Graphene-Based Electrochemical Nano-Biosensors for Detection of SARS-CoV-2

COVID-19, a viral respiratory illness, is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), which was first identified in Wuhan, China, in 2019 and rapidly spread worldwide. Testing and isolation were essential to control the virus's transmission due to the severity of the disease. In this context, there is a global interest in the feasibility of employing nano-biosensors, especially those using graphene as a key material, for the real-time detection of the virus. The exceptional properties of graphene and the outstanding performance of nano-biosensors in identifying various viruses prompted a feasibility check on this technology. This paper focuses on the recent advances in using graphene-based electrochemical biosensors for sensing the SARS-CoV-2 virus. Specifically, it reviews various types of electrochemical biosensors, including amperometric, potentiometric, and impedimetric biosensors, and discusses the current challenges associated with biosensors for SARS-CoV-2 detection. The conclusion of this review discusses future directions in the field of electrochemical biosensors for SARS-CoV-2 detection, underscoring the importance of continued research and development in this domain.

On a Novel Dynamics of a SIVR Model Using a Laplace Adomian Decomposition Based on a Vaccination Strategy

In this paper, we introduce a SIVR model using the Laplace Adomian decomposition. This model focuses on a new trend in mathematical epidemiology dedicated to studying the characteristics of vaccination of infected communities. We analyze the epidemiological parameters using equilibrium stability and numerical analysis techniques. New mathematical strategies are also applied to establish our epidemic model, which is a pandemic model as well. In addition, we mathematically establish the chance for the next wave of any pandemic disease and show that a consistent vaccination strategy could control it. Our proposal is the first model introducing a vaccination strategy to actively infected cases. We are sure this work will serve as the basis for future research on COVID-19 and pandemic diseases since our study also considers the vaccinated population. © 2023 by the authors.

Design of a Tuned Proportional-Integral-Derivative Water Level Controller for First-Order Automated Irrigation System in Rice Field

Some problems of Filipino farmers in Nueva Ecija are irrigation systems and labor shortage. Most of them are unable to work due to old age while others chose to stop because of the COVID-19 pandemic. Meanwhile, irrigation systems have been an issue due to the lack of resources such as continuous water supply and control. Fortunately, there is a progression of smart farming in the country which could assist in optimizing farming processes. This study presents a systematic literature survey on rice farming technologies and challenges. This study also aims to help address these problems by creating a rice irrigation system that introduces a water level control system. The system was comprised of a mobile application, Arduino ESP32 module, and a tank with water level sensors. The mobile application was used to set the desired water level while the proportional- integral-derivative (PID) controller adjusted the water level automatically. When current water level is lower than the setpoint, the valves to the tank will open. Tank specifications were used to come up with a transfer function for the system. The proposed design was simulated in MATLAB Simulink and PID parameters were tuned to enhance system performance. The tuned control system obtained an output response with less overshoot and faster settling time. © 2022 IEEE.

Analytics, Properties and Applications of Biologically Active Stilbene Derivatives.

Stilbene and its derivatives belong to the group of biologically active compounds. Some derivatives occur naturally in various plant species, while others are obtained by synthesis. Resveratrol is one of the best-known stilbene derivatives. Many stilbene derivatives exhibit antimicrobial, antifungal or anticancer properties. A thorough understanding of the properties of this group of biologically active compounds, and the development of their analytics from various matrices, will allow for a wider range of applications. This information is particularly important in the era of increasing incidence of various diseases hitherto unknown, including COVID-19, which is still present in our population. The purpose of this study was to summarize information on the qualitative and quantitative analysis of stilbene derivatives, their biological activity, potential applications as preservatives, antiseptics and disinfectants, and stability analysis in various matrices. Optimal conditions for the analysis of the stilbene derivatives in question were developed using the isotachophoresis technique.

Experimental (FT-Raman, FT-IR and NMR) and theoretical (DFT) calculations, thermodynamic parameters, molecular docking and NLO (non-linear optical) properties of N-(2,6-dimethylphenyl)-1-piperazineacetamide

Theoretical and experimental studies are performed on the new organic-inorganic hybrid molecule N-(2,6-dimethylphenyl)-1-piperazineacetamide. The vibrational spectra of the molecule are characterized using FT-IR and FT-Raman in the range 4000-600 cm(-1) and 4000-100 cm(-1), respectively. Density functional theory with B3LYP/3-21G and B3LYP/cc-pVDZ basis sets is used to calculate energy, geometrical structure, and vibrational modes of stretching, bending, and torsion. The VEDA software Autodock Vina revealed a good binding is employed to calculate the detailed vibrational assignments. The theoretical and experimental vibrational data are compared to support the present study. Density functional theory is used to calculate thermodynamic parameters (heat capacity, entropy, and enthalpy) and nonlinear optical properties. The software Gaussian09W and Gaussview 6.0 are used for theoretical calculations. Molecular docking studies are carried out to investigate the effect of the titled molecule against various proteins such as SARS-CoV-2 that affect the immune system in humans. Chemical shifts are identified using carbon and proton NMR. Non-covalent interactions are studied using a reduced density gradient. The chemical reactivity and selectivity for a local reactivity site are analyzed with the help of Fukui functions.

"Y-type” PEG modified liposomes could eliminate the accelerated blood clearance (ABC) phenomenon and improved tumor therapy

Poly(ethylene glycol) (PEG) is widely applied to decorate nanocarriers due to its "long circulation” characteristics. However, the applications of linear PEG-modified nanocarriers have been hindered by severe adverse effects due to the accelerated blood clearance (ABC) phenomenon. It was universally known that anti-PEG antibodies (APAs) were main culprits in ABC phenomenon which induced the significant change in pharmacokinetics, biological distributions of the second injection and triggered complement activation-related pseudoallergies (CARPA). Recent studies have illustrated that APAs triggered the ABC phenomenon of PEGylated protein drug and even related to the CARPA of COVID-19 vaccine. Therefore, it is urgent to inhibit the generation of APAs and eliminate the ABC phenomenon. Here, "Y-type” PEG was chosen to replace linear PEG due to its weak immunogenicity. "Y-type” PEG-lipid derivatives [DSPE-mPEG2,n (n = 2, 10, and 20 kDa)]-modified doxorubicin liposomes (DOX-PL2,n) and topotecan liposomes (TP-PL2,n) induced lower levels of APAs and could avoid activating complement system. In further research, we found that liposomes decorated with DSPE-mPEG2,n could avoid the ABC phenomenon after duplicate injections. Furthermore, pharmacodynamic tests indicated that DOX-PL2,n and TP-PL2,n improved the curative effect of S180 tumor than DOX-PL2k and TP-PL2k (linear PEGylated liposomes). For the first time, DOX-PL2,n and TP-PL2,n were used for in vivo pharmacokinetic and pharmacodynamic experiments. Liposomes ornamented with "Y-type” PEG may provide new approaches to maintaining long blood circulation time, eliminating the ABC phenomenon of encapsulated active compounds, and also could weaken CARPA and improve tumor therapeutic effect. Our research aims to promote the research and development of "Y-type” PEG-decorated nanocarriers and provide a substantial academic basis for its clinical application.

Synthesis and Virtual Screening of Pyrazolothiazole Conjugates as Promising SARS-CoV-2 Inhibitors

The current coronavirus outbreak has highlighted the significance of continuing to develop novel antiviral agents. The SARS-CoV-2 main protease (M-pro), essential for virus replication, has been recognized as a potential target for developing novel COVID-19 therapeutics. Herein, we report synthesizing a series of pyrazolothiazole conjugates and in silico molecular docking screening of their interactions with the COVID-19 protease 6LU7 protein. The new hybrids were obtained by condensing substituted pyrazole-4-carbaldehyde with N-phenyl-hydrazinecarbothioamide and subsequent refluxing with selected alpha-haloketones in a basic medium. The structures of the novel pyrazolothiazoles were fully verified by FTIR, H-1 NMR, C-13 NMR, and elemental analyses. Molecular docking and free energy analyses using the MM/GBSA approach revealed that 5 a-c and 7 a-c formed stable interactions within the protease 6LU7 pocket, thus, could be potential inhibitors of SARS-CoV-2.

Chalcone-based Ferrocenyl-Derivatives as an Antimicrobial Drug

The lack of development of new antibiotics is the major concern at the present scenario. One key factor contributing to the rise of antibiotic-resistant bacteria is the widespread movement of people throughout the world. The world has seen the consequences of the migration in the case of COVID-19 very recently. To tackle or cope with the situation, development of new antibiotics is very essential, which can be inhibited multidrug-resistant bacteria. In this framework, chalcone-based ferrocenyl containing compounds showed a diversity of pharmacological properties and its derivatives possess a high degree of structural diversity and it is helpful for the discovery of new therapeutic agents. Thus, there is a need for new antibacterial drug candidates with increased strength, new targets, low cost, superior pharmacokinetic properties and minimum side effects. The present review concluded and focuses on the recent developments in the area of medicinal chemistry to explore the diverse chemical structures of potent antibacterial agents and also describes its structure-activity relationship studies (SAR). This review will help to the researchers in the medical field to find out the future generation potential drug discovery and development. © 2023 Chemical Publishing Co.. All rights reserved.

Blackwater Fever Treated with Steroids in Nonimmune Patient, Italy.

Causes of blackwater fever, a complication of malaria treatment, are not completely clear, and immune mechanisms might be involved. Clinical management is not standardized. We describe an episode of blackwater fever in a nonimmune 12-year-old girl in Italy who was treated with steroids, resulting in a rapid clinical resolution.

Different In Silico Approaches Using Heterocyclic Derivatives against the Binding between Different Lineages of SARS-CoV-2 and ACE2.

Over the last few years, the study of the SARS-CoV-2 spike protein and its mutations has become essential in understanding how it interacts with human host receptors. Since the crystallized structure of the spike protein bound to the angiotensin-converting enzyme 2 (ACE2) receptor was released (PDB code 6M0J), in silico studies have been performed to understand the interactions between these two proteins. Specifically, in this study, heterocyclic compounds with different chemical characteristics were examined to highlight the possibility of interaction with the spike protein and the disruption of the interaction between ACE2 and the spike protein. Our results showed that these compounds interacted with the spike protein and interposed in the interaction zone with ACE2. Although further studies are needed, this work points to these heterocyclic push-pull compounds as possible agents capable of interacting with the spike protein, with the potential for the inhibition of spike protein-ACE2 binding.

Investigating the novel acetonitrile derivatives as potential SARS-CoV-2 main protease inhibitor using molecular modeling approach.

The COVID-19 is declared a pandemic by World Health Organization (WHO). It causes respiratory illness which leads to oxygen deficiency; it has affected millions of lives all around the globe. It has also been observed that people with diabetes condition are more likely to have severe symptoms when infected with the SARS-CoV2. So, continued efforts are being taken to design and discover potential anti-covid drugs. Earlier, a study reveals that the acetonitrile (2-phenyl-4H-benzopyrimedo [2,1-b]-thiazol-4-yliden) derivatives have potential anti-diabetic activity. Hence, drugs repurpose approach was used to identify the potential acetonitrile derivative targeting the main protease of SARS-CoV2. Here, ADMET, molecular docking, and molecular dynamics simulation techniques were employed, to identify potential acetonitrile compounds against the main protease. The acetonitrile compounds (A to M) show the drug-likeness properties. Next, the molecular docking and dynamics simulation study reveals that acetonitrile compounds A, F, G, and L show a higher binding affinity and have an effect on the structure and dynamics of the main protease. Furthermore, binding energy calculations reveal that the acetonitrile derivative F has a higher binding affinity with the main protease and derivative L has a lower binding affinity with the main protease. The binding affinity of acetonitrile derivatives decreases in the order of F > A > G > L with the main protease. Thus, our computational modeling study provides valuable structural and energetic information of interaction of potential acetonitrile derivatives with the main protease which could be further used as potential lead molecules against the SARS-CoV2.Communicated by Ramaswamy H. Sarma.

Amentoflavone derivatives significantly act towards the main protease (3CLPRO/MPRO) of SARS-CoV-2: in silico admet profiling, molecular docking, molecular dynamics simulation, network pharmacology.

SARS-CoV-2 is the foremost culprit of the novel coronavirus disease 2019 (nCoV-19 and/or simply COVID-19) and poses a threat to the continued life of humans on the planet and create pandemic issue globally. The 3-chymotrypsin-like protease (MPRO or 3CLPRO) is the crucial protease enzyme of SARS-CoV-2, which directly involves the processing and release of translated non-structural proteins (nsps), and therefore involves the development of virus pathogenesis along with outbreak the forecasting of COVID-19 symptoms. Moreover, SARS-CoV-2 infections can be inhibited by plant-derived chemicals like amentoflavone derivatives, which could be used to develop an anti-COVID-19 drug. Our research study is designed to conduct an in silico analysis on derivatives of amentoflavone (isoginkgetin, putraflavone, 4''''''-methylamentoflavone, bilobetin, ginkgetin, sotetsuflavone, sequoiaflavone, heveaflavone, kayaflavone, and sciadopitysin) for targeting the non-structural protein of SARS-CoV-2, and subsequently further validate to confirm their antiviral ability. To conduct all the in silico experiments with the derivatives of amentoflavone against the MPRO protein, both computerized tools and online servers were applied; notably the software used is UCSF Chimera (version 1.14), PyRx, PyMoL, BIOVIA Discovery Studio tool (version 4.5), YASARA (dynamics simulator), and Cytoscape. Besides, as part of the online tools, the SwissDME and pKCSM were employed. The research study was proposed to implement molecular docking investigations utilizing compounds that were found to be effective against the viral primary protease (MPRO). MPRO protein interacted strongly with 10 amentoflavone derivatives. Every time, amentoflavone compounds outperformed the FDA-approved antiviral medicine that is currently underused in COVID-19 in terms of binding affinity (- 8.9, - 9.4, - 9.7, - 9.1, - 9.3, - 9.0, - 9.7, - 9.3, - 8.8, and - 9.0 kcal/mol, respectively). The best-selected derivatives of amentoflavone also possessed potential results in 100 ns molecular dynamic simulation (MDS) validation. It is conceivable that based on our in silico research these selected amentoflavone derivatives more precisely 4''''''-methylamentoflavone, ginkgetin, and sequoiaflavone have potential for serving as promising lead drugs against SARS-CoV-2 infection. In consequence, it is recommended that additional in vitro as well as in vivo research studies have to be conducted to support the conclusions of this current research study.

Amicoumacin-Based Prodrug Development Approach

Coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, is highly contagious and has a severe morbidity. Providing care to patients with COVID-19 requires the development of new types of antiviral drugs. The aim of this work is to develop a prodrug for the treatment of coronavirus disease using the antibiotic Amicoumacin A (Ami), the mechanism of action of which is based on translation inhibition. Enzymatic hydrolysis of an inactivated prodrug by the SARS-CoV-2 main protease can lead to the release of the active Ami molecule and, as a consequence, the suppression of protein biosynthesis in infected cells. To test the proposed hypothesis, a five-stage synthesis of an inactivated analogue of Amicoumacin A was carried out. Its in vitro testing with the SARS-CoV-2 recombinant protease MPro showed a low percentage of hydrolysis. Further optimization of the peptide fragment of the inactivated analog recognized by the SARS-CoV-2 MPro protease may lead to an increase in proteolysis and the release of Amicoumacin A.

Antiviral properties of trans-δ-viniferin derivatives against enveloped viruses.

Over the last century, the number of epidemics caused by RNA viruses has increased and the current SARS-CoV-2 pandemic has taught us about the compelling need for ready-to-use broad-spectrum antivirals. In this scenario, natural products stand out as a major historical source of drugs. We analyzed the antiviral effect of 4 stilbene dimers [1 (trans-δ-viniferin); 2 (11',13'-di-O-methyl-trans-δ-viniferin), 3 (11,13-di-O-methyl-trans-δ-viniferin); and 4 (11,13,11',13'-tetra-O-methyl-trans-δ-viniferin)] obtained from plant substrates using chemoenzymatic synthesis against a panel of enveloped viruses. We report that compounds 2 and 3 display a broad-spectrum antiviral activity, being able to effectively inhibit several strains of Influenza Viruses (IV), SARS-CoV-2 Delta and, to some extent, Herpes Simplex Virus 2 (HSV-2). Interestingly, the mechanism of action differs for each virus. We observed both a direct virucidal and a cell-mediated effect against IV, with a high barrier to antiviral resistance; a restricted cell-mediated mechanism of action against SARS-CoV-2 Delta and a direct virustatic activity against HSV-2. Of note, while the effect was lost against IV in tissue culture models of human airway epithelia, the antiviral activity was confirmed in this relevant model for SARS-CoV-2 Delta. Our results suggest that stilbene dimer derivatives are good candidate models for the treatment of enveloped virus infections.

Fractional order epidemiological model of SARS-CoV-2 dynamism involving Alzheimer's disease

In this paper, we study a Caputo-Fabrizio fractional order epidemiological model for the transmission dynamism of the severe acute respiratory syndrome coronavirus 2 pandemic and its relationship with Alzheimer's disease. Alzheimer's disease is incorporated into the model by evaluating its relevance to the quarantine strategy. We use functional techniques to demonstrate the proposed model stability under the Ulam-Hyres condition. The Adams-Bashforth method is used to determine the numerical solution for our proposed model. According to our numerical results, we notice that an increase in the quarantine parameter has minimal effect on the Alzheimer's disease compartment.Copyright © 2022 The Author(s)

Trajectory Tracking Analysis of Fractional-Order Nonlinear PID Controller for Single Link Robotic Manipulator System

Increasing demand for automation is being observed especially during the recent scenarios like the Covid-19 pandemic, wherein direct contact of the healthcare workers with the patients can be life-threatening. The use of robotic manipulators facilitates in minimizing such risky interactions and thereby providing a safe environment. In this research work, a single link robotic manipulator (SLRM) system is taken, which is a nonlinear multi–input–multi–output system. In order to address the limitations like heavy object movements, uncontrolled oscillations in positional movement, and improper link variations, an adaptive fractional-order nonlinear proportional, integral, and derivative (FONPID) controller has been suggested. This aids in the effective trajectory tracking of the performance of the SLRM system under step input response. Further, by tuning the controller gains using genetic algorithm optimization (GA) based on the minimum objective function (JIAE ) of the integral of absolute error (IAE) index, the suggested controller has been made more robust for trajectory tracking performance. Finally, the comparative analysis of the simulation results of proportional & integral (PI), proportional, integral, & derivative (PID), fractional-order proportional, integral, & derivative (FOPID), and the suggested FONPID controllers validated that the FONPID controller has performed better in terms of minimum JIAE and lower oscillation amplitude in trajectory tracking of positional movement of SLRM system. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Numerical Simulation for a Hybrid Variable-Order Multi-Vaccination COVID-19 Mathematical Model

In this paper, a hybrid variable-order mathematical model for multi-vaccination COVID-19 is analyzed. The hybrid variable-order derivative is defined as a linear combination of the variable-order integral of Riemann–Liouville and the variable-order Caputo derivative. A symmetry parameter σ is presented in order to be consistent with the physical model problem. The existence, uniqueness, boundedness and positivity of the proposed model are given. Moreover, the stability of the proposed model is discussed. The theta finite difference method with the discretization of the hybrid variable-order operator is developed for solving numerically the model problem. This method can be explicit or fully implicit with a large stability region depending on values of the factor Θ. The convergence and stability analysis of the proposed method are proved. Moreover, the fourth order generalized Runge–Kutta method is also used to study the proposed model. Comparative studies and numerical examples are presented. We found that the proposed model is also more general than the model in the previous study;the results obtained by the proposed method are more stable than previous research in this area.

Structure property relationship in two thiazole derivatives: Insights of crystal structure, Hirshfeld surface, DFT, QTAIM, NBO and molecular docking studies

Detailed structural and noncovalent interactions in two thiazole derivatives (N-(4-Bromophenyl)-2-(methylthio)thiazole-5-carboxamide and Ethyl-5-((4-bromophenyl)carbamoyl)thiazole-4-carboxylate) are investigated by single crystal X-ray diffraction study and computational approaches. The structure investigation revealed that various interactions like C-H…O, N-H…O, and N-H…N hydrogen bonds and Br…Br interactions are involved in constructing ring motifs to stabilize the crystal packing. Hirshfeld surface analysis and fingerprint plots were carried out to study the differences and similarities in the relative contribution of noncovalent interactions in both the molecules. The FMOs and other global reactive parameters are analyzed for thiazole derivatives. The strength and nature of weak interactions present in the molecule were characterized by RDG-based NCI and QTAIM analyses. Natural bond orbital (NBO) analysis unravels the importance of non-covalent and hyperconjugative interactions for the stability of the molecules in their solid state. Further, molecular docking of N-(4-Bromophenyl)-2-(methylthio)thiazole-5-carboxamide and Ethyl-5-((4-bromophenyl)carbamoyl)thiazole-4-carboxylate with SARS-Covid-19 have been carried out. © 2023 Taylor & Francis Group, LLC.

Fractional-type integral operators and their applications to trend estimation of COVID-19

In this paper, we construct a novel family of fractional-type integral operators of a function (Formula presented.) by replacing sample values (Formula presented.) with the fractional mean values of that function. We give some explicit formulas for higher order moments of the proposed operators and investigate some approximation properties. We also define the fractional variants of Mirakyan–Favard–Szász and Baskakov-type operators and calculate the higher order moments of these operators. We give an explicit formula for fractional derivatives of proposed operators with the help of the Caputo-type fractional derivative Furthermore, several graphical and numerical results are presented in detail to demonstrate the accuracy, applicability, and validity of the proposed operators. Finally, an illustrative real-world example associated with the recent trend of Covid-19 has been investigated to demonstrate the modeling capabilities of fractional-type integral operators. © 2023 John Wiley & Sons, Ltd.

Recent Advances in Anti-Tuberculosis Drug Discovery Based on Hydrazide-Hydrazone and Thiadiazole Derivatives Targeting InhA.

Tuberculosis is an extremely serious problem of global public health. Its incidence is worsened by the presence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. More serious forms of drug resistance have been observed in recent years. Therefore, the discovery and/or synthesis of new potent and less toxic anti-tubercular compounds is very critical, especially having in mind the consequences and the delays in treatment caused by the COVID-19 pandemic. Enoyl-acyl carrier protein reductase (InhA) is an important enzyme involved in the biosynthesis of mycolic acid, a major component of the M. tuberculosis cell wall. At the same time, it is a key enzyme in the development of drug resistance, making it an important target for the discovery of new antimycobacterial agents. Many different chemical scaffolds, including hydrazide hydrazones and thiadiazoles, have been evaluated for their InhA inhibitory activity. The aim of this review is to evaluate recently described hydrazide-hydrazone- and thiadiazole-containing derivatives that inhibit InhA activity, resulting in antimycobacterial effects. In addition, a brief review of the mechanisms of action of currently available anti-tuberculosis drugs is provided, including recently approved agents and molecules in clinical trials.