Exploiting Nanotechnology To Target Viruses

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-of-nanotechnology-and-nanomaterialsJournal of Nanotechnology and NanomaterialsReview ArticleExploiting Nanotechnology to Target VirusesSérgio Antunes Filho, Otávio Augusto Leitão dos Santos, Mayara Santana dos Santos, Bianca PizzornoBackx*Universidade Federal do Rio de Janeiro, Campus Duque de Caxias, Brazil*Correspondence should be addressed to Bianca Pizzorno Backx; biapizzorno@caxias.ufrj.brReceived date: April 02, 2020, Accepted date: April 13, 2020Copyright: 2020 Filho SA, et al. This is an open-access article distributed under the terms of the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and sourceare credited.AbstractSince the early years, different civilizations have been affected by infectious diseases caused by bacteria, fungi, parasites, and,mainly, by viruses. Viruses from the beginning impacted socio-economic development, as well as leveraging different public healthproblems. Treatments with traditional methods, such as drugs and vaccines, are used to contain the spread of infectious diseases.However, these treatments are not enough. Thus, it is necessary to develop new therapeutic strategies, and the nanotechnologyassociated with medical devices stands out with great potential for diagnosis, prevention, and treatment of various infectiousdiseases. This review will present an overview based on nanotechnological concepts and applications with the main focus on viralinfections.Keywords: Nanotechnology; Nanoparticles; Nanotechnological applications; Virus; Antiviral; COVID-19IntroductionInfectious diseases caused by microorganisms of themost varied natures and by viral entities cause millions ofdeaths every year [1]. Around the world, viral infectionshave impacted civilizations’ circumstances since theearliest times, including the current panorama of theSARS-CoV-2 pandemic known as coronavirus diseasein 2019 (COVID-19). In this sense, in the last century,it is possible to mention some pandemics with globalepidemiological repercussions. With a pandemic peak in1918, the so-called ‘Spanish flu’ caused by the InfluenzaA virus of the H1N1 subtype, infected more than 500million people and caused 50 to 100 million deathsworldwide [2]. According to the Centers for DiseaseControl and Prevention (CDC), the Asian flu pandemic,which began and peaked in the years 1957-1958, causedmore than 1.1 million deaths worldwide [3]. Anotherhighly relevant pandemic occurred in 1968, where theso-called ‘Hong Kong flu’ was caused by the InfluenzaA virus of the H3N2 subtype and caused more than 1million deaths across the globe [4]. It is estimated thatthe virus Influenza A H1N1pdm09, which caused the2009 pandemic, caused 151,700 to 575,400 deaths inthe first 12 months of circulation of the viral entity [5].J Nanotechnol Nanomaterials. 2020Volume 1, Issue 1Currently, the World Health Organization estimates thatthere are 290 to 650 thousand deaths per year caused byseasonal infections of Influenza virus subtypes [6]. Thepandemic caused by COVID-19, with a pandemic peakin the current year of 2020, confirms several questionsabout the real perspective of the mortality rate of thedisease, the possibilities of sequelae after the cure of theinfection, among other vital issues in the areas of healthand of society [7]. It is worth mentioning that several datademonstrate that the majority of infected people are notdocumented because they are asymptomatic or have mildsymptoms, which facilitates the spread of COVID-19 [8].Nanoscience appears with the proposal to findalternatives that reduce or prevent the spread of virions.The use of nanoparticles can inactivate the viral particleor decrease its resistance on abiotic surfaces and in theintracellular environment [9]. Besides, there is also thedevelopment of nanotechnologies capable of combatingviral diseases. The use of nanosystems that target drugs,quantum dots, among other biomedical technologies, canattack the infections by directing them to the target site.There is also the use of viral substrates as vehicles ormolecular additives. Starting their physical-chemical11

Filho SA, dos Santos OAL, dos Santos MS, Backx BP. Exploiting Nanotechnology to Target Viruses. J NanotechnolNanomaterials. 2020; 1(1): 11-15.and biological properties, the fight against tumors occurswith the activation of the immune system directed tothat region of hyperplasia [10,11]. Therefore, in thisarticle, we will address several possibilities for timelynanotechnological applications. It will be possible tohighlight the potential of nanosciences in combating theviral entity.Physico-Chemical Influence of OrganicMaterials on the Biosynthesis andStabilization of Nanoparticlesdrugs. Besides that, new drugs that are successful in vitromay not be efficient when administered to patients [22].The significant advantage of nanotechnology is that thesize of the nanoparticles. The permeation in targets thatare anatomically inaccessible with common drugs is adifferent ability [23]. The ability to change its surfacecharge, through supramolecular interactions, allowsfor permeation through the cell membrane. It can be apossible alteration of its surface charge, which integratesthe nanosystem efficiently [24,25]. Many antiviralactivities were established for nanosystems. (Figure 1).In recent years, the development of ecologically correctscientific techniques has gradually grown to find newmedicinal solutions that do not pose a risk to humanand animal health, as well as the environment [12]. Inthis way, nanoparticle biosynthesis adapts to sustainableroutes using organic materials as nanoparticles’ formersand stabilizers instead of harmful toxic components [13].The biosynthesis of nanoparticles begins with a reductionprocess between the ions, followed by the growth andnucleation stage of the nanoparticles to establish acolloidal matrix with active principles. About this, thenanosystem may have antimicrobial, antioxidant, antiinflammatory properties, among others [14,15].Besides, nanoparticle biosynthesis can be mediated bydifferent organic materials available in nature, whetherthey are of plant or animal origin [16]. As an example ofthis, we can mention plants that have different specializedstructures capable of secreting essential oils due tothe accumulation of secondary metabolites. Beyondas inputs of animal origin, for example, propolis hassubstances that compose the group of polyphenols, suchas phenolic and flavonoid compounds [17,18]. Therefore,these substances are directly related to the antioxidantpotential of the nanosystem, since it is a fundamentalcharacteristic for the determination of an efficientsystem that has a colloidal dispersion and stabilizationof nanoparticles [19]. Therefore, this nanosystem, as wellas others, has characteristics and properties that can beadjusted in detail for different functions and applicationsthat provide efficient antiviral mechanisms of action.Nanosystems and Antiviral MechanismsOne of the most intriguing characteristics associatedwith viruses refers to the fact that they do not have theirmetabolism and independent reproduction. Thus, theyare not considered as living beings, as they need hostcells to ensure survival. They need the cellular machineryof the host cell to replicate its genetic material, whetherDNA or RNA, and produce new viral particles, so theyare mandatory intracellular parasites [20,21]. Scientistsaround the world are looking for solutions using existingJ Nanotechnol Nanomaterials. 2020Volume 1, Issue 1Figure 1: Possible interactions of nanosystems withviral particles.Nanomaterials have also been investigated to optimizethe methods of drug administration already used. Thisnew approach would make it possible to reduce toxicity.Also, it prevents the degradation of drugs by metabolism.It is possible to increase absorption and greater targetingof drugs to target cells and tissues [26].Silver nanoparticles (AgNPs) have broad antiviralaction for herpes simplex viruses (HSV), humanimmunodeficiency viruses (HIV), Hepatitis B virus(HBV), among others [27]. AgNPs still have theadvantage of having efficient, eco-friendly synthesisroutes. The antiviral properties of nanoparticles caninvolve interaction with nucleic acids or thiol groupsof proteins [28]. Besides, other mechanisms have beenreported. The interaction and fusion of HIV-1 to host cellswere prevented by the binding of AgNPs (coated by PVP,BSA, and carbon) to the gp120 glycoproteins of the viralenvelope. These proteins are essential for the admissionof the virus into host cells, such as lymphocytes, bybinding to CD4 receptors. It was also seen that AgNPswere able to inhibit infection regardless of tropism and isnon-toxic concentrations to cells [29]. In another study,AgNPs coated with 30-50 nm PVP added to neutralizing12

Filho SA, dos Santos OAL, dos Santos MS, Backx BP. Exploiting Nanotechnology to Target Viruses. J NanotechnolNanomaterials. 2020; 1(1): 11-15.antibodies increased their ability to prevent infectionof cells by HIV-1. These interactions are dependent onthe shape and size of the nanostructures. AgNP activityagainst the hepatitis B virus (HBV) has also been reported.The binding of AgNPs inhibited the replication of thevirus to DNA. The synthesis of RNA and the formation ofvirions was prevented [30].The gold nanoparticles (AuNPs) synthesized by the greenroute are not yet so evident [31]. AuNPs functionalizedwith sialic acids had the potential to inhibit infectionby the Influenza A virus. The binding of the virus to thesurface of host cells and subsequent infection depends onthe recognition of the sialic acid present in these cells bythe hemagglutinin protein present on the viral surface. Itis believed that AuNPs functionalized with sialic acid wereable to block the interaction of hemagglutinin with sugar.Thus, the virus cannot enter the cell [32]. It was observedthat nanoparticles that are 10 nm bound more efficientlyto the surface of the HIV-1 viral envelope. They wouldbe associated with interaction with residues exposed inthe existing gp120 glycoproteins [33]. AuNPs coated withglucose conjugated to the drugs abacavir and lamivudinebe able to inhibit viral replication in cell assays [34].Also, AuNPs were coated with mercaptobenzoic acid andconjugated to SDC-1721, a derivative of the antagonistTAK-779 for the CCR5 receptor. This receptor is essentialfor the entry of HIV-1 into T lymphocytes. The SDC-1721and AuNps alone did not show inhibitory effects for virusinfection. However, when AuNPsare conjugated to SDC1721, the results showed similar effects to TAK-779. Thereis an efficient inhibition of the fusion and entry of HIV1 with T lymphocytes. With these results, it is seen thatsmall, therapeutically inactive organic molecules can beconverted into highly active drugs by conjugating them tometallic nanoparticles [35].In the study with the functionalized gold nanoparticles,only those with 14 nm were able to block the InfluenzaA virus infection. The 2 nm AuNPs did not showsignificant results. With the change in the shape of thegold nanostructures, there are studies associated withvaccines based on gold nanorods that were tested forthe respiratory syncytial virus (RSV) because there is theinduction of production of T lymphocytes, which are cellsof the immune system [36].Copper nanoparticles (CuNPs), as well as AgNPs, havealso shown broad activity against different organisms.Copper is cheaper and readily available than silver [37].The antiviral potential was evaluated by copper iodidenanoparticles (CuINPs) against the strain of InfluenzaA virus that caused the 2009 epidemic. CuINPs wereable to act on viral proteins such as hemagglutinin andJ Nanotechnol Nanomaterials. 2020Volume 1, Issue 1neuraminidase, leading to degradation and inactivationof the virus through the formation of reactive oxygenspecies (ROS) [37]. CuINPs have also been studiedagainst the feline Calicivirus (FCV). A non-envelopedvirus that is highly resistant to organic solvents andsurfactants, unlike enveloped ones. This virus wasconsidered as a substitute for human norovirus that isassociated with gastroenteritis [38]. The virus infectioncapacity was significantly reduced during the exposure ofCrandell-Rees feline kidney cells (CRFK) to 1000 μg.ml-1CuINPs for 60 min, reaching a reduction of 7 orders ofmagnitude under these conditions. This effect was alsohypothesized to be the result of the production of ROSand the sequential oxidation of capsid proteins [38].It is urgent to establish options for human coronavirus(HCoV). However, anti-virus therapy is challenging, ascoronaviruses mutate rapidly and have wide diversity. Thefirst generation of nanostructures that demonstrated theinactivation of the virus was derived from hydrothermalcarbonization of ethylenediamine/citric acid as carbonprecursors and post-modified with boronic acid ligands,called carbon quantum dots (CQDs). These nanostructuresshowed concentration-dependent virus inactivation.CQDs derived from 4-aminophenyl boronic acid arethe second generation of anti-HCoV nanomaterials.These nanostructures showed concentration-dependentvirus inactivation. CQDs derived from 4-aminophenylboronic acid are the second generation of antiHCoV nanomaterials. With an average size of 10 nm,have excellent dispersion in water. Have no toxicityassociated with animals, so promise to be an advanceassociated with nanomedicine [39]. Characteristics ofthe nanostructures related to shape, size, and chemicalsurface are essential for the access of these nanometricstructures to the attack target. The interactions withthe biological environment and properties of the cellmembrane, as a particular charge and affinity with water(hydrophilicity or hydrophobicity), can influence thecell absorption ways. This feature would allow drugs toefficiently access virus reservoirs. In the case of SiO2NPsnanoparticles, these nanostructures interact stronglywith viral particles due to hydrophobic or hydrophilicproperties. It can establish stronger interactions with aspecific virus envelope with similar surface properties.The antiviral activity of SiO2NPs particles suggests amechanism of antiviral action for anti-HIV therapy, basedon surface interactions between silica, cells, and viruses[40]. For H1N1 influenza virus types A and B, one of themost widely used antiviral drugs are oseltamivir (OTV).When there is an association of this drug with seleniumnanoparticles (SeNPs), the delivery of the drug, throughthe use of an association between OTV and SeNPs, is muchmore efficient to prevent H1N1 infection with low toxicity[41]. Bacterial viruses are called when the virus infects13

Filho SA, dos Santos OAL, dos Santos MS, Backx BP. Exploiting Nanotechnology to Target Viruses. J NanotechnolNanomaterials. 2020; 1(1): 11-15.the bacteria. The bacteriophage virus MS2 is an examplethat infects the bacteria Escherichia coli. Studies indicatethat titanium dioxide (TiO2) nanoparticles modified withsilver commenced inactivation to the MS2 virus about fivetimes higher when compared to titanium nanoparticleswithout doping. The evolution of virus inactivation wasfavored by the increase in silver doping, due to the actionalready mentioned above [42].ConclusionThe potential of nanomaterials has attracted severalinterests in approaches to viral infections since they canbe designed to act directly against viruses or increase thecapacity of drugs already used today. In this sense, furtherstudies will be necessary to deepen the knowledge aboutantiviral mechanisms. Therefore, various tests must takeplace in vitro and in vivo to apply nanosystems associatedwith reducing the spread of viruses, in addition toexpanding the advantages of using nanostructures in newtherapies or vaccines capable of stopping the rapid actionof these viral particles. From this, it is worth emphasizingthe importance of knowledge about the immune system,since it interacts and responds to these nanomaterialsto optimize better constructions and avoid toxic effectson the body. Therefore, through all the data cited in thetext above, it can be observed that nanotechnology hasbeen a promising science in the search for alternatives toconventional treatments against diseases caused by viralparticles.References1. WHO. The top 10 causes of death. World ed2020.2. Liu WJ, Bi Y, Wang D, Gao GF. On the centenary ofthe Spanish flu: being prepared for the next pandemic.Virologica Sinica. 2018 Dec 14;33(6):463-6.3. Resistance IA. Questions and Answers. Centers forDisease Control and Prevention (CDC) & National Centerfor Immunization and Respiratory Diseases (NCIRD),July 23, 2012.4. CDC. Centers for Disease Control and Prevention,National Center for Immunization and RespiratoryDiseases (NCIRD) 1968 Pandemic (H3N2 virus). ndemic.html. Accessed 2020.5. Dawood FS, Iuliano AD, Reed C, Meltzer MI, ShayDK, Cheng PY, Bandaranayake D, Breiman RF, BrooksWA, Buchy P, Feikin DR. Estimated global mortalityassociated with the first 12 months of 2009 pandemicJ Nanotechnol Nanomaterials. 2020Volume 1, Issue 1influenza A H1N1 virus circulation: a modelling study.The Lancet Infectious Diseases. 2012 Sep 1;12(9):687-95.6. WHO. Burden of disease. World Health lancemonitoring/bod/en/ Accessed 2020.7. Lipsitch M, Swerdlow DL, Finelli L. Defining theepidemiology of Covid-19—studies needed. New EnglandJournal of Medicine. 2020 Feb 19.8. Li R, Pei S, Chen B, Song Y, Zhang T, Yang W, ShamanJ. Substantial undocumented infection facilitates therapid dissemination of novel coronavirus (SARS-CoV2).Science. 2020 Mar 16.9. Kerry RG, Malik S, Redda YT, Sahoo S, Patra JK,Majhi S. Nano-based approach to combat emerging viral(NIPAH virus) infection. Nanomedicine: Nanotechnology,Biology and Medicine. 2019 Jun 1; 18:196-220.10. Manchester M, Steinmetz NF. Viruses andnanotechnology. Berlin: Springer-Verlag; 2009.11. Gerrard JA, Domigan LJ. Protein Nanotechnology.Methods in Molecular Biology. 2020;2073.12. Backx BP, Pedrosa BR, Delazare T, Damasceno F,Santos O. Green synthesis of silver nanoparticles: a studyof the dispersive efficiency and antimicrobial potentialof the extracts of Plinia cauliflora for application insmart textiles materials for healthcare. Journal ofNanomaterials & Molecular Nanotechnology. 2018;7(1).13. Prasad R. Synthesis of silver nanoparticles inphotosynthetic plants. Journal of Nanoparticles.2014;2014.14. Oliveira KA, De M. Antimicrobial activity andquantification of total flavonoids and phenols in differentextracts of propolis. Seminar: Biological and HealthSciences. 2013;211–222.15. Thakkar KN, Mhatre SS, Parikh RY. Biologicalsynthesis of metallic nanoparticles. Nanomedicine:Nanotechnology, Biology and Medicine. 2010 Apr1;6(2):257-62.16. Santos DSM, Santos DLAO, Filho AS, SantanaSDCJ, de Souza MF, Backx BP. Can green synthesis ofnanoparticles be efficient all year long? NanomaterialChemistry and Technology. 2019;1(1):32-36.17. Backx BP. Green Dispersive Systems and theFormation of Micro-and Nanostructured Multiphase inLeaves Extract from Psidium guajava L. SciFed NanotechResearch Letters. 2018 Aug 14;2(2).18. dos Santos MS, Backx BP. A própolis e abionanotecnologia. A Interface do Conhecimento sobreAbelhas. 1th ed. Atena Editora. 2019.14

Filho SA, dos Santos OAL, dos Santos MS, Backx BP. Exploiting Nanotechnology to Target Viruses. J NanotechnolNanomaterials. 2020; 1(1): 11-15.19. López-Esparza R, Altamirano B, Pérez E, GamaGoicochea A. Importance of molecular interactions incolloidal dispersions. Advances in Condensed MatterPhysics. 2015;2015.20. Singh L, Kruger HG, Maguire GE, GovenderT, Parboosing R. The role of nanotechnology in thetreatment of viral infections. The

Filho SA, dos Santos OAL, dos Santos MS, Backx BP. Exploiting Nanotechnology to Target Viruses. J Nanotechnol Nanomaterials. 2020; 1(1): 11-15. J Nanotechnol Nanomaterials. 2020 Volume 1, Issue 1 13 antibodies increased their ability to prevent infection of cells by HIV-1. These interactions are dependent on the shape and size of the .

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