Evaluation of phytoconstituents of Tinospora cordifolia against K417N and N501Y mutant spike glycoprotein and main protease of SARS-CoV-2- an in silico study.

Coronavirus disease 2019 (COVID-19) caused appalling conditions over the globe, which is currently faced by the entire human population. One of the primary reasons behind the uncontrollable situation is the lack of specific therapeutics. In such conditions, drug repurposing of available drugs (viz. Chloroquine, Lopinavir, etc.) has been proposed, but various clinical and preclinical investigations indicated the toxicity and adverse side effects of these drugs. This study explores the inhibition potency of phytochemicals from Tinospora cordifolia (Giloy) against SARS CoV-2 drugable targets (spike glycoprotein and Mpro proteins) using molecular docking and MD simulation studies. ADMET, virtual screening, MD simulation, postsimulation analysis (RMSD, RMSF, Rg, SASA, PCA, FES) and MM-PBSA calculations were carried out to predict the inhibition efficacy of the phytochemicals against SARS CoV-2 targets. Tinospora compounds showed better binding affinity than the corresponding reference. Their binding affinity ranges from -9.63 to -5.68 kcal/mole with spike protein and -10.27 to -7.25 kcal/mole with main protease. Further 100 ns exhaustive simulation studies and MM-PBSA calculations supported favorable and stable binding of them. This work identifies Nine Tinospora compounds as potential inhibitors. Among those, 7-desacetoxy-6,7-dehydrogedunin was found to inhibit both spike (7NEG) and Mpro (7MGS and 6LU7) proteins, and Columbin was found to inhibit selected spike targets (7NEG and 7NX7). In all the analyses, these compounds performed well and confirms the stable binding. Hence the identified compounds, advocated as potential inhibitors can be taken for further in vitro and in vivo experimental validation to determine their anti-SARS-CoV-2 potential.Communicated by Ramaswamy H. Sarma.

The cross-talk between mucormycosis, steroids and diabetes mellitus amidst the global contagion of COVID-19.

Mucormycosis is an opportunistic fungal disease that targets individuals having an impaired immune system due to a wide array of risk factors including HIV-AIDS, immunosuppressive therapy, diabetes mellitus, etc. The current explosive outbreak of coronavirus disease 2019 (COVID-19) has become the latest threat to such patients who are already susceptible to secondary infections. Physiological outcomes of COVID-19 end up in a cascade of grave alterations to the immunological profile and irreparable harm to their respiratory passage, heart and kidneys. Corticosteroidal treatment facilitates faster recovery and alleviates the adverse pathological effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). But clinical reports lend this approach a darker perspective especially if these patients have pre-existing diabetes mellitus. The mucormycotic fungal genera belonging to the order Mucorales not only survive but thrive under the comorbidity of COVID-19 and diabetes, often staying undetected until they have inflicted irreversible damage. Steroidal usage has been noted to be a common thread in the sudden spurt in secondary fungal infections among COVID-19 cases. Once considered a rare occurrence, mucormycosis has now acquired a notoriously lethal status in mainstream medical hierarchy. We set out to investigate whether corticosteroidal therapy against COVID-19 emboldens the development of mucormycosis. We also assess the conditions brought forth by steroidal usage and uncontrolled progression of diabetes in COVID-19 cases and their effect on the susceptibility towards mucormycosis.

A review on synthesis of antiviral drugs, in silico studies and their toxicity

Viruses have been around us for a long period of time, they affect humans, animals and plant on cellular level by using host's body to dwell and reproduce. The spread of HIV was reported in 1981 and created a global threat to public health. In the areas of basic virology, immunology and pathogenesis of HIV/AIDS, the development of antiretroviral medicines and significant progress has been made in recent years. Majority of these antiviral compounds have the potential to be used as HIV drugs, however they are frequently accompanied with some side effects. With the emergence of the COVID-19, human race is facing a new public health crisis and repurposing of antiviral drugs to block the function of Mpro of the new corona virus has been started. This review covers the information related to the synthesis of various types of antiviral drugs and their toxicity. Some of these are used as repurposing drugs to cure patients suffering from other diseases, therefore, information for in Silico studies of antiviral drugs is incorporated. In brief, this review focused on different types of antiviral drugs, their synthesis, their repurposing role and the toxicity.

A review on 2D-ZnO nanostructure based biosensors: from materials to devices

During the COVID'19 outbreak, biosensing devices won increasing relevance, demonstrating their potential in the medical diagnostic field. Hence, the present review reports on the main advances in 2D-ZnO nanostructure-based biosensors. So far, bulk ZnO has shown potential for biosensing, optical, and power electronic applications, mainly based on its wide band gap. In the post graphene era, its 2-D allotropes like ZnO sheets and ZnO nanoribbons have outperformed the bulk ZnO structures for specific applications. ZnO demonstrates various stable and feasible morphologies: nanotubes, nanowires, nanorods, nanosheets, nanoparticles, and nanobelts. As a matrix layer in biosensing applications, ZnO strongly binds to biomolecules due to its high isoelectric point (IEP) and shows a strong sensitivity due to the high surface-to-volume ratio. Further, ZnO nanostructures used as a matrix layer play an important role in inhibiting specific biological interactions and hence improve the sensitivity of sensing devices. Further, bioselective layers are typically immobilized onto ZnO either by direct adsorption or by covalent binding. ZnO based biosensors are categorized into optical, piezoelectric, and electrochemical biosensors, among others, based on their biosensing mechanism. In particular, electrochemical sensors produce signals via an electrical pathway for detecting and monitoring the target molecules. Optical sensors produce signals based on luminescence or reflectance, among others. Piezoelectric biosensors produce signals by mass loading of the piezoelectric material. ZnO-based FET biosensors are also reported, showing sensing application by the change in the channel's conductance. Further, recent literature on the detection of COVID-19 using ZnO nanostructures is presented.

Role of Vitamin A Supplementation in Prevention and Control of Coronavirus Disease-19: A Narrative Review.

Coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 is a novel viral infectious disease, which broke out in the end of winter season 2019 in China and soon became a pandemic. Characteristically there was severe local and systemic immune-inflammatory response to the virus, damaging the respiratory system and other organ systems. The morbidity and mortality caused by the disease are producing tremendous impact on health. The understanding about pathogenesis and manifestations of the disease was obscure. To date, no classic treatment or preventive measure was available for COVID-19 other than symptomatic and supportive care or few drugs under trial. A possibility exists that maintaining vitamin A adequate levels can protect the affected respiratory mucosa, increase antimicrobial activity, produce better antibody response, and have antiinflammatory effects, thereby promoting repair and healing as well. It has been discussed in the review that by various mechanisms, immune regulation through vitamin A supplementation is beneficial to boost immunity in the current outbreak situation when the population is susceptible to the disease. There is a high possibility that vitamin A supplementation to cases as well as population at risk of COVID-19 has a key role in prevention and control. Hence, it is believed that along with other therapeutic and preventive measures, maintaining vitamin A sufficiency during and prior to the development of active disease may act as an adjuvant in population at risk and cases to prevent and control COVID-19.

Gate-all-around junctionless FET based label-free dielectric/charge modulation detection of SARS-CoV-2 virus† † Electronic supplementary information (ESI) available. See DOI: 10.1039/d1ra08587e

The recent corona outbreak has necessitated the development of a label-free, highly sensitive, fast, accurate, and cost-effective biosensor for the detection of SARS-CoV-2 virus. This study records the label-free electrical detection of the SARS-CoV-2 virus using the gate-all-around junctionless field effect transistor (GAA-JLFET) that detects the virus because of the electrical properties (dielectric constant and charge) of spike protein, envelope protein, and virus DNA, for a highly sensitive and real-time bio-sensor. GAA-JLFETs are suitable for this application because of their highest gate controllability, potential vertical stacking, current industry trend compatibility, inherent ease of fabrication, and higher sensitivity. The SARS-CoV-2 virus is first immobilized in the etched nano-cavity embedded beneath the gate electrode, which is then used to detect it. The SARS-CoV-2 virus detection has been calibrated based on the change in system electrical properties after virus immobilization. For effective virus detection, the work takes into account both the dielectric property of S protein and the charge of DNA at the same time. The sensitivity has been calculated using ΔVTH, ΔION, Δgm, and ΔSS. The simulation analysis also shows a simpler recovery mechanism in this case. The present work investigates the label-free electrical detection of the SARS-CoV-2 virus using GAA-JLFET that detects the spike protein, envelope protein, and virus DNA, for a highly sensitive and real-time bio-sensor.

Gate-all-around junctionless FET based label-free dielectric/charge modulation detection of SARS-CoV-2 virus.

The recent corona outbreak has necessitated the development of a label-free, highly sensitive, fast, accurate, and cost-effective biosensor for the detection of SARS-CoV-2 virus. This study records the label-free electrical detection of the SARS-CoV-2 virus using the gate-all-around junctionless field effect transistor (GAA-JLFET) that detects the virus because of the electrical properties (dielectric constant and charge) of spike protein, envelope protein, and virus DNA, for a highly sensitive and real-time bio-sensor. GAA-JLFETs are suitable for this application because of their highest gate controllability, potential vertical stacking, current industry trend compatibility, inherent ease of fabrication, and higher sensitivity. The SARS-CoV-2 virus is first immobilized in the etched nano-cavity embedded beneath the gate electrode, which is then used to detect it. The SARS-CoV-2 virus detection has been calibrated based on the change in system electrical properties after virus immobilization. For effective virus detection, the work takes into account both the dielectric property of S protein and the charge of DNA at the same time. The sensitivity has been calculated using ΔV TH, ΔI ON, Δg m, and ΔSS. The simulation analysis also shows a simpler recovery mechanism in this case.

Noscapine anticancer drug designed with ionic liquids to enhance solubility: DFT and ADME approach

Noscapine is an alkaloid based on the isoquinoline ring with many promising biological potential. Noscapine and its derivatives have shown potential as cough suppressant, anti-cancerous activity, ability to inhibit the main protease of SARS-CoV-2 and non-structural protease of chikungunya etc. Literature has reported the problem of solubility of noscapine due to high hydrophobic character, therefore, poorly soluble in water. In view of this, there is a need to find way to increase the solubility of noscapines. Ionic liquids (ILs) are organic salts and considered to have no or permissible toxicity. In the present work, authors report the designing of the ionic liquids (ILs) composed of noscapinium as cation with the different anions. Further, the designed noscapine based ionic liquids were studied using density functional theory (DFT) approach and time dependant density functional theory (TD-DFT). The thermo-chemical data of the designed ionic liquids revealed the stability and reactivity of ILs. Further, the IR and UV–visible spectra of the designed ILs were determined and analyzed. Then, the ADME behavior of designed ILs was calculated and studied using online servers. Based on the DFT calculations performed, (R)-5-((S)-4,5-dimethoxy-3-oxo-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6,6-dimethyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-6-ium trifluoromethanesulfonate (IL4) is found to be most soluble in the water and most stable amongst the designed ILs.

Two pronged approach for prevention and therapy of COVID-19 (Sars-CoV-2) by a multi-targeted herbal drug, a component of ayurvedic decoction.

INTRODUCTION: SARS-CoV-2 a new virus of the zoonotic coronavirus family causes the disease COVID-19, which has become a global pandemic. One of the ways for prevention of COVID-19 is by disabling its spike protein which results in inhibiting its binding with angiotensin-converting enzyme 2 (ACE-2). The other alternative is to inhibit its replication once inside the body. The aim of this study was to explore the literature to identify whether there were any Ayurvedic remedies which contained ingredients which demonstrated this dual effect. METHODS: In silico studies were carried out to find the structures of the targets i.e. spike protein of the virus and its main protease (Mpro). Databases were searched to identify the composition of Ayurvedic decoctions used for respiratory ailments. RESULTS: We have found that two components out of 26 active ingredients of Ayurvedic decoctions are strong binders for spike protein as well as corresponding Mpro (3CL protease) which plays an essential role in mediating viral replication and transcription, making it an attractive antiviral drug target. Out of 26 components of Ayurvedic herbal decoction used for influenza, one compound was found to be most active. It is a well-known antioxidant, antinflammatory and hepatoprotective molecule. CONCLUSION: The resultant compound could act as a repurposed drug or like other methoxyphenols, could be a good lead molecule for a potent drug for COVID-19.