key: cord-0921930-s9bj29se
authors: Panda, Subhasree; Deshmukh, Kalim; Mustansar Hussain, Chaudhery; Khadheer Pasha, S. K.
title: 2D MXenes for Combatting COVID-19 Pandemic: A Perspective on Latest Developments and Innovations
date: 2022-04-30
journal: FlatChem
DOI: 10.1016/j.flatc.2022.100377
sha: fff70562d75f7748453144acd3d632510545141c
doc_id: 921930
cord_uid: s9bj29se

The COVID-19 pandemic has adversely affected the world, causing enormous loss of lives. A greater impact on the economy was also observed worldwide. During the pandemic, the antimicrobial aprons, face masks, sterilizers, sensor processed touch-free sanitizers, and highly effective diagnostic devices having greater sensitivity and selectivity helped to foster the healthcare facilities. Furthermore, the research and development sectors are tackling this emergency with the rapid invention of vaccines and medicines. In this regard, two-dimensional (2D) nanomaterials are greatly explored to combat the extreme severity of the pandemic. Among the nanomaterials, the 2D MXene is a prospective element due to its unique properties like greater surface functionalization, enhanced conductivity, superior hydrophilicity, and excellent photocatalytic and/or photothermal properties. These unique properties of MXene can be utilized to fabricate face masks, PPE kits, face shields, and biomedical instruments like efficient biosensors having greater antiviral activities. MXenes can also cure comorbidities in COVID-19 patients and have high drug loading as well as controlled drug release capacity. Moreover, the remarkable biocompatibility of MXene adds a feather in its cap for diverse biomedical applications. This review briefly explains the different synthesis processes of 2D MXenes, their biocompatibility, cytotoxicity and antiviral features. In addition, this review also discusses the viral cycle of SARS-CoV-2 and its inactivation mechanism using MXene. Finally, various applications of MXene for combatting the COVID-19 pandemic and their future perspectives are discussed.

havoc among people, creating greater health impacts and a higher level of mortalities. Not only the health illness but also the hazardous wastes generated during the pandemic has resulted in environmental pollution and greater spreading of the virus [5] . To combat this misery, researchers all over the world set out to discover advanced technologies for medication and vaccine delivery as well as to mitigate the spread of the virus.

The superior physicochemical properties of nanomaterials can be greatly explored to tackle this emergency. The extraordinary quantum mechanical properties of the nanomaterials can be utilized to build sophisticated biomedical instrumentations like photosterilizers, touchfree sanitizers, contact tracing tools, etc. [6] . The production rate and durability of biomedical delivery and prevention of cytokine release syndrome (CRS) [7] . The nanomaterials can also be used as potent biosensors for the detection of SARS-CoV-2 viruses and their related biomarkers ( Fig. 1) [7] . Fig. 1 . Prospective application of nanomaterials to combat the COVID-19 pandemic. Adapted from Ref. [7] , Copyright 2020, American Chemical Society.

Since the emergence of the pandemic, the development in finding a suitable vaccine has been progressing with a greater effort. The COVID-19 vaccines mainly rely on the administration of antigens based on the mRNA, DNA, recombinant proteins, viral vectors, and attenuated or inactivated viruses, focusing mostly on the inactivation of viral S proteins [8] .

However, the delivery of these therapeutics is hindered due to their vulnerability to enzymatic degradation and impermeability to cell membranes [9] . The polymeric, inorganic, or lipidbased nanoparticles can be used as encapsulation to avoid these issues and to provide effective non-invasive (nasal, oral, transdermal, pulmonary, etc.) methods for drug and vaccine delivery [9] . For improving the efficacy of vaccines and considering the mutation of the viruses, the nanomaterials can be functionalized with different types of molecules targeting specific pathogens [7] . Nanomaterials with specific and non-specific mechanisms of antiviral action can be administered to inhibit viral activity [10] . The nanomaterials having a specific mechanism of action target particular surface receptors or ligands of the virus, whereas the nanomaterials having a non-specific mechanism of action inhibit any part of the virion [10] .

The nanomaterials can modify the function of accessory proteins (ORF7a), spike glycoproteins (S), envelope (E), and membrane (M) proteins, etc. of the virus [10] . In cases the nanomaterials release various ions and therapeutics, that pass through the envelope to disrupt virus protein machinery by dysfunctioning the proteases like NSP3 (papain-like protease), NSP5 (main protease), NSP7, NSP8, NSP9 (RNA replicase), NSP10, NSP13 (helicase), etc. (Fig. 2a) [10] .

The nanomaterials also release the inhibitors of ACE2 and TMPRSS2 to inhibit the entry complex formation. If the virus breaks the barrier and enters the host cell, the nanomaterials provide the second line of defense by the disruption of virion endosomal acidification, intracellular vesicle formation for RNA transcription, blocking of crown shape molecular pores, packaging, and exocytosis of new virions, etc. (Fig. 2b) [10] . help for environmental remediation by the less exposure to disposable plastics made out of face masks and PPE kits, etc [12] . The enhanced photocatalytic and photothermal activities of MXenes can help to inactivate the virus [13, 14] , as well as the superior sensing activities, can help to build efficient biosensors that can detect the COVID-19 virus and other biomarkers in the case of patients having comorbidities [15] . The greater drug loading and point-specific drug release capacity of MXene can be utilized for delivering the drug in remote parts of the internal organs of COVID-19 patients [16] . Along with these, the greater biocompatibility and lesser cytotoxicity of MXene reduce the risk of poisoning as seen in the case of other advanced materials [17] .

Many advanced nanomaterials have been explored to date for the detection and inactivation of the SARS-CoV-2 virus, but they also have lots of limitations. Seo et al. [18] fabricated a graphene-based field-effect transistor (FET) biosensor by coating a specific antibody of SARS-CoV-2 spike protein. The COVID-19 FET sensor successfully detected the antigen protein as well as measured the viral load in culture medium and clinical samples. But, the device lacks resilience and requires pre-processing of the virus sample, due to the comparatively low signalto-noise ratio of the graphene sensing material. The MXene-graphene FET sensor fabricated by Li et al. [19] eliminated the loopholes of graphene-based FET sensor for the detection of the SARS-CoV-2 virus. The authors used a virus-sensing transduction material (VSTM) consisting of both MXene and graphene. They found that the enhanced performance is due to the hydrophilic surface functionalization and accordion-like structure of MXene that provides greater active sites for virus adsorption. The zero band gap of graphene also restricts its application as a biosensor for the fast and accurate detection of viruses, whereas the metallic nature of MXene provides a greater bandgap for sensing [20] . The transition metal dichalcogenides have a greater band gap, but the high electrical noise limits their sensing application [21] . MXene-based biosensors provide extremely low noise and ultrahigh signalro noise ratio, which is beneficial for rapid sensing activity [22] . MXenes have reported a greater adsorption capacity than graphene and a faster rate of removal than carbon nanotubes [23] . This property can be beneficial for faster adsorption and removal of virus, cytokines, and other biomarkers from the body of COVID-19 patients. Although MXenes have made tremendous progress in biomedical instrumentations and antimicrobial applications, their properties are less explored in the field of antiviral applications. Hence this review deeply studies the MXene antiviral properties as well as the perspectives of using MXene as a sword to win the battle against the COVID-19 pandemic.

MXenes are the large family of 2D transition metal carbides, nitrides, or carbonitrides, discovered in 2011 by Gogosti et al. [24] . They have a chemical formula of M n+1 X n T x (n=1 to 4), where M is an early transition metal (Ti, V, Cr, Nb, Mo, etc.), X is carbon and/or nitrogen, and T x indicates the surface termination groups like -F, -OH, -O, etc [15, 25] . Ti 3 C 2 T x , Ti 2 CT x , Ti 2 NT x , Ti 3 CNT x , V 2 CT x , Nb 2 CT x , Cr 2 TiC 2 T x , Ti 3 SiC 2 T x , Mo 4 VC 4 T x , etc. are some of the examples of synthesized MXenes from which the Ti 3 C 2 T x is the most explored one [26] . Till now more than 30 MXenes have been synthesized and more than 100 MXene stoichiometries have been predicted by simulations, making them one of the largest families of 2D materials [17] . The double transition metal MXenes are comprised of two transition metal atoms as compared to mono transition metal MXenes [27] . The double transition metal MXenes are of two types, i.e. solid solutions having a random distribution of transition metals in the M sites of the 2D structure ((Ti, Nb) 2 CT x , (Ti, V) 2 CT x , etc.) and ordered forms having in-plane (Mo 4/3 Y 2/3 CT x , Mo 4/3 Sc 2/3 CT x )/out-of-plane (Mo 2 TiC 2 T x , Mo 2 Ti 2 C 3 T x , Cr 2 TiC 2 T x , etc.) ordered structures (Fig. 3) [28] . MXenes derived their name from graphene due to their similar properties [29] . They have hexagonal layered structures similar to their parent MAX phases, in which the X layers are interleaved between the M layers with functional groups attached to the surface structure [30, 31] . The scanning electron microscopy (SEM) images confirm the lamellar structure of the MXenes [32] . The bonding between the M and A elements is purely metallic whereas the M-X bond combines the characteristics of covalent, ionic, and metallic bonds, but the M-A bonds are quite unstable as compared to the M-X bonds [29] . They have excellent physicochemical properties, which lead to their wide range of applications in energy storage devices, gas sensing, catalysis, electromagnetic interference shielding, and biomedical fields [13, 31, 33, 34] . Fig. 4 gives a representation of MXene applications in various sectors [31] . 

MXenes can be synthesized by both top-down and bottom-up methods [28] . In the topdown methods, the A layers are etched out from the 3D MAX or non-MAX phase precursors resulting in the 2D layered MXenes. The strong metallic bond between the M and A layers of the MAX phase resists its exfoliation by mechanical shearing methods [29] . The hightemperature treatment can exfoliate the A layers but the synthesized MXenes lose their layered structure due to recrystallization of the material [29] . Therefore the exfoliation of A layers can be achieved by using chemical etching methods like hydrofluoric acid (HF) etching, alkali etching, acid/fluoride salt etching, molten salt etching, and electrochemical etching, etc. followed by sonication or intercalation with organic bases or cations [35] . Intercalants like dimethyl sulfoxide (DMSO) [36] , urea [37] , isopropylamine [38] , hydrazine monohydrate [39] , tetrabutylammonium hydroxide (TBAOH) [40] , tetramethylammonium hydroxide (TMAOH) [41] , aryl diazonium salts [42] , etc. are commonly used for increasing the interlayer distance, thereby resulting in the efficient exfoliation of MXenes. Instead of these the cations like Al 3+ , Mg 2+ , Li + , Na + , K + , NH 4 + , etc. are intercalated spontaneously or electrochemically to achieve the exfoliated MXenes [43] . Fig. 5 illustrates etching, intercalation and delamination processes of MXenes [31] . Naguib et al. [44] synthesized the first MXene Ti 3 C 2 by etching the A layers of the Ti 3 AlC 2 MAX phase in 50% HF acid at RT for a duration of 2hr. This mechanism can be illustrated as follows, M n+1 AX n + 3HF  M n+1 X n (s) + AF 3 + 1.5H 2 (g)

(1) M n+1 X n (s) + 2HF  M n+1 X n F 2 + H 2 (g)

Although MXenes were tremendously etched out using HF, the hazardous and toxic nature of the acid discard it as an efficient etchant for MXene synthesis [45] . Hence more effective green synthesis methods were followed by the HF etching. Ghidiu films using NH 4 HF 2 as an etchant [52] . These etching processes result in the negative surface functional groups terminations on the MXene surface like -F, -OH, -O, etc., which is responsible for the formation of their stable colloidal solutions [53] . The structure and properties of the synthesized MXenes largely vary depending upon the atmospheric moisture and temperature, exposure to UV radiations, delaminating agents, etching time, etching solution, etc. [50] . For example, the increase in temperature helps in accelerating the exfoliation of MXenes but it leads to the enhancement of oxidation too [50] . Similarly, higher atomic number and larger bond energy MAX phases require high concentration etchants and greater etching time [29] . Conversely, as compared to the top-down methods, in the bottom-up methods, MXenes are synthesized by the combination of their corresponding atoms/molecules.

Xu et al. [54] first used this strategy to synthesize the MXene Mo 2 C by the chemical vapor deposition (CVD) method. Followed by this, other bottom-up methods like template method [55] , plasma-enhanced pulsed laser deposition method (PEPLD) [56] , etc. were discovered for the synthesis of MXenes. Fig. 6 describes the evolution of MXene synthesis methods over the past decade [57] . 

To study the antiviral properties of MXenes, it is essential to deeply understand the mechanism of virus infection. Coronaviruses are a group of encapsulated RNA viruses that have an approximate spherical structure with a dimension of 60-140 nm [58] . The club-like spike proteins emanating from the surface of the virion resemble the structure of a solar corona,

giving it the name coronavirus [59] . These viruses cause both acute and chronic illnesses in humans and animals. Among the six coronavirus species discovered so far, four of them cause common flu, whereas the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and

the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) are fatal [60, 61] . The SARS-CoV-2 is named so by considering the similarity of the virus with the previous SARS-CoV outbreak [62] . The genome sequence of the SARS-CoV-2 virus shows similarities with the previous strains of SARS-CoV and MERS-CoV but has a greater transmission rate. For example, the sequence analysis showed similarities of more than 80% with SARS-CoV and more than 50% with MERS-CoV [63] . The human cell entry receptors for both the SARS-CoV-2 and SARS-CoV variants are the same angiotensin-converting enzyme II (ACE2) protein [64] .

To develop drugs and vaccines for diagnosing the COVID-19 disease it is essential to understand the genomic sequence of the SARS-CoV-2 virus. The Global Initiative on Sharing

All Influenza Data (GISAID), a platform that provides open access genomic sequence data of the influenza viruses has reported 8 clades of the SARS-CoV-2 genomes, among which the mutated clades GR, S, and GH are found in most of the countries worldwide as compared to other clades having wild type genome [65] . Researchers have reported the missense mutation in the SARS-CoV-2 spike protein D614G as the predominant clade of viral infection in most countries, due to its greater binding affinity to ACE2 receptors, efficient cellular entry, and minimal antibody interactions [66] [67] [68] . This mutation has been found mostly in the GH and GR clades of the SARS-CoV-2 virus, making it more promising for the faster spreading of infection [17] .

The crystal structure study of the C-terminal domain of the SARS-CoV-2 spike S protein reveals the binding affinity of the virus to human ACE2 receptors [69] . The attachment of the spike S protein of the virus to the ACE2 receptor leads the Transmembrane serine protease 2 (TMPRSS2) to facilitate protease activity for cell entry [70] . As binding of the virus is a key factor for the initiation of infection, inhibition of this mechanism can lead to the reduction of viral infection to a greater extent. Treatments using recombinant ACE2, monoclonal antibodies, TMPRSS2 inhibitors, etc. have been widely recommended to impede viral binding [71] . Followed by the cell entry, the internalization of the virus occurs by endocytosis. The low pH of the endosome results in the uncoating of the viral genome and release into the cytoplasm for further viral RNA and protein synthesis, resulting in the assembly of viral infections ( Fig.   7 ) [7] . Several antiviral therapies have been administered to date for the regulation of viral RNA production, cytokine release, and blood coagulation, etc. [71] . [17] . The authors also studied the antiviral activities of Ti 3 C 2 T x , Ta 4 C 3 T x , Mo 2 Ti 2 C 3 T x , and Nb 4 C 3 T x MXenes by exposing them to the GR clade of the SARS-CoV-2 and found out Ti 3 C 2 T x to be the most potent antiviral among all of them [17] . Ti 3 C 2 T x exhibited 99% viral copy numbers reduction at a concentration of 0.32 µg/ml (1: 3,125 dilution), whereas Mo 2 Ti 2 C 3 T x reported a reduction of 95% viral copy numbers at a concentration of 100 µg/ml (Fig. 9B ) [17] . Nb 4 C 3 T x and Ta 4 C 3 T x did not show any significant antiviral activity either with GR and GH clades having D614G missense mutation or with other clades (Fig. 9A , C, E, F) [17] . The researchers also subjected the culture to TiO 2 nanoparticles to prove that, it's the Ti 3 C 2 T x MXene that exhibits antiviral activity and not the Ti particles ( Fig. 9D ) [17] . Ghasemi et al. [73] experimented with the interaction of Mo 2 C, Ti 2 C, and Mn 2 C MXene nanosheets with the spike proteins of the SARS-CoV-2 virus and found out that

MXenes not only adsorb the spike proteins effectively but also modify their secondary structure. This hinders their interaction with the angiotensin-converting enzyme 2 (ACE2) receptors of human cells, which are responsible for the COVID-19 infection. The authors also observed a greater potential of Mn 2 C MXene for inhibiting the infection as compared to other

MXenes [73] . Ghasemy et al. [73] studied the antiviral activities of MXenes by doing in-silico molecular dynamics simulations. They exposed the nanosheets of Mo 2 C, Ti 2 C, and Mn 2 C to the spike proteins of the SARS-CoV-2 and analyzed the interaction of MXene exposed spike proteins with ACE2 receptors by molecular docking analysis. They reported docking energy of -351.7

kJ/mol for the interaction of spike proteins and ACE2 receptors without any exposure to

MXene. The re-docking analysis of MXene treated spike proteins and ACE2 receptors exhibited lesser interaction energies of -312.7, -271, and -253 kJ/mol for Mo 2 C, Ti 2 C, and

Mn 2 C MXenes, respectively. The authors attributed the lesser energy to the distorted structure of MXene treated spike proteins that hindered the interaction with ACE2 receptors. As reported in the literature, to diminish the stability of spike proteins, it is required to increase the turn, bend, and coil while decreasing the α-helices and -sheets of their secondary structure. Among the three MXenes, Mn 2 C reported the lowest docking energy revealing the highest portion of the turn, bend, and coil (Fig. 10a ). In accordance with the configurational analysis, the energy analysis of the interaction between MXenes and spike proteins reported the highest interaction energy for Mn 2 C MXene with an energy level of -290 kJ/mol [73] . The interaction energies for

Mn and Ti-based MXenes were favoured by van der Waals forces, whereas the interaction energies for Mo 2 C MXenes were dominated by electrostatic forces (Fig. 10b) . The entropy analysis of the interlinkage between spike protein and deformed spike protein with ACE2 receptors exhibited a lower entropy for the MXene treated spike proteins/ACE2 systems. This decrease in entropy revealed greater stability and suppression in the infection rate of the spike protein/ACE2 system. Mn 2 C MXene, having the greatest interaction energy reported the lowest entropy followed by Ti 2 C and Mo 2 C, respectively (Fig. 10c) . The decrease in the compactness of spike proteins led to a reduction in stability and weaker interaction with ACE2 receptors.

The compactness was measured by the difference in the initial and final radius of gyration. All

MXenes gave rise to a reduction in the radius of gyration, but Mn 2 C exhibited the most negative value of -0.3 (Fig. 10d ) [73] . This is in line with the impact of MXene on the secondary structures of spike proteins that reduce the number of active sites by structural molding. Fig.   10h and i show the conformation of the interaction between ACE2 and spike protein before and after the exposure to Mo 2 C MXene. Furthermore, the average number of hydrogen bonds (H-bonds) for the Mn 2 C exposed spike protein/ACE2 system was the lowest with an average number of 8, which confirms the lesser interactions of MXene treated spike proteins (Fig. 10e) .

In addition to this, the RDF analysis reported a lesser distribution of the MXene-mediated spike proteins in the vicinity of ACE2 receptors, revealing a lesser probability of infection (Fig. 10f) .

Moreover, the RDF analysis of the MXene/spike protein system reported the highest RDF value of 3.4 for the Mn 2 C/spike protein interaction, showing a greater affinity of Mn 2 C MXene to the spike proteins, compared to Ti 2 C and Mo 2 C MXenes (Fig. 10g) . The greater performance of Mn 2 C over Mo 2 C can be attributed to the smaller size of Mn atoms that offer a greater contact area with the spike proteins and contributes to a greater deformation. Despite the fact that Ti atoms are smaller than Mn atoms, the metallic nature of Mn 2 C promotes greater electron donation, resulting in the profound deformation of spike proteins [74] . Reproduced with permission from Ref. [73] , Copyright 2021, Taylor & Francis.

Studies have shown a relative inhibition of the COVID-19 virus activities with increasing temperature [75] . The elevated temperature disintegrates the genomic sequence of the virus, resulting in its inactivation [76] . With the increase in temperature, the disintegration becomes faster. The efficient photothermal properties of MXenes can help to kill the virus by facile optical to thermal conversion methods [14] . This property can be beneficial for the self- 

The biocompatibility and cytotoxicity of MXenes have been studied tremendously by many authors to foster their medical applications as nano agents for drug loading and vaccine delivery. Nasrallah et al. [82] studied the cytotoxicity of Ti 3 C 2 T x MXene using an in vivo [17] . The authors also exposed Ti 3 C 2 T x + LPS to the stimulated PBMCs population and found a notable reduction of the CD25 activation markers as compared to the LPS positive and negative control [17] . A similar reduction in the TNFα levels of the PBMCs supernatant was found with the treatment of Ti 3 C 2 T x + LPS as against the LPS positive control [17] . To study the impact of Ti 3 C 2 T x on human immune cells in detail, Unal and his coworkers identified 17 clusters of differentiation markers (CD) on the cell surface of PBMCs (10), T and B cells (7) respectively, using the single-cell mass cytometry technology (CyTOF) and applied viSNE computational approach to construct single-cell resolution plot [17] . With the help of this method, the researchers found 9 remarkable immune cells (CD 45+) populations i.e.,

CD4+Th. cells, CD8+Th. cells, B cells, C. monocytes, Int. monocytes, N. C. monocytes, natural killer cells (NKs), plasmacytoid and myeloid dendritic cells (pDCs and mDCs), respectively (Fig. 11E ) [17] . Using the method of Cisplatin staining, the ability of cisplatin to enter into necrotic and apoptotic cells, the viability of the PBMCs were studied by using the viSNE computational single-cell resolution plot and heat map indicating the LD mean marker counts (Fig.11F, G) [17] . The study also reported no impact of the Ti 3 C 2 T x MXene on the functionality of the CD25 or CD69 markers for PBMCs, CD4 T cells, or CD8 T cells. Whereas a significant reduction of CD69 expression was observed for the monocytes especially for intermediate monocytes with no change in CD25 expressions, indicating the reduction of proinflammatory activity of the intermediate monocytes ( Fig. 12 ) [17] . Ref. [17] , Copyright 2021, Elsevier.

The exposure of an external agent to the body results in the higher production of cytokine hormones, provoking the cytokine storm and damaging internal organs [87] . In the case of COVID-19 patients with extreme severity, there is an increased production of cytokines like TNF-α, IL-10, and IL-6, etc. which leads to the fatal condition of patients with severe damage to internal organs [87, 88] . Therefore it is crucial to remove the excess cytokines from the body in no time. To explore the impact of Ti 3 C 2 T x MXene on cytokine production, the researchers applied CyTOF to study the growth rate of IFN-ɣ, IL-17f, IL-17a, TNF-α, IL-6 cytokines as well as the Granzyme B and Perforin proteins that contribute to the immune response of cells [17] . The heat map reveals a feeble production rate of the cytokines indicating the anti-inflammatory properties of MXenes (Fig. 13 ) [17] . MXene as compared to untreated and LPS exposed cells. Reproduced with permission from

Ref. [17] , Copyright 2021, Elsevier.

To understand the inactivation mechanism of MXene towards the SARS-CoV-2 virus, Unal and his coworkers [17] conducted 

The superior antiviral activities, greater photocatalytic/photothermal properties, and excellent biocompatibility of MXenes can be utilized in an effective way to defeat the COVID-19 pandemic. Many researchers are working worldwide to combat the pandemic and the addition of MXenes in this field can lead the research a step ahead.

The disorders [92] . Better treatment can be done by utilizing the high electrical conductivity of MXenes to regenerate the neural tissues and increase neuronal electrical activities (Fig. 15 ) [93] . Studies have shown that the porous nanofiber scaffolds enhance tissue regeneration by promoting cell adhesion, cell growth, diffusion of nutrients and vascularization, etc. [94, 95] .

This porosity and high surface area of the nanofiber scaffolds can be achieved by utilizing the unique layered structure of MXenes [96] .

The COVID-19 infected patients have also reported a coinfection of bacteria and fungi in the respiratory tract, which needs antimicrobial therapy [97] . MXenes can be a potent Ref. [98] , Copyright 2020, Elsevier. 

The high aspect ratio and greater hydrophilicity of MXenes with lesser cytotoxicity provide a great promise for higher drug loading and point-specific drug delivery to the internal organs like lungs, specifically in the case of SARS-CoV-2 virus-infected patients [100] . Liu et al. [101] reported a superior drug loading capacity of 225.05% in the case of Ti 3 C 2 -cobalt nanowire heterojunction nanocarriers. The hydrogel nanocomposites of Ti 3 C 2 /polyacrylamide exhibited greater drug loading of 97.5-127.7 mg g -1 and drug release ability of 62.1%-81.4%, respectively [16] . The superior hydrophilicity of MXenes can provide a greater solubility with the body fluids and can efficiently enhance the drug uptake by body tissues [102] . Higher drug loading and facile encapsulation methods for structured drug delivery can be achieved by the tunable surface chemistry of MXenes [7, 103] . Wu et al. [104] fabricated pH/near-infrared multi-responsive microcapsules consisting of hollow hydroxyapatite, chitosan/hyaluronic acid multilayers, gold nanorods, and MXene by a layer-by-layer approach. The microcapsules were loaded with doxorubicin, which is a potential therapeutic drug against SARS-CoV-2 [105] . The fabricated microcapsules exhibited a greater drug loading capacity, distinct photothermal conversion efficiency, and biocompatibility. This property can be beneficial for remotely controlled drug delivery applications.

The hydrophilic nature and negative surface functionalization of MXenes can be combined to fabricate different biomedical instruments like biosensors, dialyzers, sterilizers, etc. COVID-19 patients under hemodialysis are more prone to infection due to the non-removal of uremic toxins from the body [106] . Meng et al. [107] reported an adsorption efficiency of up to 94%

between MXene and urea, which helps in the removal of the uremic toxins from the dialysate in the case of patients under hemodialysis. The author also observed greater urea adsorption for the Ti 3 C 2 T x MXene as compared to the Ti 2 CT x and Mo 2 TiC 2 T x MXenes and improved cell life with the exposure of MXene up to 24h, making it a suitable material for biomedical applications [107] . The paramagnetic behavior along with the high atomic number of MXenes combine to result in incomparable attenuation of X rays, which can be useful for the computed tomography (CT) scanning of the virus-affected lungs to measure the extent of infection followed by appropriate diagnosis [108] .

The excess release of cytokines in SARS-CoV-2 virus-infected patients results in cytokine release syndrome (CRS) and lymphocytic apoptosis leading to a detrimental impact on the internal organs [87] . Studies have shown improved survival of early-stage sepsis patients by the removal of cytokines from the bloodstream [109] . The porous carbon structure of MXene can be implemented to adsorb the cytokines like IL-6, IL-10, TNF-α, etc. using extracorporeal perfusion (ECP) techniques, which are the major inflammatory factors in COVID-19 patients [96, 110] . Wang et al. [23] used Ti 3 C 2 T x MXene nanosheet as an absorbent in the hemoperfusion therapy to remove cytokine from the blood of COVID-19 patients (Fig. 18 ).

They found that MXene sheets have efficient removal capacities of the cytokines like IL-6, which is approximately 13.4% higher than the conventional activated carbon absorbents.

Molecular-level analysis revealed that the hydrogen bonding between IL-6 and MXene nanosheets promotes absorption and the transformation of the secondary structure of IL-6 from α-helix to -sheet results in their immobilization. The authors also observed greater blood compatibility with no side effects on the human blood composition. MXenes show a great promise for biosensing activities because of their excellent physicochemical properties, greater active sites provided by enriched surface termination groups that can immobilize the biomolecules, admirable electrocatalytic activity, and enhanced enzyme loading capacity provided by the larger specific surface area of the multi-layered structure, and superior biocompatibility, etc [111, 112] . Most of the patients affected by COVID-19 are found to be asymptomatic, which is a major reason for the faster spreading of the disease [113] . Therefore, early detection and diagnosis are the keys to preventing new infections. The MXene-based biosensors can play an effective role in the detection of biomarkers without any invasive methods [112] . Li et al. [19] fabricated an MXene-graphene Due to the lower mutation rate of nucleocapsid genomes over spike genomes, most of the national RTPCR protocols target the nucleocapsid gene for accurate detection of SARS-CoV-2 [114] . However, gene detection using RTPCR requires a tedious process of sample preparation, high-cost fluorescent probes, and a long processing time, which is not able to cope with the sudden outbreak of the pandemic. Therefore, fast and accurate detection is the need of the hour. Chen et al. [115] fabricated a single-stranded DNA (ssDNA)/ Ti 3 C 2 T x biosensor by the surface functionalization of ssDNA probes on Ti 3 C 2 T x films through noncovalent adsorption. The hybridization of the ssDNA probe with the SARS-CoV-2 nucleocapsid gene results in the detachment of double strained DNA from the Ti 3 C 2 T x surface, contributing to an enhanced channel conductivity (Fig. 19 ). The ssDNA/ Ti 3 C 2 T x biosensor exhibited a low limit of detection of ~10 5 copies/mL in saliva with a faster response. The authors also claimed that the self-collected saliva samples are less invasive, can reduce healthcare worker exposure, and eliminate the need for sample collecting tools like swabs. Liu et al. [111] fabricated MXene based microfluidic biosensor chip with a combined effect of dialysis and subsequent detection of urea, uric acid, and creatinine biomarkers in the blood sample, which can help to reduce the fatality of kidney affected COVID-19 patients [106] .

Studies have shown a greater rate of COVID-19 mortality in the case of patients having comorbidities, and diabetes is one of them, which reported a two-fold fatality rate [116] . The efficient and timely detection of blood glucose levels by the MXene-based glucose sensors can help to reduce the mortality rate to a greater extent [117] . Rakhi et al. [118] fabricated GO x /Au/MXene/Nafion/GCE composite glucose detection biosensors having superior stability, repeatability, and reproducibility. In the glucose concentration range of 0.1 to 18 mM, the biosensor exhibited a linear amperometric response with a detection limit of 5.9 µM and greater sensitivity of 4.2 µAmM -1 respectively [118] . Lei 

Over the last few years, researchers have successfully synthesized low density, porous, and lightweight MXene foams having superior properties for biomedical applications [125] . The lightweight and porous MXene foams can fit into the requirement for pure air due to their particulate filtration properties. This particularly has a greater need in this COVID-19

pandemic situation due to the high dependence on face masks that prevents virus contaminations [126] . Although the face masks work as a virus shield, once the viruses get stuck in the outer layer of the face mask, it remains active for a longer period. Hence, proper handling and disposal of face masks have become a critical need. The major benefit of the MXene foam-based face masks is that they not only adhere to the viruses but also inactivate them by their antiviral properties [112] . Similar virus inactivation and safety methods can be achieved by the coating of MXene on PPE kits and other medical devices. These MXene based face masks, PPE kits, face shields, etc. can help to bring down the infection rate, mostly caused by COVID-19 infected asymptomatic persons [127] . Along with this, the flexibility and transparency of MXenes can also be utilized to fabricate flexible and transparent medical spectacles, face shields, etc. with antiviral properties [128] . 

MXenes can be a prospective material for the prevention and diagnosis of the COVID- MXene coated antiviral face masks, PPE kits, and biomedical instruments has been done on the laboratory scale but still, it is not commercialized due to the issues of durability, scalability, and cost-effectiveness. Therefore low-cost and high-yield green synthesis approach has to be discovered for the scalable synthesis of MXenes and their nanocomposites. Efficient synthesis methods to increase the interlayer space and surface area of MXene can expose more active sites for viral inactivation. The adhesion of MXenes, when applied as a coating on metals and polymer surfaces is still one of the primary difficulties that have to be addressed. As in the future, many pandemics will grasp the world due to extreme environmental degradation, researchers should get ready to face those with their incredible innovations on antiviral MXene.

Not only the innovations but also the transition of MXene antiviral therapy from bench to bedsides is highly required. 

Authors declare no conflict of interest.

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Role of metal and metal oxide nanoparticles as diagnostic and therapeutic tools for highly prevalent viral infections

Toward nanotechnology-enabled approaches against the COVID-19 pandemic

SARS-CoV-2 vaccines: status report

Nanotechnology for protein delivery: Overview and perspectives

Smart and Sustainable Nanotechnological Solutions in a Battle against COVID-19 and Beyond: A Critical Review

Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19

Assembly of MXene/PP separator and its enhancement for Ni-Rich LiNi0. 8Co0. 1Mn0. 1O2 electrochemical performance

State of the art recent progress in MXene-based photocatalysts: a comprehensive review

Two-dimensional MXenebased materials for photothermal therapy

State of the art recent progress in two dimensional MXenes based gas sensors and biosensors: A comprehensive review

Fabrication of novel MXene (Ti 3 C 2)/polyacrylamide nanocomposite hydrogels with enhanced mechanical and drug release properties

2D MXenes with antiviral and immunomodulatory properties: A pilot study against SARS-CoV-2

Rapid detection of COVID-19 causative virus (SARS-CoV-2) in human nasopharyngeal swab specimens using field-effect transistor-based biosensor

MXene-graphene field-effect transistor sensing of influenza virus and SARS-CoV-2

Two-dimensional material-based biosensors for virus detection

Ultrasensitive monolayer MoS2 field-effect transistor based DNA sensors for screening of down syndrome

Metallic Ti3C2T x MXene gas sensors with ultrahigh signal-tonoise ratio

Ultraefficiently Calming Cytokine Storm Using Ti3C2Tx MXene

2D metal carbides and nitrides (MXenes)

Synthesis of Mo4VAlC4 MAX phase and two-dimensional Mo4VC4 MXene with five atomic layers of transition metals

MXene based emerging materials for supercapacitor applications: Recent advances, challenges, and future perspectives

Double transition-metal MXenes: Atomistic design of two-dimensional carbides and nitrides

Ten Years of Progress in the Synthesis and Development of MXenes

Two-dimensional transition metal carbides

MXenes-A new class of 2D layered materials: Synthesis, properties, applications as supercapacitor electrode and beyond

Synthesis, structure, properties and applications of MXenes: Current status and perspectives

A two-dimensional lamellar membrane: MXene nanosheet stacks

Potential environmental applications of MXenes: A critical review

2D MXenes for electromagnetic shielding: a review

MXene and MXene-based composites: synthesis, properties and environment-related applications

Intercalation and delamination of layered carbides and carbonitrides

Complexity of intercalation in MXenes: Destabilization of urea by two-dimensional titanium carbide

Amine-assisted delamination of Nb2C MXene for Li-ion energy storage devices

The effect of hydrazine intercalation on the structure and capacitance of 2D titanium carbide (MXene)

Large-scale delamination of multilayers transition metal carbides and carbonitrides "MXenes

Guidelines for synthesis and processing of two-dimensional titanium carbide (Ti3C2T x MXene)

Surface modified MXene Ti3C2 multilayers by aryl diazonium salts leading to large-scale delamination

Cation intercalation and high volumetric capacitance of two-dimensional titanium carbide

Two-dimensional nanocrystals produced by exfoliation of Ti3AlC2

OH-terminated twodimensional transition metal carbides and nitrides as ultralow work function materials

Conductive twodimensional titanium carbide 'clay'with high volumetric capacitance

Synthesis and characterization of 2D molybdenum carbide (MXene)

Preparation of high-purity V2C MXene and electrochemical properties as Li-ion batteries

Environmental friendly scalable production of colloidal 2D titanium carbonitride MXene with minimized nanosheets restacking for excellent cycle life lithium-ion batteries

Synthesis of two-dimensional Ti3C2Tx MXene using HCl+ LiF etchant: enhanced exfoliation and delamination

Effective removal of U (VI) and Eu (III) by carboxyl functionalized MXene nanosheets

Transparent conductive two-dimensional titanium carbide epitaxial thin films

Ti 3 C 2 T x (MXene)-polyacrylamide nanocomposite films

Large-area high-quality 2D ultrathin Mo 2 C superconducting crystals

Ultrathin N-doped Mo2C nanosheets with exposed active sites as efficient electrocatalyst for hydrogen evolution reactions

Plasmaenhanced pulsed-laser deposition of single-crystalline M o 2 C ultrathin superconducting films

Advances in the synthesis of 2D

A review on coronavirus survivability on material's surfaces: present research scenarios, technologies and future directions

Coronaviruses: an overview of their replication and pathogenesis

The severe acute respiratory syndrome

A decade after SARS: strategies for controlling emerging coronaviruses

Novel Coronavirus (2019-nCoV) situation reports

-ncov)-situation-reports

Consequences of Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Genome in Comparison to Other Pathogenic Coronaviruses

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide

Atomistic simulation reveals structural mechanisms underlying D614G spike glycoprotein-enhanced fitness in SARS-COV-2

Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus

Structural and functional basis of SARS-CoV-2 entry by using human ACE2

COVID-19: a new virus, but a familiar receptor and cytokine release syndrome

Photodynamic therapy for COVID-19

Effect of glycine functionalization of 2D titanium carbide (MXene) on charge storage

In-silico study on viability of MXenes in suppressing the coronavirus infection and distribution

Physical properties of 2D MXenes: from a theoretical perspective

Effect of ambient temperature on COVID-19 infection rate

Stability and inactivation of SARS coronavirus

MXene Ti3C2: an effective 2D light-to-heat conversion material

Theranostic 2D tantalum carbide (MXene)

Nano antiviral photodynamic therapy: A probable biophysicochemical management modality in SARS-CoV-2

The theranostic nanoagent Mo 2 C for multi-modal imaging-guided cancer synergistic phototherapy

Progress and biomedical applications of MXenes

Ecotoxicological assessment of Ti 3 C 2 T x (MXene) using a zebrafish embryo model

MXene nanosheets may induce toxic effect on the early stage of embryogenesis

2D ultrathin MXene-based drug-delivery nanoplatform for synergistic photothermal ablation and chemotherapy of cancer

A two-dimensional biodegradable niobium carbide (MXene) for photothermal tumor eradication in NIR-I and NIR-II biowindows

Biocompatible 2D titanium carbide (MXenes) composite nanosheets for pH-responsive MRI-guided tumor hyperthermia

COVID-19: consider cytokine storm syndromes and immunosuppression

Clinical and immunological features of severe and moderate coronavirus disease

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

Subcellular hot spots of GPCR signaling promote vascular inflammation

Decoding SARS-CoV-2 hijacking of host mitochondria in COVID-19 pathogenesis

The clinical spectrum of encephalitis in COVID-19 disease: the ENCOVID multicentre study

2D Ti3C2TxMXene couples electrical stimulation to promote proliferation and neural differentiation of neural stem cells

Putting electrospun nanofibers to work for biomedical research

Scaffolds and cells for tissue regeneration: different scaffold pore sizes-different cell effects

A mini-review of MXene porous films: Preparation, mechanism and application

Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing

Synthesis, characterization and antifungal property of Ti3C2Tx MXene nanosheets

Antimicrobial modeof-action of colloidal Ti3C2Tx MXene nanosheets

Recent development and prospects of surface modification and biomedical applications of MXenes

MXene/cobalt nanowire heterojunction for controlled drug delivery and chemophotothermal therapy

Recent progress on synthesis, structure and electrocatalytic applications of MXenes

The world of two-dimensional carbides and nitrides (MXenes), Science (80-. )

Chitosan/hyaluronic acid based hollow microcapsules equipped with MXene/gold nanorods for synergistically enhanced near infrared responsive drug delivery

Identification of doxorubicin as a potential therapeutic against SARS-CoV-2 (COVID-19) protease: a molecular docking and dynamics simulation studies

The novel coronavirus 2019 epidemic and kidneys

MXene sorbents for removal of urea from dialysate: A step toward the wearable artificial kidney

Chemistry of two-dimensional MXene nanosheets in theranostic nanomedicine

Cytokine blood filtration responses in COVID-19

Hierarchical porous carbide-derived carbons for the removal of cytokines from blood plasma

MXene-enabled electrochemical microfluidic biosensor: applications toward multicomponent continuous monitoring in whole blood

Emergent 2D materials for combating infectious diseases: the potential of MXenes and MXene-graphene composites to fight against pandemics

Mathematical modeling of COVID-19 spreading with asymptomatic infected and interacting peoples

Multicentre comparison of quantitative PCR-based assays to detect SARS-CoV-2

DNA-Functionalized Ti3C2T x MXenes for Selective and Rapid Detection of SARS

Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis

Recent advances in MXene-based electrochemical sensors and biosensors

Novel amperometric glucose biosensor based on MXene nanocomposite

A MXene-based wearable biosensor system for high-performance in vitro perspiration analysis

MXene-functionalised 3D-printed electrodes for electrochemical capacitors

Sudden cardiac death in COVID-19 patients, a report of three cases

Chemiluminescence immunoassays for simultaneous detection of three heart disease biomarkers using magnetic carbon composites and three-dimensional microfluidic paper-based device

The TDs/aptamer cTnI biosensors based on HCR and Au/Ti3C2-MXene amplification for screening serious patient in COVID-19 pandemic

Ultrathin Ti3C2 nanosheets based "off-on" fluorescent nanoprobe for rapid and sensitive detection of HPV infection

Highly Stable 3D Ti3C2T x MXene-Based Foam Architectures toward High-Performance Terahertz Radiation Shielding

Face masks and respirators in the fight against the COVID-19 pandemic: A review of current materials, advances and future perspectives

Proportion of asymptomatic infection among COVID-19 positive persons and their transmission potential: A systematic review and meta-analysis

Polymer-Laminated Ti3C2TX MXene Electrodes for Transparent and Flexible Field-Driven Electronics

3D printing of freestanding MXene architectures for current-collector-free supercapacitors