are polymeric and lipid NPs, dendrimers, extracellular vesicles (or exosomes), liposomes, and nanomolecules. Organic nanoparticles are being noticed because of their potential site- specific targeting, drug release control, biodegradation, biocompatibility, and non-toxicity [34]. 6. Pharmacological treatment The first step in starting a viral infection is the virus's attachment to the host. Nanoparticles have the ability to prevent the virus from adherent to the host cell and entering the cell [35]. One way to use nanoparticles to prevent the virus from entering the host cell is to use carbon quantum dots that if combined with boronic acid show stronger antiviral activity [36]. The use of gold nano rods in antiviral therapy for MERS has also been successful [37]. Maghareh Abed et al. 4 Second, if the virus enters the host cell, the spread of infection can be prevented with nanoparticles, mainly as carriers for the delivery of antiviral molecules. Higher specificity, improvement of drug solubility, the combination of different drug molecules in one particle, and reduction of toxicity for the host are the advantages of nanoparticles in this field [15]. Some nanoparticles, such as Ag2S nanoclusters, can prevent the virus from replicating in the host body. These nanoparticles also play a role in enhancing the expression of pro-inflammatory cytokines, which are effective against viral infections [38]. Zinc oxide (ZnO) nanoparticles have similar activity and effective against H1N1 influenza virus infection [39] and it also seems to be involved in inhibiting the proliferation of SARS-CoV-2 [40]. Traditional methods of prescribing antiviral drugs have limitations such as poor bioavailability, systemic toxicity, susceptibility to in vivo destruction, and short half-life. In contrast, nanotechnology drugs have advantages such as higher bioavailability, lower toxicity, protection against degradation, improved circulating half-life, reduced effective dose of the drug, the ability to cross biological barriers [41], and tissue or cellular targeting [42]. Also, nanocarriers provide the ability to control drug release in the target tissue, improve biocompatibility and reduce drug toxicity in healthy tissues by confining drugs [24]. Nano compounds such as micelles, microspheres, liposomes, and dendrimers have been used for better and targeted delivery of antiviral drugs such as efavirenz, zidovudine, and acyclovir [42]. 7. Prevention of SARS-CoV-2 with nanotechnology 7.1 Improving personal protective equipment (PPE) using nanotechnology In cases where a definitive cure for COVID-19 has not yet been discovered, prevention is especially important in vulnerable people such as the elderly, those with immunodeficiency, and at-risk individuals include healthcare professionals [43]. Although observing physical distance is known as the first step but, it is difficult to implement in the healthcare staff. Therefore, equipping these people with highly efficient safety and PPE is a very necessary step [15]. 7.2 Environmental, surface disinfectants, and healthcare Studies have shown that the SARS-CoV-2 virus remains on the surface for a long time [44, 45], so even the PPE kits used may be infected with the virus [46]. Therefore, the production of anti-virus coatings on surfaces and air filtration devices can help reduce infection. Nanomaterials have the ability to prevent viral contamination by air and contact with contaminated surfaces and have the ability to sterilize protective equipment, especially in hospital settings [24]. Creating self-disinfecting surfaces is another strategy to prevent the spread of COVID-19. Coating surfaces using nanomaterials such as silver, zinc oxide, and copper NPs is one of these solutions. These compounds oxidize and release ions with antimicrobial properties [25, 47]. According to studies, controlled and long-term diffusion of ions in some metals, such as copper, modulates the antiviral properties of surfaces [48]. These nanoparticles are loaded into a polymer matrix and provide an effective antiviral coating on surfaces [15]. This method can also be applied to polypropylene masks. This method has already been used in the preparation of protective masks against influenza viruses. This was done by depositing a coating of silver or silica nanocoating composite on face masks [49]. Graphene in face masks can also sterilize these and allow them to be reused [50]. This coating is also suitable for use on surfaces in public places [51]. There are several products made of nanocomposites that have antimicrobial activity and are used in the disinfection of surfaces. CAC-717 is a new disinfectant consisting of calcium hydrogen carbonate mesoscopic crystals that are a compound containing mesostructured NPs and are involved in inactivating enveloping [52] and non-enveloping [53] viruses. Tungsten carbide nanoparticles also have extensive antiviral activity [54]. AgNPs also have various medical, environmental, and industrial applications as disinfectants [55]. These compounds have antiviral activity against several types of viruses, including RSV, HBV, and HIV [56]. These nanoparticles can also be used in air filters [55] and clothing fabrics [57]. Maghareh Abed et al. 5 8. Nano-based vaccines Many efforts are currently underway to develop the COVID-19 vaccine, including clinical trials. Nanotechnology approaches can help develop nano- based vaccines. The apparent similarity of SARS-CoV- 2 with other viruses (mainly SARS-CoV-2 and MERS- CoV) and the therapeutic progress and challenges of SARS-CoV-2 infection with other infectious diseases as well as oncological research are not significantly different [58], and it can help a lot in making a successful COVID-19 vaccine [59]. Vaccine production has significant similarities in the fight against SARS, MERS coronaviruses [16]. On the other hand, Conventional vaccines have problems such as the risk of reversal of viral virulence (live attenuated virus vaccines), weak immune response (inactivated viruses), and limited immunogenicity (subunit vaccines) [15]. Another advantage of vaccine nanocarriers is their size. Many biological systems, such as viruses, including the SARS-CoV-2 virus and some proteins, are nano-scale [16]. In this way, nanoparticles can be loaded with a wide range of antigenic components which is very important in the production of vaccines [60]. Nanoparticles can also target both humoral immune systems and cell-mediated immunity [61]. Modulation of antigen-presenting cells (APCs) using nanoparticles is of particular importance in vaccine fabrication [62]. Organic nanoparticles such as liposomes, lipid-based NPs, and polymeric NPs are significant in vaccine formulations [24]. Also, biopolymer-based NPs, like protein-based NPs, have low toxicity and biodegradability [63]. AuNPs, as another nanosystem for vaccine production, have been studied on more than 45 pathogens in various sizes, shapes, and functions [64]. 9. Conclusion The outbreak of the COVID-19 virus over the past year has led to the infection of a large population of the world and high mortality. As a result, rapid progress in discovering ways to diagnose, treat, and control the disease is a necessity. Early and rapid diagnosis of the disease, rapid and effective treatment measures, the use of appropriate and safe equipment are the most important strategies to control the disease. Currently, the diagnosing method of this disease is time- consuming and it is not applicable in public populations and far from urban health centers. On the other hand, many therapeutic approaches to this disease are based on symptomatic treatment and are performed using antiviral drugs previously used in other viral diseases. These drugs prevent the virus from being absorbed into the tissue and block the activity of proteases in infected cells. However, this strategy only reduces the number of viruses and the symptoms. According to reports, the most important barrier to the use of these drugs is their delivery to target cells and tissues in the respiratory tract, which reduces their effectiveness. Use methods based on nanotechnology is one of the best ways to overcome these barriers. Due to the aerodynamic size of the nanoparticles, they can be effective in predicting the treatment process. Also, the lack of an approved vaccine with high efficacy and low side effects is another problem and obstacle in controlling the disease. The unpredictable and unknown nature of the disease and the similarity of the specific properties of COVID-19 and the physicochemical properties of nanosystems have led to the discussion of solutions based on new technologies. This study attempts to review possible strategies for the prevention, diagnosis, and treatment of COVID-19 by focusing on current experiences and knowledge about nanotechnology and its successful measures in curing other viral diseases. 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