A comprehensive profile of SARS-CoV-2 variants spreading during the COVID-19 pandemic: a genomic characterization study from Chhattisgarh State, India.

SARS-CoV-2 has expressively changed its sequences during the COVID-19 pandemic situation by encompassing persistent evolutionary mutational changes resulting in the emergence of many clades and lineages. Evolution of these SARS-CoV-2 variants have significantly imparted fitness advantage to the virus, enhanced its transmissibility and severity of the disease. These new variants are a potential threat to the vaccine efficacy as well. It is therefore pertinent to monitor the evolution of these variants and their epidemiological and clinical impact, in a geographic setting. This study has thus looked into the geographic distribution and genetic diversity of SARS-CoV-2 variants and the evolutionary circulation of different clades in Chhattisgarh (CG) state from March 2020 to July 2023. A total of 3018 sequences were retrieved from the GISAID database, in which 558 were submitted by us. The demographic data revealed male preponderance of 56.45% versus 43.54% females, with the overall mean age of 36.5 years. SARS-CoV-2 sequences represented many variants viz., Delta (55%), Omicron (22%) and others (15%) with a small proportion of recombinant (5%), Kappa (2%), and Alpha (1%). The viral clades G was found predominant for a year from initial days of pandemic in March, 2020 to January, 2021 which then subsequently evoluted to subclade GK (Delta B.1.617.2) and remained in circulation in CG till November, 2021. From December 2021, the GRA (Omicron B.1.1.529) variant had replaced GK to become the dominant strain and continues to predominate in present time. GRA clade is however continuously encompassing new recombinant strains, having various non-synonymous mutations especially in spike protein. The non-synonymous mutation P314L in ORF1b, S84L in ORF8 and D614G in spike protein were found as the pan mutation carried over from clade G to GRA. The continuous evolution in SARS-CoV2 warrants periodical geographic genomic surveillance monitoring to timely detect any new variants having the potential of causing future outbreak.

An Overview of SARS-CoV-2 Potential Targets, Inhibitors, and Computational Insights to Enrich the Promising Treatment Strategies.

The rapid spread of the SARS-CoV-2 virus has emphasized the urgent need for effective therapies to combat COVID-19. Investigating the potential targets, inhibitors, and in silico approaches pertinent to COVID-19 are of utmost need to develop novel therapeutic agents and reprofiling of existing FDA-approved drugs. This article reviews the viral enzymes and their counter receptors involved in the entry of SARS-CoV-2 into host cells, replication of genomic RNA, and controlling the host cell physiology. In addition, the study provides an overview of the computational techniques such as docking simulations, molecular dynamics, QSAR modeling, and homology modeling that have been used to find the FDA-approved drugs and other inhibitors against SARS-CoV-2. Furthermore, a comprehensive overview of virus-based and host-based druggable targets from a structural point of view, together with the reported therapeutic compounds against SARS-CoV-2 have also been presented. The current study offers future perspectives for research in the field of network pharmacology investigating the large unexplored molecular libraries. Overall, the present in-depth review aims to expedite the process of identifying and repurposing drugs for researchers involved in the field of COVID-19 drug discovery.

Genomic characterization unravelling the causative role of SARS-CoV-2 Delta variant of lineage B.1.617.2 in 2nd wave of COVID-19 pandemic in Chhattisgarh, India.

COVID-19 pandemic 2nd wave catastrophic effect in the state of Chhattisgarh, India, from where no exclusive genomic data yet published, has prompted us to undertake this study to unearth the causative variant. Whole-genome sequencing of SARS-CoV-2 isolated from COVID-19 infected nine vaccinated healthcare workers (HCW), thirty mild/moderate, seventeen severe, and twenty-seven deceased patients, was performed. The significant predominance of the SARS-CoV-2 variant of concern (VOC), Delta (lineage B.1.617.2) identified in sixty-four (77.1%) cases in contrast to B.1 and its sublineage in eleven (13.2%), variant under monitoring (VUM), Kappa (lineage B.1.617.1) in five (6.0%) and another VOC Alpha (lineage B.1.1.7) in three (3.6%) cases respectively (p < 0.05, χ2 = 162.49). 88.8% vaccine breakthrough, 60% mild/moderate, 94.4% severe and 81.5% dead patients were infected by Delta. Kappa presents exclusively in mild/moderate, Alpha in vaccine breakthrough, mild/moderate, and dead patient and B.1 and its sublineages in mild, severe, and dead patient categories. Delta variant spike mutation of T19R, G142D, E156G, L452R, and deletion (F157 and R158) helps in escaping antibody response, T478K and D614G enhance viral affinity with ACE2 receptor while P681R and D950N result in higher replication and transmissibility by cleaving S1/S2 at furin site. We conclude that Delta variant predominant role along with co-occurrence of Kappa, Alpha, and B.1 variant during COVID-19 2nd wave pandemic in Chhattisgarh may pose a potential threat of future outbreak through hybrid variant evolution. Thus, intensive genomic surveillance for monitoring variant evolution and a more efficacious vaccine against the Delta and Alpha variants are required.

Paradigms of actinorhizal symbiosis under the regime of global climatic changes: New insights and perspectives.

Nitrogen occurs as inert and inaccessible dinitrogen gaseous form (N2 ) in the atmosphere. Biological nitrogen fixation is a chief process that makes this dinitrogen (N2 ) accessible and bioavailable in the form of ammonium (NH4 + ) ions. The key organisms to fix nitrogen are certain prokaryotes, called diazotrophs either in the free-living form or establishing significant mutual relationships with a variety of plants. On such examples is ~95-100 MY old incomparable symbiosis between dicotyledonous trees and a unique actinobacterial diazotroph in diverse ecosystems. In this association, the root of the certain dicotyledonous tree (~25 genera and 225 species) belonging to three different taxonomic orders, Fagales, Cucurbitales, and Rosales (FaCuRo) known as actinorhizal trees can host a diazotroph, Frankia of order Frankiales. Frankia is gram-positive, branched, filamentous, sporulating, and free-living soil actinobacterium. It resides in the specialized, multilobed, and coralloid organs (lateral roots but without caps), the root nodules of actinorhizal tress. This review aims to provide systematic information on the distribution and the phylogenetic diversity of hosts from FaCuRo and their micro-endosymbionts (Frankia spp.), colonization mechanisms, and signaling pathways. We also aim to provide details on developmental and physiological imperatives for gene regulation and functional genomics of symbiosis, phenomenal restoration ecology, influences of contemporary global climatic changes, and anthropogenic impacts on plant-Frankia interactions for the functioning of ecosystems and the biosphere.

Mosaic Recombination Inflicted Various SARS-CoV-2 Lineages to Emerge into Novel Virus Variants: a Review Update.

Human Coronaviruses (hCoVs) belongs to the enormous and dissimilar family of positive-sense, non-segmented, single-stranded RNA viruses. The RNA viruses are prone to high rates of mutational recombination resulting in emergence of evolutionary variant to alter various features including transmissibility and severity. The evolutionary changes affect the immune escape and reduce effectiveness of diagnostic and therapeutic measures by becoming undetectable by the currently available diagnostics and refractory to therapeutics and vaccines. Whole genome sequencing studies from various countries have adequately reported mosaic recombination between different lineage strain of SARS-CoV-2 whereby RNA dependent RNA polymerase (RdRp) gene reconnects with a homologous RNA strand at diverse position. This all lead to evolutionary emergence of new variant/ lineage as evident with the emergence of XBB in India at the time of writing this review. The continuous periodical genomic surveillance is utmost required for understanding the various lineages involved in recombination to emerge into hybrid variant. This may further help in assessing virus transmission dynamics, virulence and severity factor to help health authorities take appropriate timely action for prevention and control of any future COVID-19 outbreak.

A highly efficient bilayer graphene/ZnO/silicon nanowire based heterojunction photodetector with broadband spectral response.

This paper presents three self-powered photodetectors namely, p+-bilayer graphene (BLG)/n+-ZnO nanowires (NWs), p+-BLG/n+-Si NWs/p--Si and p+-BLG/n+-ZnO NWs/p--Si. The Silvaco Atlas TCAD software is utilized to characterize the optoelectronic properties of all the devices and is validated by analytical modeling. The proposed dual-junction photodetectors cover broadband spectral response varying from ultraviolet to near-infrared wavelengths. The dual-heterojunction broadband photodetector exhibits photocurrent switching with the rise and fall time of 1.48 and 1.27 ns, respectively. At -0.5 V bias, the highest external quantum efficiency, photocurrent responsivity, specific detectivity, and the lowest noise equivalent power of 71%, 0.28 A W-1, 4.2 × 1012 cmHz1/2 W-1, and 2.59 × 10-17 W, respectively, are found for the dual-heterojunction device with a wavelength of 480 nm at 300 K. The proposed nanowires based photodetectors offer great potential to be utilized as next-generation optoelectronic devices.

Genetic diversity and association mapping of bacterial blight and other horticulturally important traits with microsatellite markers in pomegranate from India.

This genetic diversity study aimed to estimate the population structure and explore the use of association mapping strategies to identify linked markers for bacterial resistance, growth and fruit quality in pomegranate collections from India. In total, 88 accessions including 37 cultivated types were investigated. A total of 112 alleles were amplified by use of 44 publicly available microsatellites for estimating molecular genetic diversity and population structure. Neighbor-joining analysis, model-based population structure and principal component analysis corroborated the genetic relationships among wild-type and cultivated pomegranate collections from India. Our study placed all 88 germplasm into four clusters. We identified a cultivated clade of pomegranates in close proximity to Daru types of wild-type pomegranates that grow naturally near the foothills of the Himalayas. Admixture analysis sorted various lineages of cultivated pomegranates to their respective ancestral forms. We identified four linked markers for fruit weight, titratable acidity and bacterial blight severity. PGCT001 was found associated with both fruit weight and bacterial blight, and the association with fruit weight during both seasons analyzed was significant after Bonferroni correction. This research demonstrates effectiveness of microsatellites to resolve population structure among the wild and cultivar collection of pomegranates and future use for association mapping studies.

Quantitation of VEGFR2 (vascular endothelial growth factor receptor) inhibitors--review of assay methodologies and perspectives.

The introduction of small-molecule tyrosine kinase VEGFR2 (vascular endothelial growth factor receptor) inhibitors has added another dimension in the treatment of several oncology indications as they offer a unique mechanism. The VEGFR2 inhibitors have demonstrated superior benefits in treating certain types of cancer, such as renal cell carcinoma and hepatocellular carcinoma, as a monotherapy option. Many of the approved VEGFR2 inhibitors have also shown promise when used in combination with other anticancer agents. There are numerous bioanalytical methods published for the analysis of VEGFR2 inhibitors in preclinical and clinical samples. This review covers VEGFR2 inhibitors such as sunitinib, sorafenib, pazopanib and JI-101. In addition to providing a comprehensive review of the available methods for the above-mentioned VRGFR2 inhibitors, it also provides information on assays that can simultaneously measure multiple tyrosine kinase inhibitors, including VEGFR2 molecules. Based on the review, the published methodologies using LC/MS-MS or HPLC-UV are adequate for the quantification of the VEGFR2 inhibitors and can easily be established in a modern day bioanalytical laboratory. The availability of a plethora of assays for multiple tyrosine kinase inhibitors makes it easy to analyze a panel of compounds to support either therapeutic drug monitoring and/or clinical pharmacokinetics.

A validated LC-MS/MS assay for simultaneous quantification of methotrexate and tofacitinib in rat plasma: application to a pharmacokinetic study.

A highly sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for simultaneous quantification of methotrexate (MTX) and tofacitinib (TFB) in rat plasma (50 µL) using phenacetin as an internal standard (IS), as per the US Food and Drug Administration guidelines. After a solid-phase extraction procedure, the separation of the analytes and IS was performed on a Chromolith RP18e column using an isocratic mobile phase of 5 m m ammonium acetate (pH 5.0) and acetonitrile at a ratio of 25:75 (v/v) using flow-gradient with a total run time of 3.5 min. The detection was performed in multiple reaction monitoring mode, using the transitions of m/z 455.2 → 308.3, m/z 313.2 → 149.2 and m/z 180.3 → 110.2 for MTX, TFB and IS, respectively. The calibration curves were linear over the range of 0.49-91.0 and 0.40-74.4 ng/mL for MTX and TFB, respectively. The intra- and interday accuracy and precision values for MTX and TFB were <15% at low quality control (QC), medium QC and high QC and <20% at lower limit of quantification. The validated assay was applied to derive the pharmacokinetic parameters for MTX and TFB post-dosing of MTX and TFB orally and intravenously to rats.

Development and validation of a RP-HPLC method for the quantitation of tofacitinib in rat plasma and its application to a pharmacokinetic study.

A novel, simple, specific, sensitive and reproducible high-performance liquid chromatography (HPLC) assay method has been developed and validated for the estimation of tofacitinib in rat plasma. The bioanalytical procedure involves extraction of tofacitinib and itraconazole (internal standard, IS) from rat plasma with a simple liquid-liquid extraction process. The chromatographic analysis was performed on a Waters Alliance system using a gradient mobile phase conditions at a flow rate of 1.0 mL/min and C18 column maintained at 40 ± 1 °C. The eluate was monitored using an UV detector set at 287 nm. Tofacitinib and IS eluted at 6.5 and 8.3 min, respectively and the total run time was 10 min. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curve was linear over a concentration range of 182-5035 ng/mL (r(2) = 0.995). The intra- and inter-day precisions were in the range of 1.41-11.2 and 3.66-8.81%, respectively, in rat plasma. The validated HPLC method was successfully applied to a pharmacokinetic study in rats.

Chemoradiation in elderly patients with head and neck cancers: a single institution experience.

AIMS: To evaluate the efficacy and toxicity of concurrent chemoradiation in patients with head and neck cancers aged 65 and older. MATERIALS AND METHODS: Thirty-two elderly patients were treated with radical chemoradiation. Twenty-six (81.3%) out of thirty-two patients had stage III-IV disease. Twenty-nine (90.6%) patients received concurrent weekly cisplatin or carboplatin, 3 (9.4%) patients received concurrent cetuximab or nimotuzumab. Total dose of radiotherapy ranged from 66Gy to 70Gy. RESULTS: Twenty-nine patients (90.6%) completed at least 5cycles of concurrent chemotherapy. Twenty-four (77.6%) patients achieved complete response. Fourteen (45.2%) patients experienced grade 3 mucositis. None of our patients developed grade 3 or above hematological toxicity. Loco-regional control and overall survival at 2year were 71.6% and 88.9%, respectively. CONCLUSIONS: Chemoradiation in elderly patients with high precision radiotherapy is a feasible option.

Review of the validated HPLC and LC-MS/MS methods for determination of drugs used in clinical practice for Alzheimer's disease.

Alzheimer's disease (AD) is a neurological disorder and is the most frequent type of dementia among elderly people. Donepezil, rivastigmine, galantamine, tacrine and memantine are the US Food and Drug Administration approved oral drugs used in the treatment of AD. Quantitation of these drugs in various biological matrices and monitoring them in long-term treatment is essential to titer the dose of these drugs and ensure patient compliance. This review provides a comprehensive account of various HPLC and LC-MS/MS assays, which have been successfully employed to measure the drug levels in various biological matrices arising from preclinical and clinical studies. In addition, this review collates various considerations such as internal standard selection, extraction schemes, matrix effect, selectivity evaluation and optimization of mass spectrometric conditions to enable the development of sound bioanalytical methods for quantitation of Alzheimer's drugs. Overall LC-MS/MS methods have proven to be the choice of bioanalytical method for the quantification of Alzheimer's drugs in both preclinical and clinical studies. In conclusion, important features of LC-MS/MS methodology for Alzheimer's drugs include shortened analysis time, increased throughput, selectivity and lower cost of analysis.

Genomic characterization of Influenza A (H1N1)pdm09 and SARS-CoV-2 from Influenza Like Illness (ILI) and Severe Acute Respiratory Illness (SARI) cases reported between July-December, 2022.

Influenza Like Illness (ILI) and Severe Acute Respiratory Infection (SARI) cases are more prone to Influenza and SARS-CoV-2 infection. Accordingly, we genetically characterized Influenza and SARS-CoV-2 in 633 ILI and SARI cases by rRT-PCR and WGS. ILI and SARI cases showed H1N1pdm09 prevalence of 20.9% and 23.2% respectively. 135 (21.3%) H1N1pdm09 and 23 (3.6%) H3N2 and 5 coinfection (0.78%) of H1N1pdm09 and SARS-CoV-2 were detected. Phylogenetic analysis revealed H1N1pdm09 resemblance to clade 6B.1A.5a.2 and their genetic relatedness to InfA/Perth/34/2020, InfA/Victoria/88/2020 and InfA/Victoria/2570/2019. Pan 24 HA and 26 NA nonsynonymous mutations and novel HA (G6D, Y7F, Y78H, P212L, G339R, T508K and S523T) and NA (S229A) mutations were observed. S74R, N129D, N156K, S162N, K163Q and S164T alter HA Cb and Sa antibody recognizing site. Similarly, M19T, V13T substitution and multiple mutations in transmembrane and NA head domain drive antigenic drift. SARS-CoV-2 strains genetically characterized to Omicron BA.2.75 lineage containing thirty nonsynonymous spike mutations exhibited enhanced virulence and transmission rates. Coinfection although detected very minimal, the mutational changes in H1N1pdm09 and SARS-CoV-2 virus infected individuals could alter antibody receptor binding sites, allowing the viruses to escape immune response resulting in better adaptability and transmission. Thus continuous genomic surveillance is required to tackle any future outbreak.

Polyethylene terephthalate waste derived nanomaterials (WDNMs) and its utilization in electrochemical devices.

Plastics are a vital component of our daily lives in the contemporary globalization period; they are present in all facets of modern life. Because the bulk of synthetic plastics utilized in the market are non-biodegradable by nature, the issues associated with their contamination are unavoidable in an era dominated by polymers. Polyethylene terephthalate (PET), which is extensively used in industries such as automotive, packaging, textile, food, and beverages production represents a major share of these non-biodegradable polymer productions. Given its extensive application across various sectors, PET usage results in a considerable amount of post-consumer waste, majority of which require disposal after a certain period. However, the recycling of polymeric waste materials has emerged as a prominent topic in research, driven by growing environmental consciousness. Numerous studies indicate that products derived from polymeric waste can be converted into a new polymeric resource in diverse sectors, including organic coatings and regenerative medicine. This review aims to consolidate significant scientific literatures on the recycling PET waste for electrochemical device applications. It also highlights the current challenges in scaling up these processes for industrial application.

Green route to fabrication of Semal-ZnO nanoparticles for efficient solar-driven catalysis of noxious dyes in diverse aquatic environments.

This work successfully demonstrates a sustainable and environmentally friendly approach for synthesizing Semal-ZnO nanoparticles (NPs) using the aqueous leaf extract of Bombax ceiba L. These NPs exhibit an absorption peak at approximately 390 nm in the UV-visible spectrum and an energy gap (Eg) of 3.11 eV. Detailed analyses of the morphology and particle size using various spectroscopic and microscopic techniques, XRD, FE-SEM with EDS, and HR-TEM reveal crystallographic peaks attributable to the hexagonal phase, with an average crystal size of 17 nm. The Semal-ZnO NPs also exhibit a notable photocatalytic efficiency for degrading methylene blue (MB) and methyl orange (MO) under sunlight in different water samples collected from diverse natural sources, indicating that they are promising photocatalysts for environmental remediation. The photocatalytic efficiency of the biofabricated Semal-ZnO NPs is impressive, exhibiting a photodegradation rate of up to 99% for MB and 79% for MO in different water samples under exposure to sunlight. The novel phytofabricated Semal-ZnO NPs are thus a beacon of hope for the environment, with their desirable photocatalytic efficiency, pseudo-first-order kinetics, and ability to break down noxious dye pollutants in various aquatic environments.

A concise review of HPLC, LC-MS and LC-MS/MS methods for determination of azithromycin in various biological matrices.

Azithromycin is one of the best selling antibiotics in the world. It belongs to the new macrolide family of azalides. It is derived from erythromycin and it differs from erythromycin in having a 15-membered ring and a methyl substituted nitrogen inserted at the 9a position in the aglycone ring. This structural modification confers favourable microbiological and pharmacokinetic characteristics on azithromycin and greater acid stability compared with erythromycin. It is mainly used to treat respiratory infections, sexually transmitted diseases, cutaneous and soft-tissue infections, etc. This review provides a comprehensive overview of various HPLC, LC-MS and LC-MS/MS methods for quantitation of azithromycin in different biological matrices. In addition, it provides general information on extraction steps, internal standard selection, conditions for chromatographic separation, brief validation data and applicable conclusions for reported methods in a defined pattern.

LC-MS/MS-ESI method for simultaneous quantitation of metformin and repaglinidie in rat plasma and its application to pharmacokinetic study in rats.

A highly sensitive and specific LC-MS/MS-ESI method has been developed for simultaneous quantification of metformin (MFN) and repaglinide (RGN) in rat plasma (50 µL) using phenacetin as an internal standard (IS). Simple protein precipitation was used to extract MFN and RGN from rat plasma. The chromatographic resolution of MFN, RGN and IS was achieved with a mobile phase consisting of 0.2% formic acid in water-acetonitrile (1:1, v/v) with a time program flow gradient on a Chromolith RP-18e column. The total chromatographic run time was 3.5 min and the elution of MFN, RGN and IS occurred at 1.64, 2.21 and 2.15 min, respectively. A linear response function was established for the range of concentrations 0.855-394 and 0.021-21.7 ng/mL for MFN and RGN, respectively. The intra- and inter-day precision values for MFN and RGN met the acceptance as per FDA guidelines. MFN and RGN were stable in battery of stability studies viz., bench-top, auto-sampler and freeze-thaw cycles. The developed assay was applied to a pharmacokinetic study in rats.

Frame-based radiosurgery: Is it relevant in the era of IGRT?

PURPOSE: To assess the setup errors and intrafraction motion in patients treated with frame-based and frameless stereotactic radiosurgery (SRS). MATERIALS AND METHODS: Ten patients treated with frame-based and six patients treated with frameless radiosurgery were prospectively enrolled in the study. Leksell frame was used for frame-based and a customized uniframe orfit cast for frameless techniques. Cone beam computed tomography (CBCT) scans were taken immediately before and after each treatment to evaluate the positional accuracy and corrections applied with the use of hexapod couch for both groups. RESULTS: The mean translational shifts with frame-based SRS were 1.00 ± 0.30 mm in the lateral direction (X), 0.20 ± 1.20 mm in craniocaudal direction (Y) and -0.10 ± 0.31 mm in the anteroposterior direction (Z). The rotational shifts for frame-based treatments were as follows: roll 0.32 ± 0.70, pitch 0.44 ± 0.66 and yaw 0.20 ± 0.4. For frameless SRS, translational shifts were -0.40 ± 0.90, 1.10 ± 1.10, and 0.50 ± 1.30 mm in X, Y, and Z directions, respectively, and rotational shifts were -0.11 ± 0.78, 0.20 ± 0.44, and 0.29 ± 0.35 in roll, pitch, and yaw, respectively. Intrafraction shifts with frame-based SRS were: X = 0.60 ± 1.80 mm, Y = 0.20 ± 0.60 mm, and Z = 0.00 ± 0.05 mm; and rotational shifts were: roll 0.01 ± 0.27, pitch 0.06 ± 0.15, and yaw 0.01 ± 0.09. For frameless SRS, these were: X = 0.11 ± 0.20 mm, Y = 0.20 ± 0.40 mm, and Z = 0.20 ± 0.20 mm and rotational shifts were: roll 0.09 ± 0.23, pitch 0.00 ± 0.12, and yaw 0.00 ± 0.09. CONCLUSIONS: In our experience, set up accuracy of frameless SRS is as good as frame-based SRS. With availability of verification methods such as CBCT and hexapod couch, an accurate and precise treatment delivery is feasible with frameless techniques.

Time-dependent plastic behavior of bacteria leading to rupture.

A study of the mechanical response of bacteria is essential in designing an antibacterial surface for implants and food packaging applications. This research evaluated the mechanical response of Escherichia coli under different loading conditions. Indentation and prolonged creep tests were performed to understand their viscoelastic-plastic response. The results indicate that varying loading rates from 1 µm/s to 5 µm/s show an increase in modulus of 182% and 90%, calculated in the loading and unloading cycles, respectively, and a decrease in adhesion force by 42%. However, on varying loads from 5 nN to 25 nN, nominal change is observed in both modulus and adhesion force. The rupture curve at 100 nN load shows elastic and a small plastic deformation accompanied by a sharp peak indicating the cell wall rupture. The rupture force at the peak was found to be 34.38 ± 5.15 nN, irrespective of the loading rate, making it a failure criterion for bacteria rupture. The creep response of bacteria increases (for 6 s) and then remains constant (for 15 s) with time, indicating that a standard linear solid (SLS) model applies to this behavior. This work attempts to evaluate the mechanical properties of E. coli bacteria focusing on its rupture by contact killing mechanism.

Identification of a promising inhibitor from Illicium verum (star anise) against the main protease of SARS-CoV-2: insights from the computational study.

SARS-CoV-2, the causing agent of coronavirus disease (COVID-19), first broke out in Wuhan and rapidly spread worldwide, resulting in a global health emergency. The lack of specific drugs against the coronavirus has made its spread challenging to control. The main protease (Mpro) is a key enzyme of SARS-CoV-2 used as a key target in drug discovery against the coronavirus. Medicines derived from plant phytoconstituents have been widely exploited to treat various diseases. The present study has evaluated the potential of Illicium verum (star anise) phytoconstituents against Mpro by implementing a computational approach. We performed molecular docking and molecular dynamics simulation study with a set of 60 compounds to identify their potential to inhibit the main protease (Mpro) of SARS-CoV-2. DFT study and post dynamics free energy calculations were also performed to strengthen the findings. The identified four compounds by docking study exhibited the highest potential compared to other selected phytoconstituents. Further, density functional theory (DFT) calculation, molecular dynamics simulation and post dynamics MM-GBSA energy calculation predicted Verimol-G as a potential compound, which formed stable interactions through the catalytic dyad residues. The HOMO orbital energy (-0.250038) from DFT and the post dynamics binding free energy calculation (-73.33 Kcal/mol) correlate, suggesting Verimol-G is the best inhibitor compared to the other phytoconstituents. This compound also complies with the ADME properties of drug likeliness. Thus, based on a computational study, we suggest that Verimol G may be developed as a potential inhibitor against the main protease to combat COVID-19.Communicated by Ramaswamy H. Sarma.