Current Advances in Nanomaterial-associated Micro and Nano-devices for SARS-CoV-2 Detection

COVID-19 spread rapidly around the world in 18 months, with various forms of variants caused by severe acute respiratory syndrome (SARS-CoV). This has put pressure on the world community and created an urgent need for understanding its early occurrence through rapid, simple, cheap, and yet highly accurate diagnosis. The most widely adopted method as of today is the real-time reverse-transcriptase polymerase chain reaction. This test has shown the potential for rapid testing, but unfortunately, the test is not rapid and, in some cases, displays false negatives or false positives. The nanomaterials play an important role in creating highly sensitive systems, and have been thought to significantly improve the performance of the SARSCoV- 2 protocols. Several biosensors based on micro-and nano-sensors for SARS-CoV-2 detection have been reported, and they employ multi-dimensional hybrids on sensing surfaces with devices having different sizes and geometries. Zero-to-three-dimension nanomaterial hybrids on sensing surfaces, including nanofilm hybrids for SARS-CoV-2 detection, were employed with unprecedented sensitivity and accuracy. Furthermore, the sensors were nanofluidic and mediated high-performance SARS-CoV-2 detection. This breakthrough has brought the possibility of making a biosystem on a chip (Bio-SoC) for rapid, cheap, and point-of-care detection. This review summarises various advancements in nanomaterial-associated nanodevices and metasurface devices for detecting SARS-CoV-2.

Phytochemicals of Withania somnifera as a Future Promising Drug against SARS-CoV-2: Pharmacological Role, Molecular Mechanism, Molecular Docking Evaluation, and Efficient Delivery.

Coronavirus disease (COVID-19) has killed millions of people since first reported in Wuhan, China, in December 2019. Intriguingly, Withania somnifera (WS) has shown promising antiviral effects against numerous viral infections, including SARS-CoV and SARS-CoV-2, which are contributed by its phytochemicals. This review focused on the updated testing of therapeutic efficacy and associated molecular mechanisms of WS extracts and their phytochemicals against SARS-CoV-2 infection in preclinical and clinical studies with the aim to develop a long-term solution against COVID-19. It also deciphered the current use of the in silico molecular docking approach in developing potential inhibitors from WS targeting SARS-CoV-2 and host cell receptors that may aid the development of targeted therapy against SARS-CoV-2 ranging from prior to viral entry until acute respiratory distress syndrome (ARDS). This review also discussed nanoformulations or nanocarriers in achieving effective WS delivery to enhance its bioavailability and therapeutic efficacy, consequently preventing the emergence of drug resistance, and eventually therapeutic failure.

Nanodiamond conjugated SARS-CoV-2 spike protein: electrochemical impedance immunosensing on a gold microelectrode.

A promising immunosensing strategy in diagnosing SARS-CoV-2 is proposed using a 10-µm gap-sized gold interdigitated electrode (AuIDE) to target the surface spike protein (SP). The microelectrode surface was modified by (3-glycidyloxypropyl) trimethoxysilane to enforce the epoxy matrix, which facilitates the immobilization of the anti-SP antibody. The immunosensing performance was evaluated by integrating a nanosized (~ 10 nm) diamond-complexed SP as a target. The proposed immunoassay was quantitatively evaluated through electrochemical impedance spectroscopy (EIS) with the swept frequency from 0.1 to 1 MHz using a 100 mVRMS AC voltage supply. The immunoassay performed without diamond integration showed low sensitivity, with the lowest SP concentration measured at 1 pM at a determination coefficient of R2 = 0.9681. In contrast, the nanodiamond-conjugated SP on the immunosensor showed excellent sensitivity with a determination coefficient of R2 = 0.986. SP detection with a nanodiamond-conjugated target on AuIDE reached the low limit of detection at 189 fM in a linear detection range from 250 to 8000 fM. The specificity of the developed immunosensor was evaluated by interacting influenza-hemagglutinin and SARS-CoV-2-nucleocapsid protein with anti-SP. In addition, the authentic interaction of SP and anti-SP was validated by enzyme-linked immunosorbent assay.

Nanosensors: Recent Perspectives on Attainments and Future Promise of Downstream Applications

Nano Sensors are sensing devices with a dimension of less than or equal to 100nm. They are incredibly tiny devices that transform physical, chemical, or biological substances into detectable signals. Because of this device's capacity to detect physical and chemical changes, nanotechnology has emerged as a technology of choice in a variety of industries. The device provides efficient and cost-effective methods for detecting and measuring chemical and physical characteristics. This overview discusses the status of Nano Sensors, as well as their accomplishments and potential applications toward downstream targets in medical, security, agriculture as well in Covid-19 detection. The paper provides a summary and critical analysis of various architectures (structures) employed in the development and use of Nano Sensors. Surface engineering is used to generate diverse chemistries for both general and specialised purposes. We derived fresh findings from available data on the mechanism, prospective development of various structures, approaches, and applications, and highlighted the contrasts and similarities in their characteristics and working processes. The review further summarized ability and future expected of this sensor in dealing with the various challenges where different nano sensors, types, fabrication techniques and applications with highlighted novelties of these techniques and applications are presented.

Biosensing epidemic and pandemic respiratory viruses: Internet of Things with Gaussian noise channel algorithmic model.

The current world condition is dire due to epidemics and pandemics as a result of novel viruses, such as influenza and the coronavirus, causing acute respiratory syndrome. To overcome these critical situations, the current research seeks to generate a common surveillance system with the assistance of a controlled Internet of Things operated under a Gaussian noise channel. To create the model system, a study with an analysis of H1N1 influenza virus determination on an interdigitated electrode (IDE) sensor was validated by current-volt measurements. The preliminary data were generated using hemagglutinin as the target against gold-conjugated aptamer/antibody as the probe, with the transmission pattern showing consistency with the Gaussian noise channel algorithm. A good fit with the algorithmic values was found, displaying a similar pattern to that output from the IDE, indicating reliability. This study can be a model for the surveillance of varied pathogens, including the emergence and reemergence of novel strains.

Aptasensing nucleocapsid protein on nanodiamond assembled gold interdigitated electrodes for impedimetric SARS-CoV-2 infectious disease assessment.

In an aim of developing portable biosensor for SARS-CoV-2 pandemic, which facilitates the point-of-care aptasensing, a strategy using 10 µm gap-sized gold interdigitated electrode (AuIDE) is presented. The silane-modified AuIDE surface was deposited with ∼20 nm diamond and enhanced the detection of SARS-CoV-2 nucleocapsid protein (NCP). The characteristics of chemically modified diamond were evidenced by structural analyses, revealing the cubic crystalline nature at (220) and (111) planes as observed by XRD. XPS analysis denotes a strong interaction of carbon element, composed ∼95% as seen in EDS analysis. The C-C, CC, CO, CN functional groups were well-refuted from XPS spectra of carbon and oxygen elements in diamond. The interrelation between elements through FTIR analysis indicates major intrinsic bondings at 2687-2031 cm-1. The aptasensing was evaluated through electrochemical impedance spectroscopy measurements, using NCP spiked human serum. With a good selectivity the lower detection limit was evidenced as 0.389 fM, at a linear detection range from 1 fM to 100 pM. The stability, and reusability of the aptasensor were demonstrated, showing ∼30% and ∼33% loss of active state, respectively, after ∼11 days. The detection of NCP was evaluated by comparing anti-NCP aptamer and antibody as the bioprobes. The determination coefficients of R2 = 0.9759 and R2 = 0.9772 were obtained for aptamer- and antibody-based sensing, respectively. Moreover, the genuine interaction of NCP aptamer and protein was validated by enzyme linked apta-sorbent assay. The aptasensing strategy proposed with AuIDE/diamond enhanced sensing platform is highly recommended for early diagnosis of SARS-CoV-2 infection.

SARS-CoV-2 spike protein: Site-specific breakpoints for the development of COVID-19 vaccines.

SARS-CoV2 is a member of human coronaviruses and is the causative agent of the present pandemic COVID-19 virus. In order to control COVID-19, studies on viral structure and mechanism of infectivity and pathogenicity are sorely needed. The spike (S) protein is comprised of S1 & S2 subunits. These spike protein subunits enable viral attachment by binding to the host cell via ACE-2 (angiotensin converting enzyme-2) receptor, thus facilitating the infection. During viral entry, one of the key steps is the cleavage of the S1-S2 spike protein subunits via surface TMPRSS2 (transmembrane protease serine 2) and results in viral infection. Hence, the S-protein is critical for the viral attachment and penetration into the host. The rapid advancement of our knowledge on the structural and functional aspects of the spike protein could lead to development of numerous candidate vaccines against SARS-CoV2. Here the authors discuss about the structure of spike protein and explore its related functions. Our aim is to provide a better understanding that may aid in fighting against CoVID-19 and its treatment.

MicroRNA of N-region from SARS-CoV-2: Potential sensing components for biosensor development.

An oligonucleotide DNA probe has been developed for the application in the DNA electrochemical biosensor for the early diagnosis of coronavirus disease (COVID-19). Here, the virus microRNA from the N-gene of severe acute respiratory syndrome-2 (SARS-CoV-2) was used for the first time as a specific target for detecting the virus and became a framework for developing the complementary DNA probe. The sequence analysis of the virus microRNA was carried out using bioinformatics tools including basic local alignment search tools, multiple sequence alignment from CLUSTLW, microRNA database (miRbase), microRNA target database, and gene analysis. Cross-validation of distinct strains of coronavirus and human microRNA sequences was completed to validate the percentage of identical and consent regions. The percent identity parameter from the bioinformatics tools revealed the virus microRNAs' sequence has a 100% match with the genome of SARS-CoV-2 compared with other coronavirus strains, hence improving the selectivity of the complementary DNA probe. The 30 mer with 53.0% GC content of complementary DNA probe 5' GCC TGA GTT GAG TCA GCA CTG CTC ATG GAT 3' was designed and could be used as a bioreceptor for the biosensor development in the clinical and environmental diagnosis of COVID-19.

Infection-Mediated Clinical Biomarkers for a COVID-19 Electrical Biosensing Platform.

The race towards the development of user-friendly, portable, fast-detection, and low-cost devices for healthcare systems has become the focus of effective screening efforts since the pandemic attack in December 2019, which is known as the coronavirus disease 2019 (COVID-19) pandemic. Currently existing techniques such as RT-PCR, antigen-antibody-based detection, and CT scans are prompt solutions for diagnosing infected patients. However, the limitations of currently available indicators have enticed researchers to search for adjunct or additional solutions for COVID-19 diagnosis. Meanwhile, identifying biomarkers or indicators is necessary for understanding the severity of the disease and aids in developing efficient drugs and vaccines. Therefore, clinical studies on infected patients revealed that infection-mediated clinical biomarkers, especially pro-inflammatory cytokines and acute phase proteins, are highly associated with COVID-19. These biomarkers are undermined or overlooked in the context of diagnosis and prognosis evaluation of infected patients. Hence, this review discusses the potential implementation of these biomarkers for COVID-19 electrical biosensing platforms. The secretion range for each biomarker is reviewed based on clinical studies. Currently available electrical biosensors comprising electrochemical and electronic biosensors associated with these biomarkers are discussed, and insights into the use of infection-mediated clinical biomarkers as prognostic and adjunct diagnostic indicators in developing an electrical-based COVID-19 biosensor are provided.