Therapeutic potential of natural products and antibiotics against bovine mastitis pathogen of cows and buffaloes.

The present study aims to evaluate the prevalence and antimicrobial sensitivity of Staphylococcus aureus associated with bovine mastitis to selected antibiotics and plant extracts. In the current study, 140 milk samples were collected from cows and buffaloes. Among the 140 samples, 93 samples were positive for sub-clinical mastitis based on the California Mastitis Test (CMT). Out of the total positive samples, 45 were confirmed for S. aureus on a Mannitol salt agar media. The antimicrobial susceptibility test revealed that 44.82% of the isolates were resistant to cefoxitin (oxacillin) confirming methicillin-resistant S. aureus (MRSA) with a higher percentage (51.61%) in the buffalo than in the cow samples. Furthermore, the PCR assay confirmed the presence of the mecA gene in all the MRSA isolates. Among the seven tested antibiotics, sulfamethoxazole + trimethoprim showed high efficacy (71.1%) against methicillin-susceptible S. aureus isolates (MSSA). Oxytetracycline and sulfamethoxazole + trimethoprim showed 20% efficacy against MRSA followed by enrofloxacin (10%). On the other hand, the tested samples from Pistacia chinensis revealed that the ethyl acetate extract of bark showed a maximum zone of inhibition of 21.3 mm against MSSA and MRSA isolates at 3 000 µg/disc. Moreover, the methanol extract of Cotoneaster microphyllus formed a 12.3 mm and 9.1 mm zone of inhibition against the MSSA and MRSA isolates, respectively.

Comparing two approaches of miR-34a target identification, biotinylated-miRNA pulldown vs miRNA overexpression.

microRNAs (miRNAs) are critical regulators of gene expression. For elucidating functional roles of miRNAs, it is critical to identify their direct targets. There are debates about whether pulldown of biotinylated miRNA mimics can be used to identify miRNA targets or not. Here we show that biotin-labelled miR-34a can be loaded to AGO2, and AGO2 immunoprecipitation can pulldown biotinylated miR-34a (Bio-miR pulldown). RNA-sequencing (RNA-seq) of the Bio-miR pulldown RNAs efficiently identified miR-34a mRNA targets, which could be verified with luciferase assays. In contrast to the approach of Bio-miR pulldown, RNA-seq of miR-34a overexpression samples had limited value in identifying direct targets of miR-34a. It seems that pulldown of 3'-Biotin-tagged miRNA can identify bona fide microRNA targets at least for miR-34a.

The isolation of an RNA aptamer targeting to p53 protein with single amino acid mutation.

p53, known as a tumor suppressor, is a DNA binding protein that regulates cell cycle, activates DNA repair proteins, and triggers apoptosis in multicellular animals. More than 50% of human cancers contain a mutation or deletion of the p53 gene, and p53R175 is one of the hot spots of p53 mutation. Nucleic acid aptamers are short single-stranded oligonucleotides that are able to bind various targets, and they are typically isolated from an experimental procedure called systematic evolution of ligand exponential enrichment (SELEX). Using a previously unidentified strategy of contrast screening with SELEX, we have isolated an RNA aptamer targeting p53R175H. This RNA aptamer (p53R175H-APT) has a significantly stronger affinity to p53R175H than to the wild-type p53 in both in vitro and in vivo assays. p53R175H-APT decreased the growth rate, weakened the migration capability, and triggered apoptosis in human lung cancer cells harboring p53R175H. Further analysis actually indicated that p53R175H-APT might partially rescue or correct the p53R175H to function more like the wild-type p53. In situ injections of p53R175H-APT to the tumor xenografts confirmed the effects of this RNA aptamer on p53R175H mutation in mice.

Induction of miR-3648 Upon ER Stress and Its Regulatory Role in Cell Proliferation.

MicroRNAs (miRNAs) play important roles under multiple cellular conditions including endoplasmic reticulum (ER) stress. We found that miR-3648, a human specific microRNA, was induced under ER stress. Moreover, Adenomatous polyposis coli 2 (APC2), a tumor suppressor and a negative regulator of Wnt signaling, was found to be the direct target of miR-3648. Levels of APC2 were downregulated when cells were under ER stress or after overexpressing miR-3648. Inhibition of miR-3648 by antagomir increased APC2 levels and decreased cell proliferation. Conversely, when miR-3648 was overexpressed, APC2 levels were decreased and the cell growth increased. Our data demonstrated that ER stress mediated induction of miR-3648 in human cells, which then downregulated APC2 to increase cell proliferation.

Synthesis, characterization and biological evaluation of some 5-methylpyrazine carbohydrazide based hydrazones.

Pyrazine carbohydrazide based hydrazones were synthesized starting from 5-methylpyrazine-2-carboxylic acid. The acid was first converted to its methyl ester, which on further treatment with hydrazine hydrate transformed to carbohydrazide. The carbohydrazide was treated with differently substituted aromatic carbonyl compounds giving hydrazones. Characterization of the synthesized compounds was carried out using modern spectroscopic techniques and unambiguously confirmed through X-ray crystallographic studies of compound 3d. The purity of the compounds was verified using elemental analysis. The target molecules were evaluated for urease inhibition, antioxidant and antimicrobial activity.

One pot light assisted green synthesis, storage and antimicrobial activity of dextran stabilized silver nanoparticles.

BACKGROUND: Green synthesis of nanomaterials finds the edge over chemical methods due to its environmental compatibility. Herein, we report green synthesis of silver nanoparticles (Ag NPs) mediated with dextran. Dextran was used as a stabilizer and capping agent to synthesize Ag NPs using silver nitrate (AgNO3) under diffused sunlight conditions. RESULTS: UV-vis spectra of as synthesized Ag nanoparticles showed characteristic surface plasmon band in the range from ~405-452 nm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) studies showed spherical Ag NPs in the size regime of ~50-70 nm. Face centered cubic lattice of Ag NPs was confirmed by powder X-ray diffraction (PXRD). FT-IR spectroscopy confirmed that dextran not only acts as reducing agent but also functionalizes the surfaces of Ag NPs to make very stable dispersions. Moreover, on drying, the solution of dextran stabilized Ag NPs resulted in the formation of thin films which were found stable over months with no change in the plasmon band of pristine Ag NPs. The antimicrobial assay of the as synthesized Ag NPs showed remarkable activity. CONCLUSION: Being significantly active against microbes, the Ag NPs can be explored for antimicrobial medical devices.

Incidental Finding of Post-Transplant Erythrocytosis After Renal Transplantation in a Patient With Chronic Kidney Disease: A Case Report.

Renal transplant aims to provide a healthy substitute for the chronically damaged kidney while also correcting the anemia of chronic disease by producing erythropoietin for effective erythropoiesis. However, in a small number of renal transplant patients, the hematocrit continues to rise even after correction of the anemia, ultimately leading to abnormally increased hemoglobin and hematocrit. This condition is termed "post-transplant erythrocytosis" (PTE). We present a case of a 50-year-old male who was diabetic, positive for hepatitis B surface antigen, and negative for polymerase chain reaction. He presented with symptoms of acute hepatitis. During the work-up, PTE was diagnosed. Our case sheds light on a common complication of renal transplant known as PTE, its possible complications in the patient, and the necessary interventions to prevent untoward outcomes. PTE, although a less common complication of renal transplant, can become serious and potentially fatal due to its sequelae of thromboembolism. The complications can range from simple thrombophlebitis and thrombosis of digital and brachial arteries to more severe events such as pulmonary embolism or stroke and cardiovascular events. Regular post-transplant follow-ups with frequent bloodwork will aid in the early diagnosis of PTE, allowing for timely intervention with appropriate treatment options such as venesection or angiotensin receptor blockers (ARBs)/angiotensin-converting enzyme (ACE) inhibitors.

An operator splitting scheme for numerical simulation of spinodal decomposition and microstructure evolution of binary alloys.

This article compares the operator splitting scheme to linearly stabilized splitting and semi-implicit Euler's schemes for the numerical solution of the Cahn-Hilliard equation. For the purpose of validation, the spinodal decomposition phenomena have been simulated. The efficacy of the three schemes has been demonstrated through numerical experiments. The computed results show that the schemes are conditionally stable. It has been observed that the operator splitting scheme is computationally more efficient.

Comparative mutational analysis of the Zika virus genome from different geographical locations and its effect on the efficacy of Zika virus-specific neutralizing antibodies.

The Zika virus (ZIKV), which originated in Africa, has become a significant global health threat. It is an RNA virus that continues to mutate and accumulate multiple mutations in its genome. These genetic changes can impact the virus's ability to infect, cause disease, spread, evade the immune system, and drug resistance. In this study genome-wide analysis of 175 ZIKV isolates deposited at the National Center for Biotechnology Information (NCBI), was carried out. The comprehensive mutational analysis of these isolates was carried out by DNASTAR and Clustal W software, which revealed 257 different substitutions at the proteome level in different proteins when compared to the reference sequence (KX369547.1). The substitutions were capsid (17/257), preM (17/257), envelope (44/257), NS1 (34/257), NS2A (30/257), NS2B (11/257), NS3 (37/257), NS4A (6/257), 2K (1/257), NS4B (15/257), and NS5 (56/257). Based on the coexisting mutational analysis, the MN025403.1 isolate from Guinea was identified as having 111 substitutions in proteins and 6 deletions. The effect of coexisting/reoccurring mutations on the structural stability of each protein was also determined by I-mutant and MUpro online servers. Furthermore, molecular docking and simulation results showed that the coexisting mutations (I317V and E393D) in Domain III (DIII) of the envelope protein enhanced the bonding network with ZIKV-specific neutralizing antibodies. This study, therefore, highlighted the rapid accumulation of different substitutions in various ZIKV proteins circulating in different geographical regions of the world. Surveillance of such mutations in the respective proteins will be helpful in the development of effective ZIKV vaccines and neutralizing antibody engineering.

Efficacy and Safety of Potassium-Competitive Acid Blockers Versus Proton Pump Inhibitors as Helicobacter pylori Eradication Therapy: A Meta-Analysis of Randomized Clinical Trials.

Helicobacter pylori is a gram-negative bacterium that chronically infects the gastric epithelium. Potassium-competitive acid blockers (P-CABs) are a promising alternative, being more potent than standard proton pump inhibitors (PPIs). The meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria were randomized controlled trials (RCTs) comparing P-CAB and PPI-based therapy, confirmed H. pylori infection, and measured eradication rates after at least four weeks. Subgroup analyses were conducted based on therapy type and trial location. Quality assessment used the Cochrane risk-of-bias tool, RoB 2.0, and statistical analysis was performed using ReviewManager (RevMan) 5.4 (2020; The Cochrane Collaboration, London, United Kingdom). A p-value of <0.05 is considered statistically significant. In the intention-to-treat (ITT) analysis, P-CABs demonstrated superior overall efficacy, consistently observed in the first-line treatment subgroup. However, no significant difference was found in the subgroup receiving salvage therapy. Another ITT subgroup analyzed the impact of geographical location, favoring P-CABs in the overall study population and the Japanese subgroup. However, no statistically significant differences were found in the subgroups of other countries. In the PPA, P-CABs showed superior efficacy overall, consistently seen in the first-line treatment subgroup. However, no significant difference was found in the subgroup receiving salvage eradication therapy. Another PPA subgroup analysis considered the geographical impact on eradication rates, revealing P-CABs as superior to PPIs in the overall study population and the Japanese subgroup, but not in other countries. No significant adverse event outcomes were observed. P-CAB-based triple therapy is more effective than PPI-based triple therapy as the primary treatment for H. pylori eradication, particularly in Japanese patients. Nevertheless, regarding salvage therapy, both treatments show comparable efficacy. Additionally, the tolerability of P-CAB-based and PPI-based triple therapy is similar, with a similar occurrence of adverse events.

A performance comparison of machine learning models for stock market prediction with novel investment strategy.

Stock market forecasting is one of the most challenging problems in today's financial markets. According to the efficient market hypothesis, it is almost impossible to predict the stock market with 100% accuracy. However, Machine Learning (ML) methods can improve stock market predictions to some extent. In this paper, a novel strategy is proposed to improve the prediction efficiency of ML models for financial markets. Nine ML models are used to predict the direction of the stock market. First, these models are trained and validated using the traditional methodology on a historic data captured over a 1-day time frame. Then, the models are trained using the proposed methodology. Following the traditional methodology, Logistic Regression achieved the highest accuracy of 85.51% followed by XG Boost and Random Forest. With the proposed strategy, the Random Forest model achieved the highest accuracy of 91.27% followed by XG Boost, ADA Boost and ANN. In the later part of the paper, it is shown that only classification report is not sufficient to validate the performance of ML model for stock market prediction. A simulation model of the financial market is used in order to evaluate the risk, maximum draw down and returns associate with each ML model. The overall results demonstrated that the proposed strategy not only improves the stock market returns but also reduces the risks associated with each ML model.

Investigation of conduction mechanism and UV light response of vertically grown ZnO nanorods on an interdigitated electrode substrate.

Vertically aligned zinc oxide nanorod (ZnO-NR) growth was achieved through a wet chemical route over a comb-shaped working area of an interdigitated Ag-Pd alloy signal electrode. Field-emission scanning electron microscopy images confirmed the formation of homogeneous ZnO-NRs grown uniformly over the working area. X-ray diffraction revealed single-phase formation of ZnO-NRs, further confirmed by energy-dispersive X-ray spectroscopy analysis. Temperature-dependent impedance and modulus formalisms showed semiconductor-type behavior of ZnO-NRs. Two electro-active regions i.e., grain and grain boundary, were investigated which have activation energy ∼0.11 eV and ∼0.17 eV, respectively. The conduction mechanism was investigated in both regions using temperature-dependent AC conductivity analysis. In the low-frequency dispersion region, the dominant conduction is due to small polarons, which is attributed to the grain boundary response. At the same time, the correlated barrier hopping mechanism is a possible conduction mechanism in the high dispersion region attributed to the bulk/grain response. Moreover, substantial photoconductivity under UV light illumination was achieved which can be attributed to the high surface-to-volume ratio of zinc oxide nanorods as they provide high density of trap states which causes an increase in the carrier injection and movement leading to persistent photoconductivity. This photoconductivity was also facilitated by the frequency sweep applied to the sample which suggests the investigated ZnO nanorods based IDE devices can be useful for the application of efficient UV detectors. Experimental values of field lowering coefficient (ßexp) matched well with the theoretical value of ßS which suggests that the possible operating conduction mechanism in ZnO nanorods is Schottky type. I-V characteristics showed that the significantly high photoconductivity of ZnO-NRs as a result of UV light illumination is owing to the increase in number of free charge carriers as a result of generation of electron-hole pairs by absorption of UV light photons.

Roles and functions of SARS-CoV-2 proteins in host immune evasion.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the host immune system through a variety of regulatory mechanisms. The genome of SARS-CoV-2 encodes 16 non-structural proteins (NSPs), four structural proteins, and nine accessory proteins that play indispensable roles to suppress the production and signaling of type I and III interferons (IFNs). In this review, we discussed the functions and the underlying mechanisms of different proteins of SARS-CoV-2 that evade the host immune system by suppressing the IFN-ß production and TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3)/signal transducer and activator of transcription (STAT)1 and STAT2 phosphorylation. We also described different viral proteins inhibiting the nuclear translocation of IRF3, nuclear factor-κB (NF-κB), and STATs. To date, the following proteins of SARS-CoV-2 including NSP1, NSP6, NSP8, NSP12, NSP13, NSP14, NSP15, open reading frame (ORF)3a, ORF6, ORF8, ORF9b, ORF10, and Membrane (M) protein have been well studied. However, the detailed mechanisms of immune evasion by NSP5, ORF3b, ORF9c, and Nucleocapsid (N) proteins are not well elucidated. Additionally, we also elaborated the perspectives of SARS-CoV-2 proteins.

Comparative mutational analysis of SARS-CoV-2 isolates from Pakistan and structural-functional implications using computational modelling and simulation approaches.

SARS-CoV-2, an RNA virus, has been prone to high mutations since its first emergence in Wuhan, China, and throughout its spread. Its genome has been sequenced continuously by many countries, including Pakistan, but the results vary. Understanding its genomic patterns and connecting them with phenotypic features will help in devising therapeutic strategies. Thus, in this study, we explored the mutation landscape of 250 Pakistani isolates of SARS-CoV-2 genomes to check the genome diversity and examine the impact of these mutations on protein stability and viral pathogenesis in comparison with a reference sequence (Wuhan NC 045512.2). Our results revealed that structural proteins mainly exhibit more mutations than others in the Pakistani isolates; in particular, the nucleocapsid protein is highly mutated. In comparison, the spike protein is the most mutated protein globally. Furthermore, nsp12 was found to be the most mutated NSP in the Pakistani isolates and worldwide. Regarding accessory proteins, ORF3A is the most mutated in the Pakistani isolates, whereas ORF8 is highly mutated in world isolates. These mutations decrease the structural stability of their proteins and alter different biological pathways. Molecular docking, the dissociation constant (KD), and MM/GBSA analysis showed that mutations in the S protein alter its binding with ACE2. The spike protein mutations D614G-S943T-V622F (-75.17 kcal/mol), D614G-Q677H (-75.78 kcal/mol), and N74K-D614G (-73.84 kcal/mol) exhibit stronger binding energy than the wild type (-66.34 kcal/mol), thus increasing infectivity. Furthermore, the simulation results strongly corroborated the predicted protein servers. Our analysis findings also showed that E, M, ORF6, ORF7A, ORF7B, and ORF10 are the most stable coding genes; they may be suitable targets for vaccine and drug development.

Drug similarity and structure-based screening of medicinal compounds to target macrodomain-I from SARS-CoV-2 to rescue the host immune system: a molecular dynamics study.

The outbreak of the recent coronavirus (SARS-CoV-2), which causes a severe pneumonia infection, first identified in Wuhan, China, imposes significant risks to public health. Around the world, researchers are continuously trying to identify small molecule inhibitors or vaccine candidates by targeting different drug targets. The SARs-CoV-2 macrodomain-I, which helps in viral replication and hijacking the host immune system, is also a potential drug target. Hence, this study targeted viral macrodomain-I by using drug similarity, virtual screening, docking and re-docking approaches. A total of 64,043 compounds were screened, and potential hits were identified based on the docking score and interactions with the key residues. The top six hits were subjected to molecular dynamics simulation and Free energy calculations and repeated three times each. The per-residue energy decomposition analysis reported that these compounds significantly interact with Asp22, Ala38, Asn40, Val44, Phe144, Gly46, Gly47, Leu127, Ser128, Gly130, Ile131, Phe132 and Ala155 which are the critical active site residues. Here, we also used ADPr as a positive control to compare our results. Our results suggest that our identified hits by using such a complicated computational pipeline could inhibit the SARs-CoV-2 by targeting the macrodomain-1. We strongly recommend the experimental testing of these compounds, which could rescue the host immune system and could help to contain the disease caused by SARs-CoV-2.Communicated by Ramaswamy H. Sarma.

Preoperative management through modified halo-pelvic distraction assembly in a case of severe thoracic spine kyphosis.

BACKGROUND: Halo-traction device has been seen with favorable outcome in managing the patients with severe kyphotic deformities preoperatively, however, associated complications are inevitable. Slight modifications can improve the outcome and clinical efficacy. CASE DESCRIPTION: A 14-year-old boy was presented with severe kyphotic deformity of 141° from T1 to T10 thoracic vertebrae with diffuse paraspinal calcification in thoracic spine and complete loss of power of both lower limbs. A modified halo-pelvic distraction device was applied before the definitive surgery. The device comprised halo and pelvic assembly, the halo ring was connected to the head with 06 pins, while pelvic assembly had Ilizarov half pins connected to the arches. The assembly construct had four threaded rods, two of them were placed anterolateral and the other two were posterolateral. Distraction at the rate of 3 mm/day was started from 1st postoperative day for 35 days. The neurology improved in both lower limbs and kyphotic angle reduced to 56° from 141°. Surgery at this stage was done and a standalone solid titanium cage was placed from T1 to T10 vertebral body after debridement. No peri- or post-operative complications were observed. CONCLUSION: The application of halo-pelvic distraction before corrective surgeries can not only reduce the severity of the kyphotic deformity making the definitive surgery easy but neurology can also be improved. The high-risk complications associated with acute correction of deformities can be minimized using our modified halo-pelvic distraction device.

Mutations in SARS-CoV-2 ORF8 Altered the Bonding Network With Interferon Regulatory Factor 3 to Evade Host Immune System.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been continuously mutating since its first emergence in early 2020. These alterations have led this virus to gain significant difference in infectivity, pathogenicity, and host immune evasion. We previously found that the open-reading frame 8 (ORF8) of SARS-CoV-2 can inhibit interferon production by decreasing the nuclear translocation of interferon regulatory factor 3 (IRF3). Since several mutations in ORF8 have been observed, therefore, in the present study, we adapted structural and biophysical analysis approaches to explore the impact of various mutations of ORF8, such as S24L, L84S, V62L, and W45L, the recently circulating mutant in Pakistan, on its ability to bind IRF3 and to evade the host immune system. We found that mutations in ORF8 could affect the binding efficiency with IRF3 based on molecular docking analysis, which was further supported by molecular dynamics simulations. Among all the reported mutations, W45L was found to bind most stringently to IRF3. Our analysis revealed that mutations in ORF8 may help the virus evade the immune system by changing its binding affinity with IRF3.

Structural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System.

Mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have made this virus more infectious. Previous studies have confirmed that non-structural protein 13 (NSP13) plays an important role in immune evasion by physically interacting with TANK binding kinase 1 (TBK1) to inhibit IFNß production. Mutations have been reported in NSP13; hence, in the current study, biophysical and structural modeling methodologies were adapted to dissect the influence of major mutations in NSP13, i.e., P77L, Q88H, D260Y, E341D, and M429I, on its binding to the TBK1 and to escape the human immune system. The results revealed that these mutations significantly affected the binding of NSP13 and TBK1 by altering the hydrogen bonding network and dynamic structural features. The stability, flexibility, and compactness of these mutants displayed different dynamic features, which are the basis for immune evasion. Moreover, the binding was further validated using the MM/GBSA approach, revealing that these mutations have higher binding energies than the wild-type (WT) NSP13 protein. These findings thus justify the basis of stronger interactions and evasion for these NSP13 mutants. In conclusion, the current findings explored the key features of the NSP13 WT and its mutant complexes, which can be used to design structure-based inhibitors against the SARS-CoV-2 new variants to rescue the host immune system.

Plant growth regulators and EDTA improve phytoremediation potential and antioxidant response of Dysphania ambrosioides (L.) Mosyakin & Clemants in a Cd-spiked soil.

Soil pollution due to potentially toxic elements is a worldwide challenge for health and food security. Chelate-assisted phytoextraction along with the application of plant growth regulators (PGRs) could increase the phytoremediation efficiency of metal-contaminated soils. The present study was conducted to investigate the effect of different PGRs [Gibberellic acid (GA3) and indole acetic acid (IAA)] and synthetic chelator (EDTA) on growth parameters and Cd phytoextraction potential of Dysphania ambrosioides (L.) Mosyakin & Clemants grown under Cd-spiked soil. GA3 (10-7 M) and IAA (10-5 M) were applied four times with an interval of 10 days through a foliar spray, while EDTA (40 mg kg-1 soil) was once added to the soil. The results showed that Cd stress significantly decreased fresh biomass, dry biomass, total water contents, and photosynthetic pigments as compared to control. Application of PGRs significantly enhanced plant growth and Cd phytoextraction. The combined application of GA3 and IAA with EDTA significantly increased Cd accumulation (6.72 mg pot-1 dry biomass) and bioconcentration factor (15.21) as compared to C1 (Cd only). The same treatment significantly increased chlorophyll, proline, phenolic contents, and antioxidant activities (CAT, SOD, and POD) while MDA contents were reduced. In roots, Cd accumulation showed a statistically significant and positive correlation with proline, phenolics, fresh biomass, and dry biomass. Similarly, Cd accumulation showed a positive correlation with antioxidant enzyme activities in leaves. D. ambrosioides showed hyperaccumulation potential for Cd, based on bioconcentration factor (BCF) > 1. In conclusion, exogenous application of GA3 and IAA reduces Cd stress while EDTA application enhances Cd phytoextraction and ultimately the phytoremediation potential of D. ambrosioides.

In Silico Mutagenesis-Based Remodelling of SARS-CoV-1 Peptide (ATLQAIAS) to Inhibit SARS-CoV-2: Structural-Dynamics and Free Energy Calculations.

The prolific spread of COVID-19 caused by a novel coronavirus (SARS-CoV-2) from its epicenter in Wuhan, China, to every nook and cranny of the world after December 2019, jeopardize the prevailing health system in the world and has raised serious concerns about human safety. Multi-directional efforts are made to design small molecule inhibitors, and vaccines and many other therapeutic options are practiced, but their final therapeutic potential is still to be tested. Using the old drug or vaccine or peptides could aid this process to avoid such long experimental procedures. Hence, here, we have repurposed a small peptide (ATLQAIAS) from the previous study, which reported the inhibitory effects of this peptide. We used in silico mutagenesis approach to design more peptides from the native wild peptide, which revealed that substitutions (T2W, T2Y, L3R, and A5W) could increase the binding affinity of the peptide towards the 3CLpro. Furthermore, using MD simulation and free energy calculation confirmed its dynamics stability and stronger binding affinities. Per-residue energy decomposition analysis revealed that the specified substitution significantly increased the binding affinity at the residue level. Our wide-ranging analyses of binding affinities disclosed that our designed peptide owns the potential to hinder the SARS-CoV-2 and will reduce the progression of SARS-CoV-2-borne pneumonia. Our research strongly suggests the experimental and clinical validation of these peptides to curtail the recent corona outbreak.