Recent Advancement in SARS-CoV-2 Diagnosis, Treatment, and Vaccine Formulation: a New Paradigm of Nanotechnology in Strategic Combating of COVID-19 Pandemic


Purpose of Review

The coronavirus disease-2019 (COVID-19) is a global pandemic which has not been seen in recent history, leaving behind deep socioeconomic damages and huge human losses with the disturbance in the healthcare sector. Despite the tremendous international effort and the launch of various clinical trials for the containment of this pandemic, no effective therapy has been proven yet.

Recent Findings

This review has highlighted the different traditional therapeutic techniques, along with the potential contribution of nanomedicine against the severe acute respiratory syndrome corovirus-2 (SARS-CoV-2). Repositioning of the drugs, such as remdesivir and chloroquine, is a rapid process for the reach of safe therapeutics, and the related clinical trials have determined effects against COVID-19. Various protein-based SARS-CoV-2 vaccine candidates have successfully entered clinical phases, determining positive results. The self-assembled and metallic nanovaccines mostly based on the antigenic properties of spike (S) protein are also approachable, feasible, and promising techniques for lowering the viral burden.


There are number of NP-based diagnostic systems have been reported for coronaviruses (CoVs) and specifically for SARS-CoV-2. However, extensive studies are still necessary and required for the nanoparticle (NP)-based therapy.


The outbreak of coronavirus disease-2019 (COVID-19) began in Wuhan, China. The corona virus global crisis is posing unprecedented difficulties to humans [1]. This new social landscape requires collective consideration, where our actions are interrelated, interdependent, to trans-boundaries and cultural diversity [2, 3]. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recognized as the causative agent of this revolution and grown by smooth tissues such as the muzzle, mouth, and nose [4, 5]. The SARS-CoV-2 is a single-stranded ribonucleic acid (ssRNA) virus having a short genome of 26–32 kb with a diameter of 65–125 nm, and earlier known to be a 2019-novel coronavirus (2019-nCoV) [6, 7]. The infection expanded quickly everywhere in China within a month, and according to the World Health Organization (WHO), it is recently expanded to over 212 countries, regions, and provinces worldwide [8, 9]. Based on clinical evidence, there are two major requirements to control the COVID-19 pandemic: first to overcome infection rates and second to reduce mortality [10]. Recently, no approved drugs or vaccines are prepared for the treatment or prevention of COVID-19 [11]. Still, the ongoing vaccines are in the second and third phases of clinical trials. As the accessible therapies, including nonspecific antivirals, antibiotics, to treat secondary bacterial diseases, sepsis, and corticosteroids to decrease inflammation fail to treat the severe illness with COVID-19 [12, 13]. This appears as inflammatory lesions with ground-glass ambiguity on computed tomography (CT) scans. The current accessible drugs have been able to moderately handle indications. Therefore, the appropriate and effective medical treatment for the current COVID-19 infection is an immediate demand for mankind [10]. Early detection of the infection is essential for defence among all states including symptomatic and asymptomatic populace [3, 11, 14]. Numerous forthcoming drugs that are thought to be unswervingly appropriate, as well as new therapeutic drugs are being produced, including viral entry inhibitors, replication inhibitors, protease inhibitors, heterocyclic antivirals, nanodrug delivery systems, and biological therapeutic drugs [15].

In the name of health as our primary necessity, the common interest should be addressed in the future, keeping in mind the “One Health” concept, relying on the belief that the well-being of humans is stringent with animals’ connections and environment [16]. To tackle such a complex challenge, the collaboration between diverse researchers with complementary expertise is needed. The current challenge should be taken as an incredible opportunity to remind us of our globalized world, as shown in other scientific contexts, a multi-interdisciplinary methodology involving transversal disciplines of knowledge between countries [17]. Promoting exchanges and increasing diversity in teams will all be necessary to obtain new and important scientific solutions [18]. From this point of view, nanotechnology is inherently an area in which scientists with incredibly diverse backgrounds have converted into valuable cooperations for multifaceted difficulties. Now, nanotechnology is required to lay new foundations towards combating the recent global public health threat and rethinking a more sustainable future based on science [19]. Nanoparticles (NPs) are small, but have a large surface-to-volume ratio, giving them unprecedented, unique features. Because of these characteristics, nanoparticles have been used in the fields of biotechnology, medicine, drug delivery, sensors, and DNA labelling and are treated as a bridge between bulk materials [20]. The nano-strategies have been widely applied to enhance antiviral drug delivery and efficiency, individually in combination with nucleoside analogues which have potential applications against drug-resistant human immunodeficiency virus disease also [15, 21]. There are several available nano delivery systems can be used with newly developed drug formulations to efficiently deliver drugs with rapid therapeutic indices for COVID-19. However, this work is in growth phase, and no nanotechnology is recently available for the treatment of COVID-19 so far. Even nanotechnology plays a pivotal role in the analysis of COVID-19 [22]. In this review, authors explain the possible role of nanotechnology in the diagnosis, investigation, vaccine formulation, and reasonable treatment of COVID-19.

Nanoparticle-Based Diagnosis of Coronavirus

The diagnosis of coronaviruses (CoVs) including SARS-CoV-2 is primarily based on computing tomography scans and nucleic acid testing that utilize reverse transcription polymerase chain reaction (RT-PCR) technique [23, 24]. The rapid analysis and recognition of infected patients are the most ideal approaches to contain scourges and typical-to-traditional diagnostic methods because of inaccessibility of facilities, instruments, reagents, low yield, and technical speciality. Because of urgent need for fast, sensitive, and economic testing of COVID-19, nanotechnology can play a crucial role in the diagnosis of SARS-CoV-2 using nanoparticle-based (NP-based) electromagnetic properties (Table 1) [35]. The test procedures require robotized extraction of nucleic acids from samples to prevent cross-contamination or false-negative outcomes. Magnetic nanoparticles (MNPs) are also employed in separation of nucleic acids. For instance, Zhao et al. built up a one-step nucleic acid isolation procedure utilizing amino-adjusted MNPs along with polycarboxyl groups (PC-coated NH2-MNPs) to tie viral RNA [25]. Under influence of magnetic fields, nucleic acid combines easily and delivered from MNPs by the expansion of buffer. Utilizing COVID-19 pseudoviruses, polycarboxyl MNPs (10 ± 3nm, − 39 ± 1 mV) indicated superior retention and paramagnetic properties at a magnetic capture of 30 s. Superparamagnetic NPs were set up to give a magnetite core secured with silica of 80 nm combined with probe that is corresponding to the target cDNA (complementary DNA) of SARS-CoVs. The functionalized superparamagnetic NPs had the option to strengthen and separate target cDNA from samples utilizing magnetic field [26]. This separated DNA was intensified with polymerase chain reaction (PCR) so that it could be effectively detected through sandwich hybridization assessment through silica-coated fluorescence NPs (40 ± 5 nm) bringing about fluorescence intensity, which is legitimately identified with the target cDNA concentration.

Table 1 Nanoparticle-based diagnosis for pathogenic coronaviruses

Gold nanoparticles (AuNPs) were investigated for developing nano assays for two reasons: (i) simplicity of electrostatic surface-design with different moieties, for example, antigens and antibodies; and (ii) SPR transition and change in colour [35, 36]. The AuNPs are most commonly utilized in colorimetric hybridization tests such as disulfide bond-based colorimetric assay designed by Kim et al. [27]. Utilizing thiolated single-stranded deoxyribonucleic acid (ssDNA) probes for targeting sites of Middle East respiratory syndrome coronavirus (MERS-CoV) genome for envelope protein (E) gene and open reading frame-1a (ORF-1a), framing a long self-assembled hybrid. This structure shields citrate ion-headed AuNPs from salt-actuated assembly. However, when target genes are absent, this protection is nonexistent, bringing about accumulation of AuNPs [27]. AuNP-based elementary hybridization assay was accounted for utilizing a DNA probe, which comprises thiolated-DNA comb immobilized on AuNP carbon terminal to hybridize biotinylated target DNA of SARS-CoV (Fig. 1) [28]. As a consequence of this, basic phosphatase streptavidin was formed through streptavidin-biotin association, catalyzing silver (Ag) ions and statement displacement of metallic Ag on anode surface. Metallic Ag can be estimated and it is in proportion to the concentration of alkaline phosphatase that target viral DNA [28].

Fig. 1

Nanoparticle-based assays for coronaviruses. a Colorimetric hybridization assays, b Electrochemical hybridization assays, c elctrochemical immunosensor assays

Chiral gold nanohybrids (CAuNPs) with quantum dots (QDs) have been recently utilized to build star-shaped chiroplasmonic AuNPs that can detect distinctive viral infections including CoVs [34]. In this technique, each of CAuNPs and QDs were conjugated to two distinctive target virus-targeted antibodies. When target virus is present, a nano-sandwich configuration was produced, bringing about predominant plasmonic resonant coupling with the beta particle of QD [34]. In addition, AuNPs can be intended to identify CoV-specific antibodies utilizing electromagnetic immunosensor assay consisting of a chip and a C-terminal that contains a variety of AuNPs to identify CoV-explicit antibodies (Fig. 1) [29]. Over the surface of AuNP-anodes, MERS-CoV protein was immobilized in the presence of antibodies with specific concentration; emulation took place between the free viruses in the prototype with immobilized MERS-CoV protein. A ferrocyanide probe was utilized for electrochromic estimation. This chip was utilized for multiplexed recognition simultaneously through numerous terminals on a similar chip, with every electrode connected to various viral antigens [29]. New indicative tests for SARS-CoV-2, for example, NP-based flow detection strips, were too augmented to accelerate detection and also eliminate the prerequisite to send samples at laboratories. Vertical stream (VF) detection was done to visually recognize nucleoprotein (N) gene of MERS-CoV in association with reverse transcription loop-interceded isothermal amplification method (RT-LAMP-VF) [30]. RNA of MERS-CoV was enhanced by RT-LAMP; the amplicons were labelled with fluorescein isothiocyanate (FITC) and biotin to bind streptavidin-AuNP conjugates. This FITC-labelled complex was procured by anti-FITC antitoxin immobilized on strip, delivering a hued line in 10 min [30]. The COVID-19 outbreak laid a global pressure on healthcare system, and there is urgency for the detection of positive coronavirus cases and carry out viral surveillance. Diagnostic survey may assume a significant part in COVID-19 identification, permitting quick implementation of preventive measures that confine the transmission by identifying and isolating positive cases. Opacities on CT scans of COVID-19-infected lungs are different from that of patients with healthy lungs: the anatomy of the lung is denser and more profused [37,38,39,40]. Presently, COVID-19 is analyzed by means of reverse transcriptase (RT)-PCR and visualized through CT; however, every procedure has some limitations. Techniques involving molecular reactions can analyze coronaviruses more precisely than CT scans, and they have the ability to locate and classify various microorganisms [22, 37]. Nanotechnology brings new technics for delivering economical and versatile detection techniques with effective prescriptions. Nano sensors are presently a reality and can identify low bacterial and viral concentrations. Subsequently, healthcare professionals are helping to identify symptoms. As indicated by the joint WHO taskforce and China, since December 2019 to mid-February 2020, 104 SARS-CoV-2 viral strains were separated and sequenced with Illumina and Oxford nanopore sequencing method [38]. Illumina sequencing is a grouping that involves synthetic procedure and solid-phase bridge intensifications, though nanopore sequencing includes movement of DNA through a protein pore and assessing changes in voltage to identify the sequence. Research and innovation are the only tools to fight against COVID-19. The equipment’s used in nanotechnology can be reframed for the analysis of disease [22, 39]. Distinctive nanotechnologies have advantages over molecular methods for diagnosing COVID-19, and the current strategies to combat the recent pandemic are addressed in detail.

Reverse Transcriptase Loop-Mediated Isothermal Amplification

Coronavirus is one of the deadliest respiratory infections which is quickly propagating overseas and has caused global concern. Presently, it is analyzed by SARS-CoV-2 nucleic acid through reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) combined with a nanoparticle-based biosensor (NBS) [41]. Other approaches are time-tedious and complex and require skilled specialists. Therefore, Yang et al. built up a RT-LAMP test to recognize triple genes for rapid diagnosis of SARS-CoV-2 [37]. In 2003, this technique was utilized to test for the SARS coronavirus and found to be simple and quick [42]. RT-LAMP, NBS-LAMP amplification method, and reverse transcription with nanoparticle-based biosensors enable diagnosis of COVID-19 in a single step. This technique requires 30 min for the amplification of nucleic acid at a consistent 60–65 °C utilizing various primers to distinguish the N, E, and ORF1ab gene sequence. Around ten sets of such primers have been configured per gene. The specificities of the COVID-19 RT-LAMP-NBS test was investigated by analysis of genomic sequence obtained from different microbes, including bacteria, fungi, and virus [22, 43].

Point-of-Care Testing

Purpose-of-care test procedure is followed when the patient samples are not sent to research facilities; this method does not require lab network to recognize patients who are infected. Lateral-flow antigen detection for SARS-CoV-2 is a consideration point being used for diagnosing COVID-19 [44]. Business lateral flow assays consist of a paper-like film strip covered with two lines: one consists of gold nanoparticle-antibody conjugate and another is used for antibody detection. Patient sample like blood, sputum, and urine are placed on the film; capillary movement attracts the protein through the line. At the point when the first line moves, antigens bind to the nanoparticle-antibody conjugate, after binding the complex streams across the film. The captured antibodies immobilize the complex after entering second side where the blue or red side is evident. Singular gold nanoparticles are red, while the coupled plasmon groups trigger the solvent enclosing the bundled gold nanoparticles to appear blue [23]. In research centres, numerous stages, for example, electrochemical sensors, paper-based frameworks, and surface-upgraded Raman spectrum-based systems are also established [22].

Optical Biosensor Nanotechnology

Optical biosensor nanotechnology is a new field of technology that enables the detection of the COVID-19 in only 30 min instantly from patients’ samples. This new innovation could undoubtedly decide if a patient is infected with the COVID-19 or flu infection [22]. This method will conceivably be utilized for procurement of patients and dealing with current pandemic situation. This novel biosensor device is also utilized for the analysis of different types of coronavirus diseases existing in animal body, for example, bats, cats, dogs, and sea animals, to identify and trace the possible evolutionary mechanism of these viruses for controlling such kinds of future outbreaks [22, 45].

Nanopore Target Sequencing

The nanopore target sequencing (NTS) technology detects SARS-CoV-2 with ten additional respiratory infections just in 6–10 h. This method is required contemporary for the diagnosis of COVID-19. Furthermore, the blueprint can also be extended to analyze different viruses and microorganisms. The NTS depends on intensification of eleven SARS-CoV-2 virulent virus and distinctive genomic sequence (e.g. ORF1ab) utilizing an essential band continued by sequencing of amplified section on a nanopore membrane [46]. This technique is based on a nanopore platform that sequences fragments of nucleic acid and simultaneously investigates the information near-real-time affirming SARS-CoV-2 diseases in few minutes by mapping the sequence read of SARS-CoV-2 genome for the analysis of identity and validity of outputs. The virulence locale (genome 21,563–29,674 bp; NC 045512.2) encoding spike (S, 1273 amino acid; AA), ORF3a (open reading frame 3a, 275 AA), envelope (E, 75 AA), membrane (M, 222 AA), ORF6 (66 AA), ORF7a (121 AA), ORF8 (121 AA), nucleocapsid (N, 419 AA), and ORF10 (38 AA) are helpful for the identification of SARS-CoV-2-virulent genomic sequence. The NTS is performed on one MinION sequencer chip (Oxford nanopore technique) to detect all test samples, the sequence info is determined through bioinformatics channelling at regular interval of timeframes. To expand plasmid concentration, all high-element reads were resolute by output reads on SARS-CoV-2 genome. As a norm for qPCR, NTS cannot decide that sample is positive for contagion via testing at one or two different domains; discoveries and information from all possible regions must be taken into consideration for further investigation [22, 47, 48].

Mechanism of Action of Antiviral Nanomaterials

Preclinical investigations have indicated virus nanoparticle reactions induce antiviral activity. Nanomaterials that work indirectly do not restrain virus alone; rather, they enhance the pharmacological action of antiviral medicines, and utilized for stability and better bioavailability [49,50,51]. Additionally, nanomaterials can likewise initiate an immune reaction for developing short-term immunity [52]. Interestingly, nanomaterials with direct activity act as dynamic compound, since they resist the viral infection alone, typically by changing the hereditary information of viral DNA. In 2005, Lara et al. demonstrated that receptors of HIV interact with AgNPs, restraining its infectivity [53]. They proposed that AgNPs bind to gp120 glycoproteins (GP) that prevent the virus to bind with cells, as noticed in the in vivo outcomes. Morris et al. has shown that AgNPs attach to surface GP of the virus preventing the association phenomenon by dropping its capability to attract cells [54]. Also, Cagno et al. proved that gold and iron oxide NP-coated ligands dislocate the configuration of numerous viruses [55], flouting the viral molecule that leads to denaturation of virus. Kim et al. exhibited that viral genes are suppressed by nanomaterials, the in vivo administration of anti-CCR5 siRNA/LFA-1 I-ts NPs silenced genes in leukocytes for approximately 10 days, inhibiting human immunodeficiency virus (HIV) disease [56]. Cojocaru et al. depicted the possible mode of action that permits nanomaterials to halt both DNA and RNA virus [57]. Among all the existing fundamental methods, inhibition of viral DNA/RNA is the major mechanism [58]. Nanomaterials show different characteristics of clinical intrigue, for example, upgraded chemical interactions, bio-compatibility, and controlled and targeted drug release, and were found safer when contrasted with the non-nanomaterials [59, 60].

Role of Nanotechnology in COVID-19 Treatment

COVID-19 outbreak requires impactful healthcare approaches for combating lethal lung infection. Until now, no particular medication is affirmed for the treatment of COVID-19 [61]. According to clinicians and therapeutic systems, a few immunomodulatory and antiviral drugs have been recommended and a number of drug verities are presently in phases of clinical trials. They include remdesivir, baricitinib, oseltamivir, EIDD-2801, favipiravir, darunavir/cobicistat, mRNA-1273, mycophenolate, tocilizumab, methylprednisolone, interferon, teicoplanin, ribavirin, hydroxychloroquine, and azithromycin [62]. On 28 March 2020, the Food and Drug Administration (FDA) permitted the use of hydroxychloroquine sulphate and chloroquine phosphate as an emergency prescription to fight against COVID-19 [63, 64]. As indicated by the most recent studies, regulations in Belgium, which additionally involved recommendations from Netherlands, Switzerland, France, and Italy, put forward the use of remdesivir, ritonavir/lopinavir, chloroquine or hydroxychloroquine, and tocilizumab for additional support; they also included use of O2 ventilator as a life support system and to save lungs from failure [65]. Favipiravir another antiviral medicine endorsed in China and Japan for curing flu is currently under audit for COVID-19 [66]. In addition to these prescriptions, Chinese drugs assume significant function to deal with coronavirus. The Chinese Academy of Sciences in collaboration with Shanghai Institute of Materia Medica recommended that SARS-CoV-2 can be treated utilizing an oral dose of Shuanghuanglian [67, 68]. The chemical composition of this fluid consists of baicalin, chlorogenic acid, and forsythin also demonstrated antiviral and bactericidal effects [69]. At present day 20 September 2020, none of the vaccine is approved for COVID-19; researches are ongoing in almost every country and are under pipeline, some are in phases I, II, and III. A vaccine developed by Oxford when tested on participant during clinical trial indicated serious neurological symptoms. Nanotechnology could have high chances for curing COVID-19 [69]. These can be utilized to decrease the severity and lethality of the disease (Table 2). Experimentations are under process and nano-based drugs will ideally be accessible soon.

Table 2 List of various types of nanoparticles used for the treatment of various viral infections

Nano systems with that work against SARS-CoV-2 have been summarized in Table 1. There are two main approaches to deactivate enveloped viruses. The first includes interaction between viral surface and nanomaterial for its inactivation. Nano system consists of hydrophobic layer that interacts with the lipid membrane present on viral surface encouraging denaturing. Examples possibly will be 1 (rGO) and 5 (CD); electrostatic interactions, 2 (SNP-DDAB), 4 (NCc), and 6 (GO); 3 (CQD modified with boronic acid); borono-lectin-sugar interaction, 7 (GO-Ag); combined dative bond and 8 (Ag-MHC); and dative bond interaction. Second approach deals with the nano system that entirely executes the virus. Both approaches are effective to act against SARS-CoV-2 [96]. Another approach using nanosystems, as previously mentioned, has an additional feature in them that can be used to kill viruses. In this regard, electromagnetic radiation has been employed to activate this additional characteristic either by reactive species or by photothermal heating. Therefore, viruses can be killed by oxidation or denaturation processes [96].

Miyako et al. [97] shaped carbon nanohorns (CNH) operationalized with a PEG derivative with PL (distearoylphosphatidylethanolamine) at one end and a T7 tag antibody (Ab) at the other end, NP sizes were of 50–150 nms. PEG has been incorporated to provide stability, PL to solubilize nanoparticles, and Ab to target T7 bacteriophage (T7 phage) as prototype virus. The overall impression (Fig. 2) signifies virus binding to the CNH, site-specific exclusion of the T7 phage exist via photothermal effect under NIR laser irradiation of 1064 nm. For control nanosystem, the Ab was not involved in NP system. Individually, both NS examined in presence and absence of Ab and found that they eliminated T7 phage upon NIR (near infrared) radiation (phage capsid proteins are denatured due to heat). When diluted suspensions of nanohorns were utilized, only marked NHs eliminated T7 phage [97].

Fig. 2

Antibody-antigen interaction between a targeted nanosystem and a virus with NIR absorption for photothermal heating to inactivate the virus

Baneerjee et al. [98] synthesized multi-walled carbon nanotubes (MWNT) with protoporphyrin (PPIX) as nanomaterial (NT-P) to decrease potential of influenza-A virus for infecting mammalian cells. Influenza strain X-31, A/Aichi/2/68 (H3N2), viruses tested and pulmonary mucoepidermoid carcinoma cell line NCI-H292 (ATCC# CRL-1848) were used. The NPs designed initially by acid-functionalized MWNT aminated PPIX and reacted under the influence of thionyl chloride. When NCI cells treated with NT-P in virus prominence, as a result of 90-min light irradiation, the infection was dropped to 1% while 78% infection was accomplished in dark system. This defines release of ROS by PPIX due to light and not MWNT. As anticipated, photobleaching is a key component of NT-P that may perhaps be reused five times. Meanwhile, the system generates ROS (that influences protein oxidation, ruptures RNA genomes, and crosslinks protein-RNA [99]); it could likely work against all types of influenza virus strain.

Nano Vaccine Models of Relevance in the Fight Against COVID-19

The nanotechnology can play a prime role to fight against COVID-19 utilizing nano vaccines, which contain nanoparticles and act as carriers of Ag that could activate defensive immune reactions. Antigen processing cells have ability of capturing microparticulate Ag complex to boost adaptive autoimmune responses that subsist with pathogen after entering inside an organism. Nanomaterials have inbuilt immunomodulatory properties that can impact therapeutic action of vaccine [100]. Hence, these can be a good choice to evade viral diseases. In this context, VLPs could be a leading approach for the development of safer nano vaccines due to highly immunized macromolecular complex, imitating antigenic effects of microorganism. The recombinant vaccines based on VLPs (vaccines against hepatitis B virus and human papillomavirus) are very much commercialized [101]. In addition to VLPs, other NPs have also been utilized in the field of vaccinology; some examples are liposome, gold NPs, chitosan, and PLGA [102]. Many researchers are targeting vaccines for SARS-CoV-1 and MERS-CoV and described in the works; these reports can be preliminary facts to develop SARS-CoV-2; among all, VLPs were utmost discovered strategy. Real-time expression of S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins of SARS-CoV serve to produce VLPs engaging baculovirus/insect cells; they depicted similar homologous characters with that of SARS-CoV virion when observed under an electron microscope [103, 104]. One report suggested that VLPs are formed within insect expressing M and E protein barely [105]. A set of four subcutaneous doses of VLP (mixed with Freund’s adjuvant) immunized to mice model leads to release of high Ab titers counter to SARS-CoV. VLPs provoked cellular resistance by enhancing IFN-γ and IL-4 production [106]. In another in vitro research, DCs triggered production of IL-6 and TNF-α after VLPs concocted with E and M proteins from SARS-CoV and S protein from a bat-isolated CoV. Furthermore, DCs pre-exposed to VLPs bring about an upsurge in the quantity of IFN-γ + IL-4 + CD4 + T cells [107]. For mucosal immunization (being documented as the most relevant), VLPs from SARS-CoV were examined in a mouse prototype exposed to intraperitoneal or intranasal vaccination. Both lead to SARS-CoV-specific IgG upregulation with increased levels in case of intraperitoneal route (i.p. route). Contrasting parenteral administration, intranasal delivery prompts IgA response that can be traced in the GIT and lungs. IgA level was higher for the i.p. immunization in the intestinal tract rather than intranasal route (i.n. route). However, secretions from the venereal region for mice vaccinated intranasally exhibited low response [108]. A number of studies indicate that VLPs are synthesized in the baculovirus/insect cell system by co-expression of M1 influenza protein and the S protein from SARS-CoV. The resultant chimeric VLPs remained analogous to the wild-type SARS-CoV when linking size and structure. The major troublesome task is to develop immunogenicity and defensive effectiveness, the chimeric VLPs totally saved mice after i.m. and i.n. immunization of SARS protein S [104, 109]. Rhesus macaques when immunized with VLPs and Al adjuvant exhibited release of T-helper 1 (Th1) cell-mediated immunity [104, 110]. Silkworm larvae and Bm5 cells were confirmed to synthesize vaccine contenders with the help of MERS-CoV inherent protein S, E, and M. Despite that E and M proteins are released and secreted to the culture supernatant, the S protein is absent as VLPs. Nanosized vesicle (100–200 nm through immune-TEM) displayed that S protein was produced from Bm5 cells stating operational proteins of the S protein via surface active agent processing and physical ejection [111]. Thus, the nanoformulation of COVID-19 vaccines might be more effectively helpful in the immunization against the current pandemic among students of higher education and understudies stakeholders in school education system too [112].


The data presented in the current review depicted that nanotechnology has allowed development of various biosensors, nanovaccines, and antiviral composites that are highly effective for close-related viruses; thus, it is a valuable guide for the agent’s development against SARS-CoV-2. Therefore, there is much more that nanotechnology has to offer in the fight against COVID-19 pandemic and the following months will be critical for the exploitation of unique characteristics of nanosized sensors, antiviral composites, and vaccines in the fight against this unprecendented global health crisis at multiple levels, especially for viral spread prevention and establishment of infection, but also in an accurate and timely diagnostic. For the proper containment of COVID-19 or any other emerging coronaviral pandemic, the detailed understanding of the virus virulence and the transmission are required which will enable a better understanding of virus transfer between species along with the identification of the differently encoded nanostructural enzymes and proteins and the related mechanism of action. Accordingly, new therapeutic targets can be recognized and targeted by the use of surface-functionalized NPs. Also, the study of the lifecycle of the virus and the host’s response will help us to produce effective nanovaccine. Based on these studies, the future aspect of a broad-spectrum ‘universal’ NP-based vaccine or therapeutic is expected to be ready for the current and future CoV pandemics. It can be predicted interestingly that microfluidics will have the contribution in CoV detection, taking the benefits of miniaturization, rapid detection, and portability. As the infection and spread of the viruses is way faster than the effective vaccines, vaccines and drug study should be complementary to what has already been achieved in the previous CoV-related research. The infection-to-mortality ratio because of current global health emergency has crossed the limits, making it different from other viral infections. The tools of nanotechnology can be modified and used for detecting, treating, and preventing the spread of COVID-19. Nanotechnology offers a unique set of tools which can help in the contribution and in the understanding of viral diseases and towards the critical development of therapeutic and diagnostic platforms.


  1. 1.

    Adhikari SP, Meng S, Yu-Ju W, Yu-Ping M, Rui-Xue Y, Qing-Zhi W, et al. Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: A scoping review. Infect Dis Poverty. 2020;9:29.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Upadhyay SK, Singh R, Babita KG, Singh G. The outbreak and challenges of novel coronavirus (COVID-19): The global pandemic emergency of early 2K20 and Indian scenario. Int J Biol Pharm Allied Sci. 2020;9:1173–99.

    CAS  Article  Google Scholar 

  3. 3.

    Yadav R, Parihar RD, Dhiman U, Dhamija P, Upadhyay SK, Imran M, et al. Docking of FDA approved drugs targeting NSP-16, N-protein and main protease of SARS-CoV-2 as dual inhibitors. Biointerface Res Appl Chem. 2020;11:9848–61.

    Article  Google Scholar 

  4. 4.

    Waris A, Khan AU, Ali M, Ali A, Baset A. COVID-19 outbreak: Current scenario of Pakistan. New Microbes New Infect. 2020;100681:100681.

    Article  Google Scholar 

  5. 5.

    Sood S, Aggarwal V, Aggarwal D, Upadhyay SK, Sak K, Tuli HS, et al. COVID-19 pandemic: From molecular biology, pathogenesis, detection and treatment to global societal impact. Curr Pharmacol Rep. 2020;6(5):212–27.

    CAS  Article  Google Scholar 

  6. 6.

    Kaul D. An overview of coronaviruses including the SARS-2 coronavirus-Molecular biology, epidemiology and clinical implications. Curr Med Res Pract. 2020;10(2):54–64.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Upadhyay SK, Singh R, Singh M, Kumar V, Yadav M, Aggarwal D, et al. COVID-19 in republic of India: A report on situation and precautionary strategies to global pandemic. Bull Environ Pharmacol Life Sci. 2020;9:39–48.

    Google Scholar 

  8. 8.

    Curley M, Thomas N. Human security and public health in Southeast Asia: The SARS outbreak. Aust J Int Aff. 2004;58:17–32.

    Article  Google Scholar 

  9. 9.

    Kumar G, Singh G, Bhatnagar V, Gupta R, Upadhyay SK. Outcome of online teaching-learning over traditional education during covid-19 pandemic. Int J Adv Trends Comput Sci Eng. 2020;9(5):7704–11.

    Article  Google Scholar 

  10. 10.

    Kumar S, Rathi B. Coronavirus disease COVID-19: A new threat to public health. Curr Top Med Chem. 2020;20(8):599–600.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Dan S, Pant M, Upadhyay SK. The case fatality rate (CFR) in SARS-COV-2 patients with cardiovascular disease (CVD): A global health risk paradigm in COVID-19 pandemic. Curr Pharmacol Rep. 2020;6:315–24.

    CAS  Article  Google Scholar 

  12. 12.

    Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020;19(3):149–50.

    CAS  Article  Google Scholar 

  13. 13.

    Jha D, Sharma V, Sharma JK, Kumar S, Sharma V, Kamboj P, et al. Plausible state-specific plans and recommendations to avert COVID-19 community transmission. Bull Pure Appl Sci Zool. 2020;39A(2):447–54.

    Article  Google Scholar 

  14. 14.

    Hashmi HAS, Asif HM. Early detection and assessment of COVID-19. Front Med. 2020;7:311.

    Article  Google Scholar 

  15. 15.

    Agarwal HK, Chhikara BS, Doncel GF, Parang K. Synthesis and anti-HIV activities of unsymmetrical long chain dicarboxylate esters of dinucleoside reverse transcriptase inhibitors. Bioorg Med Chem Lett. 2017;27:1934–7.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Capua I, Cattoli G. One Health (r) evolution: Learning from the past to build a new future. Viruses. 2018;10:725.

    Article  PubMed Central  Google Scholar 

  17. 17.

    Sumaryada T, Pramudita CA. Molecular docking evaluation of some Indonesian’s popular herbals for a possible COVID-19 treatment. Biointerface Res Appl Chem. 2020;11:9827–35.

    Article  Google Scholar 

  18. 18.

    Why interdisciplinary research matters. Nature. 2015;525:305.

  19. 19.

    Weiss C, Carriere M, Fusco L, Capua I, Regla-Nava JA, Pasquali M, et al. Toward nanotechnology-enabled approaches against the COVID-19 Pandemic. ACS Nano. 2020;14(6):6383–406.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Gnanasangeetha D, Sarala TD. One pot synthesis of zinc oxide nanoparticles via chemical and green method. Res J Mater Sci. 2013;2320:6055.

    Google Scholar 

  21. 21.

    Chhikara BS. Corona virus SARS-CoV-2 disease COVID-19: Infection, prevention and clinical advances of the prospective chemical drug therapeutics. Chem Biol Lett. 2020;7:63–72.

    CAS  Google Scholar 

  22. 22.

    Waris A, Ali M, Khan AU, Ali A, Baset A. Role of nanotechnology in diagnosing and treating COVID-19 during the pandemic. Int J Clin Virol. 2020;4:065–70.

    Article  Google Scholar 

  23. 23.

    Udugama B, Kadhiresan P, Kozlowski HN, Malekjahani A, Osborne M, Li VYC, et al. Diagnosing COVID-19: The disease and tools for detection. ACS Nano. 2020;14(4):3822–35.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020;395(10223):470–3.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    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. Bio Rxiv. 2020.

  26. 26.

    Gong P, He X, Wang K, Tan W, Xie W, Wu P, et al. Combination of functionalized nanoparticles and polymerase chain reaction-based method for SARS-CoV gene detection. J Nanosci Nanotechnol. 2008;8(1):293–300.

    CAS  Article  Google Scholar 

  27. 27.

    Kim H, Park M, Hwang J, Kim JH, Chung DR, Lee KS, et al. Development of label-free colorimetric assay for MERS-CoV using gold nanoparticles. ACS Sens. 2019;4(5):1306–12.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Martinez-Paredes G, Gonzalez-Garcia MB, Costa-Garcia A. Genosensor for SARS virus detection based on gold nanostructured screen-printed carbon electrodes. Electroanalysis. 2009;21(3–5):379–85.

    CAS  Article  Google Scholar 

  29. 29.

    Layqah LA, Eissa S. An electrochemical immunosensor for the corona virus associated with the Middle East respiratory syndrome using an array of gold nanoparticle-modified carbon electrodes. Mikrochim Acta. 2019;186(4):224.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Huang P, Wang H, Cao Z, Jin H, Chi H, Zhao J, et al. A rapid and specific assay for the detection of MERS-CoV. Front Microbiol. 2018;9(1101):1–9.

    Article  Google Scholar 

  31. 31.

    Genie A. Rapid COVID-19 antibody detection tests: Principles and methods. Accessed Mar 2020.

  32. 32.

    Xiang J, Yan M, Li H, et al. Evaluation of enzyme-linked immunoassay and colloidal gold-immunochromatographic assay kit for detection of novel coronavirus (SARS-Cov-2) causing an outbreak of pneumonia (COVID-19). Med Rxiv. 2020.

  33. 33.

    Radwan SH, Azzazy HM. Gold nanoparticles for molecular diagnostics. Expert Rev Mol Diagn. 2009;9(5):511–24.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Ahmed SR, Nagy E, Neethirajan S. Self-assembled star-shaped chiroplasmonic gold nanoparticles for an ultrasensitive chiro-immunosensor for viruses. RSC Adv. 2017;7(65):40849–57.

    CAS  Article  Google Scholar 

  35. 35.

    Abd Ellah NH, Gad SF, Muhammad K, Batiha GE, Hetta HF. Nanomedicine as a promising approach for diagnosis, treatment and prophylaxis against COVID-19. Nanomedicine. 2020;15(21):2085–102.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Laromaine A, Koh L, Murugesan M, Ulijn RV, Stevens MM. Protease-triggered dispersion of nanoparticle assemblies. J Am Chem Soc. 2007;129(14):4156–7.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Yang W, Dang X. Rapid detection of SARS-CoV-2 using reverse transcription RT-LAMP method. Med Rxiv. 2020.

  38. 38.

    Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565–74.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Chan WCW. Nano research for COVID-19. ACS Nano. 2020;14:3719–20.

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Chotiwan N, Brewster CD, Magalhaes T, Weger-Lucarelli J, Duggal NK, et al. Rapid and specific detection of Asian-and African-lineage Zika viruses. Sci Transl Med. 2017;9:eaag0538.

    Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Law S, Leung AW, Xu C. Severe acute respiratory syndrome (SARS) and coronavirus disease-2019 (COVID-19): From causes to preventions in Hong Kong. Int J Infect Dis. 2020;94:156–63.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Yang W, Dang X, Wang Q, Xu M, Zhao Q, et al. Rapid detection of SARS-CoV-2 using reverse transcription RT-LAMP method. Med Rxiv. 2020.

  43. 43.

    Fleming AB, Raabe V. Current studies of convalescent plasma therapy for COVID-19 may underestimate risk of antibody-dependent enhancement. J Clin Virol. 2020;127:104388.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Xiang J, Yan M, Li H, Liu T, Lin C, et al. Evaluation of enzyme-linked immunoassay and colloidal gold-immunochromatographic assay kit for detection of novel coronavirus (SARS-Cov-2) causing an outbreak of pneumonia (COVID-19). Med Rxiv. 2020.

  45. 45.

    Zhu X, Wang X, Han L, Chen T, Wang L, et al. Reverse transcription loop-mediated isothermal amplification combined with nanoparticles based biosensor for diagnosis of COVID-19. Med Rxiv. 2020.

  46. 46.

    Wang M, Fu A, Hu B, Tong Y, Liu R, et al. Nanopore target sequencing for accurate and comprehensive detection of SARS-CoV-2 and other respiratory viruses. Med Rxiv. 2020.

  47. 47.

    Liu R, Fu A, Deng Z, Li Y, Liu T. Promising methods for detection of novel coronavirus SARS-CoV-2. View. 2020;1(1):e4.

    Article  PubMed Central  Google Scholar 

  48. 48.

    Yu L, Tong Y, Shen G, Fu A, Lai Y, et al. Immunodepletion with hypoxemia: A potential high risk subtype of coronavirus disease 2019. Med Rxiv. 2020.

  49. 49.

    Herzog C, Hartmann K, Künzi V, Kürsteiner O, Mischler R, Lazar H, et al. Eleven years of Inflexal V-a virosomal adjuvanted influenza vaccine. Vaccine. 2009;27(33):4381–7.

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Alconcel SNS, Baas AS, Maynard HD. FDA-approved poly(ethylene glycol)-protein conjugate drugs. Polym Chem. 2011;2:1442–8.

    CAS  Article  Google Scholar 

  51. 51.

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

    CAS  Article  PubMed Central  Google Scholar 

  52. 52.

    Seto WK, Yuen MF. New pharmacological approaches to a functional cure of hepatitis B. Clin Liver Dis (Hoboken). 2016;8:83–8.

    Article  Google Scholar 

  53. 53.

    Lara HH, Ayala-Nuñez NV, Ixtepan-Turrent L, Rodriguez-Padilla C. Mode of antiviral action of silver nanoparticles against HIV-1. J Nanobiotechnol. 2010;8:1–10.

    CAS  Article  Google Scholar 

  54. 54.

    Morris D, Ansar M, Speshock J, Ivanciuc T, Qu Y, Casola A, et al. Antiviral and immunomodulatory activity of silver nanoparticles in experimental RSV infection. Viruses. 2019;11(8):732.

    CAS  Article  PubMed Central  Google Scholar 

  55. 55.

    Cagno V, Andreozzi P, D’Alicarnasso M, Silva PJ, Mueller M, Galloux M, et al. Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism. Nat Mater. 2018;17:195–203.

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Kim SS, Peer D, Kumar P, Subramanya S, Wu H, Asthana D, et al. RNAi-mediated CCR5 silencing by LFA-1-targeted nanoparticles prevents HIV infection in BLT mice. Mol Ther. 2010;18:370–6.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Cojocaru FD, Botezat D, Gardikiotis I, Uritu CM, Dodi G, Trandafir L. Nanomaterials designed for antiviral drug delivery transport across biological barriers. Pharmaceutics. 2020;12:171.

    CAS  Article  PubMed Central  Google Scholar 

  58. 58.

    Vazquez-Munoz R, Lopez-Ribot JL. Nanotechnology as an alternative to reduce the spread of COVID-19. Challenges. 2020;11(2):15.

    Article  Google Scholar 

  59. 59.

    Pulit-Prociak J, Banach M. Silver nanoparticles-A material of the future? Open Chem. 2016;14:76–91.

    CAS  Article  Google Scholar 

  60. 60.

    Ali A, Ahmed S. A review on chitosan and its nanocomposites in drug delivery. Int J Biol Macromol. 2018;109:273–86.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Peeri NC, Shrestha N, Rahman MS, Zaki R, Tan Z, Bibi S, et al. The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? Int J Epidemiol. 2020;49(3):717–26.

    Article  Google Scholar 

  62. 62.

    Ziaie S, Koucheck M, Miri M, Salarian S, Shojaei S, et al. Review of therapeutic agents for the treatment of COVID-19. J Cell Mol Anesth. 2020;5(1):32–6.

    Article  Google Scholar 

  63. 63.

    Song Z, Hu Y, Zheng S, Yang L, Zhao R. Hospital pharmacists’ pharmaceutical care for hospitalized patients with COVID-19: Recommendations and guidance from clinical experience. Res Soc Adm Pharm. 2020;17:2027–31.

    Article  Google Scholar 

  64. 64.

    Tobaiqy M, Qashqary M, Al-Dahery S, et al. Therapeutic management of patients with COVID-19: A systematic review. Infect Prev Pract. 2020;2(3):100061.

    Article  Google Scholar 

  65. 65.

    Donders F, Lonnée-Hoffmann R, Tsiakalos A, Mendling W, Martinez de Oliveira J, et al. COVID I. ISIDOG recommendations concerning COVID-19 and pregnancy. Diagnostics. 2020;10(4):243.

    CAS  Article  PubMed Central  Google Scholar 

  66. 66.

    Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review. JAMA. 2020;323(18):1824–36.

    CAS  Article  PubMed  Google Scholar 

  67. 67.

    Wang L, Wang Y, Ye D, Liu Q. Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence. Int J Antimicrob Agents. 2020;55(6):105948.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Kaura KK, Allahbadiab G, Singh M. A comprehensive review on epidemiology, aetiopathogenesis, diagnosis and treatment of the novel coronavirus syndrome–COVID-19. Iberoamerican J Med. 2020:110–23.

  69. 69.

    Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58–60.

    CAS  Article  Google Scholar 

  70. 70.

    Huy TQ, Hien Thanh NT, Thuy NT, Chung PV, Hung PN, le AT, et al. Cytotoxicity and antiviral activity of electrochemical-synthesized silver nanoparticles against poliovirus. J Virol Methods. 2017;241:52–7.

    CAS  Article  PubMed  Google Scholar 

  71. 71.

    Dynamiker. Clinical value of IgG/IgM detection for COVID-19. Accessed 16 Mar 2020.

  72. 72.

    Li W, Balachandran YL, Hao Y, Hao X, Li R, Nan Z, et al. Amantadine surface-modified silver nanorods improves immunotherapy of HIV vaccine against HIV-infected cells. ACS Appl Mater Interfaces. 2018;10(34):28494–501.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Joshy KS, Snigdha S, Anne G, Nandakumar K, Laly AP, Sabu T, et al. Chem Phys Lipids. 2018;210:82–9.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Kumar P, Lakshmi YS, Kondapi AK. Triple drug combination of zidovudine, efavirenz and lamivudine loaded lactoferrin nanoparticles: An effective nano first-line regimen for HIV therapy. Pharm Res. 2017;34(2):257–68.

    CAS  Article  PubMed  Google Scholar 

  75. 75.

    Joshy KS, George A, Jose J, Kalarikkal N, Pothen LA, Thomas S. Novel dendritic structure of alginate hybrid nanoparticles for effective anti-viral drug delivery. Int J Biol Macromol. 2017;103:1265–75.

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Li Y, Lin Z, Xu T, Wang C, Zhao M, Xiao M, et al. Delivery of VP1 siRNA to inhibit the EV71 virus using functionalized silver nanoparticles through ROS-mediated signaling pathways. RSC Adv. 2017;7:1453–63.

    CAS  Article  Google Scholar 

  77. 77.

    Du T, Liang J, Dong N, Lu J, Fu Y, Fang L, et al. Glutathione-capped Ag2S nanoclusters inhibit coronavirus proliferation through blockage of viral RNA synthesis and budding. ACS Appl Mater Interfaces. 2018;10:4369–78.

    CAS  Article  PubMed  Google Scholar 

  78. 78.

    Asgary V, Shoari A, Afshar Moayad M, ShafieeArdestani M, Bigdeli R, Ghazizadeh L, et al. Evaluation of G2 citric acid-based dendrimer as an adjuvant in veterinary rabies vaccine. Viral Immunol. 2018;31:47–54.

    CAS  Article  PubMed  Google Scholar 

  79. 79.

    Lancelot A, Clavería-Gimeno R, Velázquez-Campoy A, Abian O, Serrano JL, Sierra T. Nanostructures based on ammonium-terminated amphiphilic Janus dendrimers as camptothecin carriers with antiviral activity. Eur Polym J. 2017;90:136–49.

    CAS  Article  Google Scholar 

  80. 80.

    Chahal JS, Fang T, Woodham AW, Khan OF, Ling J, Anderson DG, et al. An RNA nanoparticle vaccine against Zika virus elicits antibody and CD8+ T cell responses in a mouse model. Sci Rep. 2017;7:1–9.

    CAS  Article  Google Scholar 

  81. 81.

    Muñoz A, Illescas BM, Luczkowiak J, Lasala F, Ribeiro-Viana R, Rojo J, et al. Antiviral activity of self-assembled glycodendro[60]fullerene monoadducts. J Mater Chem. 2017;5:6566–71.

    CAS  Article  Google Scholar 

  82. 82.

    Lee J, Morita M, Takemura K, Park EY. A multi-functional gold/iron-oxide nanoparticle-CNT hybrid nanomaterial as virus DNA sensing platform. Biosens Bioelectron. 2018;102:425–31.

    CAS  Article  PubMed  Google Scholar 

  83. 83.

    Halder A, Das S, Ojha D, Chattopadhyay D, Mukherjee A. Highly monodispersed gold nanoparticles synthesis and inhibition of herpes simplex virus infections. Mater Sci Eng. 2018;89:413–21.

    CAS  Article  Google Scholar 

  84. 84.

    Tong T, Hu H, Zhou J, Deng S, Zhang X, Tang W, et al. Glycyrrhizic-acid-based carbon dots with high antiviral activity by multisite inhibition mechanisms. Small. 2020;16:1–12.

    CAS  Article  Google Scholar 

  85. 85.

    FDA. Cellex qSARS-CoV-2 IgG/IgM rapid test. 2020. Accessed Apr 2020.

  86. 86.

    EDI™. Novel coronavirus COVID-19 ELISA kits. Epitope Diagnistics Inc. 2020. Accessed Apr 2020.

  87. 87.

    SYBCL. SARS-CoV-2 solution. Shenzhen Yhlo Biotech Co. Ltd. 2020. Accessed Apr 2020.

  88. 88.

    FDA. COVID-19 IgM/IgG system. DPP®. 2020. Accessed Apr 2020.

  89. 89.

    USFDA. US food and drug administration VITROS immunodiagnostic product anti-SARS-CoV2 total reagent pack. Ortho-Clinical Diagnosis Inc. 2020. Accessed Apr 2020.

  90. 90.

    Sure Biotech. Coronavirus (COVID-19) rapid test. 2020. Accessed Apr 2020.

  91. 91.

    Ye S, Shao K, Li Z, Guo N, Zuo Y, Li Q, et al. Antiviral activity of graphene oxide: How sharp edged structure and charge matter. ACS Appl Mater Interfaces. 2015;7(38):21571–9.

    CAS  Article  PubMed  Google Scholar 

  92. 92.

    LoczechinA SK. BarrasA, et al. Functional carbon quantum dots as medical countermeasures to human coronavirus. ACS Appl Mater. 2019;11(46):42964–74.

    CAS  Article  Google Scholar 

  93. 93.

    Elechiguerra JL, Burt JL, Morones JR, Camacho-Bragado A, Gao X, Lara HH, et al. Interaction of silver nanoparticles with HIV-1. J Nanobiotechnol. 2005;3(1):6.

    Article  Google Scholar 

  94. 94.

    Galdiero S, Falanga A, Vitiello M, Cantisani M, Marra V, Galdiero M. Silver nanoparticles as potential antiviral agents. Molecules. 2011;16(10):8894–918.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  95. 95.

    Chen YN, Hsueh YH, Hsieh CT, Tzou DY, Chang PL. Antiviral activity of graphene-silver nanocomposites against non-enveloped and enveloped viruses. Int J Environ Res Public Health. 2016;13(4):430.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  96. 96.

    Palestino G, García-Silva I, González-Ortega O, Rosales-Mendoza S. Can nanotechnology help in the fight against COVID-19? Expert Rev Anti-Infect Ther. 2020;18:1–16.

    CAS  Article  Google Scholar 

  97. 97.

    Miyako E, Nagata H, Hirano K, Sakamoto K, Makita Y, Nakayama KI, et al. Photoinduced antiviral carbon nanohorns. Nanotechnology. 2008;19(7):6.

    CAS  Article  Google Scholar 

  98. 98.

    Banerjee I, Douaisi MP, Mondal D, Kane RS. Light-activated nanotube–porphyrin conjugates as effective antiviral agents. Nanotechnology. 2012;23(10):105101.

    CAS  Article  PubMed  Google Scholar 

  99. 99.

    Schneider JE, Tabatabaie T, Maidt L, Smith RH, Nguyen X, Pye Q, et al. Potential mechanisms of photodynamic inactivation of virus by methylene blue I. RNA–protein crosslinks and other oxidative lesions in Qβ Bacteriophage. Photochem Photobiol. 1998;67(3):350–7.

    CAS  Article  PubMed  Google Scholar 

  100. 100.

    Bhardwaj P, Bhatia E, Sharma S, Ahamad N, Banerjee R. Advancements in prophylactic and therapeutic nanovaccines. Acta Biomater. 2020;108:1–21.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  101. 101.

    Gilca V, Sauvageau C, Boulianne N, de Serres G, Couillard M, Krajden M, et al. Immunogenicity of quadrivalent HPV and combined hepatitis A and B vaccine when co-administered or administered one month apart to 9-10 year-old girls according to 0-6 month schedule. Hum Vaccine Immunother. 2014;10(8):2438–45.

    Article  Google Scholar 

  102. 102.

    Singh R, Upadhyay SK, Singh M, Sharma I, Sharma P, Kamboj P, et al. Chitin, chitinases and chitin derivatives in biopharmaceutical, agricultural and environmental perspective. Biointerface Res Appl Chem. 2021;11(3):9985–10005.

    CAS  Article  Google Scholar 

  103. 103.

    Mortola E, Roy P. Efficient assembly and release of SARS coronavirus-like particles by a heterologous expression system. FEBS Lett. 2004;576(1-2):174–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Wang C, Zheng X, Gai W, Zhao Y, Wang H, Wang H, et al. MERS-CoV virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques. Oncotarget. 2017;8(8):12686–94.

    Article  PubMed  Google Scholar 

  105. 105.

    Ho Y, Lin PH, Liu CY, Lee SP, Chao YC. Assembly of human severe acute respiratory syndrome coronavirus-like particles. Biochem Biophys Res Commun. 2004;318(4):833–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Lu X, Chen Y, Bai B, Hu H, Tao L, Yang J, et al. Immune responses against severe acute respiratory syndrome coronavirus induced by virus-like particles in mice. Immunology. 2007;122(4):496–502.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Bai B, Hu Q, Hu H, Zhou P, Shi Z, Meng J, et al. Virus-like particles of SARS-like coronavirus formed by membrane proteins from different origins demonstrate stimulating activity in human dendritic cells. PLoS One. 2008;3(7):e2685.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  108. 108.

    Lu B, Huang Y, Huang L, Li B, Zheng Z, Chen Z, et al. Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in mice. Immunology. 2010;130(2):254–61.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  109. 109.

    Liu YV, Massare MJ, Barnard DL, Kort T, Nathan M, Wang L, et al. Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV. Vaccine. 2011;29(38):6606–13.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  110. 110.

    Schijns V, Fernandez-Tejada A, Barjaktarovic Z, Bouzalas I, et al. Modulation of immune responses using adjuvants to facilitate therapeutic vaccination. Immunol Rev. 2020;296:169–90.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  111. 111.

    Kato T, Takami Y, Kumar Deo V, Park EY. Preparation of virus-like particle mimetic nanovesicles displaying the S protein of Middle East respiratory syndrome coronavirus using insect cells. J Biotechnol. 2019;306:177–84.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  112. 112.

    Garg S, Aggarwal D, Upadhyay SK, Kumar G, Singh G. Effect of COVID-19 on school education system: Challenges and opportunities to adopt online teaching and learning. Hum Soc Sci Rev. 2020;8(6):10–7.

    Article  Google Scholar 

Download references


Authors would like to express their gratitude to the facilities provided by Maharishi Markandeshwar (Deemed to be University) Mullana-Ambala (Haryana), India, for carrying out this work.

Author information



Corresponding author

Correspondence to Sushil Kumar Upadhyay.

Ethics declarations

Conflict of Interest


Human and Animal Rights and Informed Consent

The article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Clinical Pharmacology

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Upadhyay, S.K., Dan, S., Girdhar, M. et al. Recent Advancement in SARS-CoV-2 Diagnosis, Treatment, and Vaccine Formulation: a New Paradigm of Nanotechnology in Strategic Combating of COVID-19 Pandemic. Curr Pharmacol Rep 7, 1–14 (2021).

Download citation


  • COVID-19
  • SARS-CoV-2
  • Nanomedicine
  • Nanovaccines
  • Nano-based diagnosis