Harnessing the power of hybrid deep learning algorithm for the estimation of global horizontal irradiance.

Accurately and precisely estimating global horizontal irradiance (GHI) poses significant challenges due to the unpredictable nature of climate parameters and geographical limitations. To address this challenge, this study proposes a forecasting framework using an integrated model of the convolutional neural network (CNN), long short-term memory (LSTM), and gated recurrent unit (GRU). The proposed model uses a dataset of four different districts in Rajasthan, each with unique solar irradiance patterns. Firstly, the data was preprocessed and then trained with the optimized parameters of the standalone and hybrid models and compared. It can be observed that the proposed hybrid model (CNN-LSTM-GRU) consistently outperformed all other models regarding Mean absolute error (MAE) and Root mean squared error (RMSE). The experimental results demonstrate that the proposed method forecasts accurate GHI with a RMSE of 0.00731, 0.00730, 0.00775, 0.00810 and MAE of 0.00516, 0.00524, 0.00552, 0.00592 for Barmer, Jaisalmer, Jodhpur and Bikaner respectively. This indicates that the model is better at minimizing prediction errors and providing more accurate GHI estimates. Additionally, the proposed model achieved a higher coefficient of determination (R (Ghimire et al., 2019)), suggesting that it best fits the dataset. A higher R2 value signifies that the proposed model could explain a significant portion of the variance in the GHI dataset, further emphasizing its predictive capabilities. In conclusion, this work demonstrates the effectiveness of the hybrid algorithm in improving adaptability and enhancing prediction accuracy for GHI estimation.

Graft Inflow Modulation by Splenic Artery Ligation for Portal Hyper Perfusion does not Decrease Rates of Early Allograft Dysfunction in Adult Live Donor Liver Transplantation: A Randomized Control Trial.

OBJECTIVE: The primary objective was to compare the rates of early allograft dysfunction (EAD) in patients undergoing elective adult live donor liver transplantation (ALDLT) with and without graft portal inflow modulation (GIM) for portal hyper-perfusion. The secondary objectives were to compare time to normalization of bilirubin and International Normalized Ratio (INR), day 14 ascitic output more than 1liter, small-for-size syndrome (SFSS), intensive care unit / high dependency unit and total hospital stay, and 90 day morbidity and mortality. BACKGROUND: GIM can prevent EAD in ALDLT patients with portal hyper-perfusion. METHODS: A single-center randomized trial with and without GIM for portal hyper-perfusion by splenic artery ligation (SAL) in ALDLT was performed. After reperfusion, patients with portal venous pressure (PVP)>15 mm Hg with a gradient (PVP - central venous pressure) of ≥ 7 mm Hg and/or portal venous flow (PVF)>250 mL/min/100 grams of liver were randomized into two groups: GIM and No GIM. RESULTS: 75 of 209 patients satisfied the inclusion criteria, and 38 underwent GIM. Baseline PVF and PVP were comparable between the GIM and no GIM groups. SAL significantly reduced the PVF and PVP (P<0.001). There were no differences in the primary and secondary outcomes between the two groups. In the subgroup analysis, with a Graft to Recipient Weight Ratio (GRWR)≤0.8, there were no significant differences in the primary and secondary outcomes. CONCLUSION: SAL significantly decreased PVP and PVF, but did not decrease rates of EAD in adult LDLT.

Anemia Awareness Program in a Suburban Middle School: A Pilot Study Promoting Students as Public Health Advocates in Their Community.

INTRODUCTION: Almost a quarter of the people on earth are anemic, and most of them reside in regions of sub-Saharan Africa and South Asia. Anemia in children is linked with impaired cognitive and motor development and affects the future earning capacity. The most common cause of anemia is iron deficiency. The Indian Government has initiated multiple programs for the eradication of anemia. The prevalence of anemia has not decreased despite the improvements in the country's economy. It increased from 58.7% in 2015-16 to 67.1% in 2019-21 in children and from 50.4% in 2015-16 to 52.2% in 2019-21 in pregnant women. Maternal education, socioeconomic status, and number of children in the family are some factors that influence the prevalence of anemia. As these factors cannot be improved in a short time, we aimed to increase awareness about this issue by targeting school students from rural/semi-urban backgrounds. METHODS: This pilot study aimed at promoting school students as public health advocates in their community. Anemia Awareness Program was conducted in a local middle school in the suburban area, which was attended by 153 class eight students (72 female). Pre- and post-test questionnaires comprising 20 multiple-choice/true-false type questions were used. Pre- and post-test scores were obtained. The second part of the study was the identification of students with anemia. Blood hemoglobin levels of 127 students (58 female) were measured from venous blood samples. The students were also asked to inform their friends/relatives about anemia and to send people with symptoms of anemia to the free two-day Anemia Awareness Camp organized by the Medical College Hospital for check-ups. RESULTS: The mean post-test score (15.68/20) was much higher than the pretest score (2.99/20). Thirty-eight (25 female) out of 127 students had mild/moderate microcytic hypochromic anemia, suggesting iron deficiency. Thirty-two persons visited the free health camp to receive information from the students, of whom four had normal hemoglobin levels. CONCLUSION: This pilot study showed that physician-conducted anemia awareness programs are relatively low-cost methods to spread information among the general population in India.

Assessing variability in non-contrast CT for the evaluation of stroke: The effect of CT image reconstruction conditions on AI-based CAD measurements of ASPECTS value and hypodense volume.

Purpose: To rule out hemorrhage, non-contrast CT (NCCT) scans are used for early evaluation of patients with suspected stroke. Recently, artificial intelligence tools have been developed to assist with determining eligibility for reperfusion therapies by automating measurement of the Alberta Stroke Program Early CT Score (ASPECTS), a 10-point scale with > 7 or ≤ 7 being a threshold for change in functional outcome prediction and higher chance of symptomatic hemorrhage, and hypodense volume. The purpose of this work was to investigate the effects of CT reconstruction kernel and slice thickness on ASPECTS and hypodense volume. Methods: The NCCT series image data of 87 patients imaged with a CT stroke protocol at our institution were reconstructed with 3 kernels (H10s-smooth, H40s-medium, H70h-sharp) and 2 slice thicknesses (1.5mm and 5mm) to create a reference condition (H40s/5mm) and 5 non-reference conditions. Each reconstruction for each patient was analyzed with the Brainomix e-Stroke software (Brainomix, Oxford, England) which yields an ASPECTS value and measure of total hypodense volume (mL). Results: An ASPECTS value was returned for 74 of 87 cases in the reference condition (13 failures). ASPECTS in non-reference conditions changed from that measured in the reference condition for 59 cases, 7 of which changed above or below the clinical threshold of 7 for 3 non-reference conditions. ANOVA tests were performed to compare the differences in protocols, Dunnett's post-hoc tests were performed after ANOVA, and a significance level of p < 0.05 was defined. There was no significant effect of kernel (p = 0.91), a significant effect of slice thickness (p < 0.01) and no significant interaction between these factors (p = 0.91). Post-hoc tests indicated no significant difference between ASPECTS estimated in the reference and any non-reference conditions. There was a significant effect of kernel (p < 0.01) and slice thickness (p < 0.01) on hypodense volume, however there was no significant interaction between these factors (p = 0.79). Post-hoc tests indicated significantly different hypodense volume measurements for H10s/1.5mm (p = 0.03), H40s/1.5mm (p < 0.01), H70h/5mm (p < 0.01). No significant difference was found in hypodense volume measured in the H10s/5mm condition (p = 0.96). Conclusion: Automated ASPECTS and hypodense volume measurements can be significantly impacted by reconstruction kernel and slice thickness.

Unraveling the anti-breast cancer activity of Cimicifugae rhizoma using biological network pathways and molecular dynamics simulation.

Cimicifugae is a commonly used treatment for breast cancer, but the specific molecular mechanisms underlying its effectiveness remain unclear. In this research, we employ a combination of network pharmacology, molecular docking, and molecular dynamics simulations to uncover the most potent phytochemical within Cimicifugae rhizoma in order to delve into its interaction with the target protein in breast cancer treatment. We identified 18 active compounds and 89 associated targets, primarily associated to various biological processes such as lipid metabolism, the signaling pathway in diabetes, viral infections, and cancer-related pathways. Molecular docking analysis revealed that the two most active compounds, Formononetin and Cimigenol, exhibit strong binding to the target protein AKT1. Through molecular dynamics simulations, we found that the Cimigenol-AKT1 complex exhibits greater structural stability and lower interaction energy compared to the stigmasterol-AKT1 complex. Our study demonstrates that Cimicifugae rhizoma exerts its effects in breast cancer treatment through a multi-component, multi-target synergistic approach. Furthermore, we propose that Cimigenol, targeting AKT-1, represents the most effective compound, offering valuable insights into the molecular mechanisms underpinning its role in breast cancer therapy.

Giant Calcified Hepatic Hydatid Cyst: A Case Report.

Hydatid disease is a zoonotic disease caused by the parasite Echinococcus granulosus. It is an endemic disease in many parts of the world. Although humans are incidental hosts of the parasite, the disease sometimes results in fatal consequences. The liver and lungs are the most common sites of infection in humans. We report the case of a 45-year-old female who presented with complaints of right hypochondriac pain, fever, and cough, initially suspected as a case of liver abscess but later diagnosed as a giant calcified hydatid cyst of the liver. Imaging and immunoglobulin G for Echinococcus granulosus helped confirm our diagnosis. Based on her symptoms, the patient was treated symptomatically with analgesics, paracetamol, and an antitussive for pain, fever, and cough, respectively. In terms of definitive care, she was treated with oral albendazole and referred to her home district for necessary surgical intervention.

PHA-665752's Antigrowth and Proapoptotic Effects on HSC-3 Human Oral Cancer Cells.

c-Met is a tyrosine-kinase receptor, and its aberrant activation plays critical roles in tumorigenesis, invasion, and metastatic spread in many human tumors. PHA-665752 (PHA) is an inhibitor of c-Met and has antitumor effects on many hematological malignancies and solid cancers. However, the activation and expression of c-Met and its role and the antitumor effect of PHA on human oral squamous cell carcinoma (OSCC) cells remain unclear. Here, we investigated the activation and expression of c-Met and the effects of PHA on the growth of a highly tumorigenic HSC-3 human OSCC cell line with high c-Met phosphorylation and expression. Of note, c-Met was highly expressed and phosphorylated on Y1234/1235 in HSC-3 cells, and PHA treatment significantly suppressed the growth and induced apoptosis of these cells. Moreover, PHA that inhibited the phosphorylation (activation) of c-Met further caused the reduced phosphorylation and expression levels of Src, protein kinase B (PKB), mammalian target of rapamycin (mTtor), and myeloid cell leukemia-1 (Mcl-1) in HSC-3 cells. In addition, the antiangiogenic property of PHA in HSC-3 cells was shown, as evidenced by the drug's suppressive effect on the expression of hypoxia-inducible factor-1α (HIF-1α), a critical tumor angiogenic transcription factor. Importantly, genetic ablation of c-Met caused the reduced growth of HSC-3 cells and decreased Src phosphorylation and HIF-1α expression. Together, these results demonstrate that c-Met is highly activated in HSC-3 human oral cancer cells, and PHA exhibits strong antigrowth, proapoptotic, and antiangiogenic effects on these cells, which are mediated through regulation of the phosphorylation and expression of multiple targets, including c-Met, Src, PKB, mTOR, Mcl-1, and HIF-1α.

Nanocomposite Marvels: Unveiling Breakthroughs in Photocatalytic Water Splitting for Enhanced Hydrogen Evolution.

An overview of the significant innovations in photocatalysts for H2 development, photocatalyst selection criteria, and photocatalytic modifications to improve the photocatalytic activity was examined in this Review, as well as mechanisms and thermodynamics. A variety of semiconductors have been examined in a structured fashion, such as TiO2-, g-C3N4-, graphene-, sulfide-, oxide-, nitride-, oxysulfide-, oxynitrides, and cocatalyst-based photocatalysts. The techniques for enhancing the compatibility of metals and nonmetals is discussed in order to boost photoactivity within visible light irradiation. In particular, further deliberation has been carried out on the development of heterojunctions, such as type I, type II, and type III, along with Z-systems, and S-scheme systems. It is important to thoroughly investigate these issues in the sense of visible light irradiations to enhance the efficacy of photocatalytic action. In fact, another advancement in this area may include hiring mediators including grapheme oxide and metals to establish indirect Z-scheme montages with a correct band adjustment. The potential consideration of reaction chemology, mass transfer, kinetics of reactions, restriction of light diffusion, and the process and selection of suitable light and photoreactor also will optimize sustainable hydrogen output efficiency and selectivity.

Paper-Based Flexible Nanoparticle Hybrid Substrate for Qualitative and Quantitative Analysis of Melamine in Powder Milk by SERS.

Melamine is a chemical compound that is added to dairy products to increase the apparent protein content for higher profit margins. However, extended consumption of melamine can cause health risks. The SERS technique has proven to be an important tool for detecting small compounds, such as melamine. Here, a paper-based flexible nanoparticles (NPs)-hybrid SERS substrate was designed by drop-casting pegylated gold nanoparticles (AuNPs) on the filter papers. In SERS characterization, this substrate exhibited an enhancement factor of 108 and a limit of detection (LOD) as low as 10-8 M for Rhodamine 6G dye. Furthermore, we successfully utilized these substrates to detect the melamine spiked milk sample with an LOD as low as 0.01 ppm. This hybrid SERS substrate offers a low-cost, biocompatible, and easy-to-use fabrication for large-scale production, which may be widely used in food safety applications.

Temporary Portocaval Shunt Provides Superior Intraoperative Hemodynamics and Reduces Blood Loss and Duration of Surgery in Live Donor Liver Transplantation: A Randomized Control Trial.

OBJECTIVE: To compare intraoperative hemodynamic parameters, blood loss, renal function, and duration of surgery with and without temporary portocaval shunt (TPCS) in live donor liver transplantation (LT) recipients. Secondary objectives were postoperative early graft dysfunction, morbidity, mortality, total intensive care unit, and hospital stay. BACKGROUND: Blood loss during recipient hepatectomy for LT remains a major concern. Routine use of TPCS during LT is not yet elucidated. METHODS: This study is a single-center, open-label, randomized control trial. The sample size was calculated based on intraoperative blood loss. After exclusion, a total of 60 patients, 30 in each arm (TPCS vs no TPCS) were recruited in the trial. RESULTS: The baseline recipient and donor characteristics were comparable between the groups. The median intraoperative blood loss ( P = 0.004) and blood product transfusions ( P < 0.05) were significantly less in the TPCS group. The TPCS group had significantly improved intraoperative hemodynamics in the anhepatic phase as compared with the no TPCS group ( P < 0.0001), requiring significantly less vasopressor support. This led to significantly better renal function as evidenced by higher intraoperative urine output in the TPCS group ( P = 0.002). Because of technical simplicity, the TPCS group had significantly fewer inferior vena cava injuries (3.3 vs 26.7%, P = 0.026) and substantially shorter hepatectomy time and total duration of surgery (529.4 ± 35.54 vs 606.83 ± 48.13 min, P < 0.0001). The time taken for normalization of lactate in the immediate postoperative period was significantly shorter in the TPCS group (median, 6 vs 13 h; P = 0.04). Although postoperative endotoxemia, major morbidity, 90-day mortality, total intensive care unit, and hospital stay were comparable between both groups, tolerance to enteral feed was earlier in the TPCS group. CONCLUSIONS: In live donor LT, TPCS is a simple and effective technique that provides superior intraoperative hemodynamics and reduces blood loss and duration of surgery.

Repurposing integrase inhibitors against human T-lymphotropic virus type-1: a computational approach.

Adult T-cell Lymphoma (ATL) is caused by the delta retrovirus family member known as Human T-cell Leukaemia Type I (HTLV-1). Due to the unavailability of any cure, the study gained motivation to identify some repurposed drugs against the virus. A quick and accurate method of screening licensed medications for finding a treatment for HTLV-1 is by cheminformatics drug repurposing in order to analyze a dataset of FDA approved integrase antivirals against HTLV-1 infection. To determine how the antiviral medications interacted with the important residues in the HTLV-1 integrase active regions, molecular docking modeling was used. The steady behavior of the ligands inside the active region was then confirmed by molecular dynamics for the probable receptor-drug complexes. Cabotegravir, Raltegravir and Elvitegravir had the best docking scores with the target, indicating that they can tightly bind to the HTLV-1 integrase. Moreover, MD simulation revealed that the Cabotegravir-HTLV-1, Raltegravir-HTLV-1 and Elvitegravir-HTLV-1 interactions were stable. It is obvious that more testing of these medicines in both clinical trials and experimental tests is necessary to demonstrate their efficacy against HTLV-1 infection.Communicated by Ramaswamy H. Sarma.

Ecosystem-based fishery enhancement through pen culture of Indian major carp Labeo catla in a tropical floodplain wetland of North Eastern Region, India, during COVID pandemic.

The present study was conducted with the objective of developing ecologically and economically feasible pen culture protocols for Labeo catla as an alternate income source for wetland fishers in the context of the COVID-19 pandemic. Yearlings of L. catla (12.33 ± 1.99 cm mean total length and 26.05 ± 6.57 g mean weight) were reared in HDPE pens (500 m2 area each) at three different stocking densities of 3 (SD3), 6 (SD6) and 9 (SD9) no. m-2 in triplicates. Fishes were fed with floating pelleted feed containing 28% crude protein and 5% crude lipid two times daily at 1.5-3% of body weight. During the culture period, fish grew from 26.05 ± 6.57 to 434.61 ± 30.63 g, 306.13 ± 10.68 g and 221.13 ± 14.92 g, respectively, at stocking densities of 3, 6 and 9 no. m-2 respectively. Weight gain percentage and specific growth rate declined with increase in stocking density. Gross fish yield increased with increase in stocking density and was highest at SD9 (657.92 ± 53.55 kg pen-1), while net fish yield increased initially from SD3 to SD6 (594.31 ± 29.72 kg pen-1) and then declined with further increase in stocking density. Important water quality parameters influencing fish growth were measured, and significant difference (p > 0.05) was not observed between treatments (inside pens) and reference site (outside pen at 10-m distance). Weight gain was positively correlated (p < 0.05) to water temperature (r = 0.989) and total phosphorus (r = 0.81). Benefit cost ratio and net return was highest at SD3 (1.61; US $518.88, respectively). Stocking density of 3 no. m-2 can be considered economically feasible for table fish production of L. catla in pens. Post pen culture, monthly income of fishers increased by 10.76-179.11%, with a mean increase of 90.57%, compared to the period of first COVID-19 wave in India. The present findings can provide an impetus for effective utilization of pen enclosures for income generation and livelihood enhancement of small-scale wetland fishers during pandemic.

Predictive Factors Influencing the Return to Sports Following Arthroscopic Knee Meniscectomy in Sports Persons: A Prospective Cohort Study.

Meniscus tears are among the common knee injuries in sports, with arthroscopic meniscectomy being one of the most commonly performed orthopedic procedures. Return to sports of the same level following arthroscopic meniscectomy is an important aspect for athletes. Numerous factors may influence the time required for athletes to resume sports activities after meniscectomy. This prospective cohort study aimed to investigate the timeframe for returning to sports in athletes who underwent arthroscopic meniscectomy and to identify predictive factors that influence this return. Ninety sports persons who had undergone arthroscopic meniscectomy were included in this study. The patients were analyzed for their time to return to sports and nine proposed predictive factors that may influence their return to sports. Out of the 90 participants, 75 were able to return to their previous activity level, while the remaining 15 were unable to do so. Among the nine pre-defined factors studied, age older than 25 years (p < 0.0001), participation in non-contact sports (p < 0.0001), and engagement in recreational activities (p < 0.0001) were found to be statistically significant. In conclusion, this study reveals that with the increase in age, time to return to sports following arthroscopic meniscectomy increases. Additionally, athletes involved in non-contact sports and those having recreational sports activity levels experience greater delays in their return to sports as compared to athletes involved in combat and contact sports and athletes having elite and competitive sports levels, respectively.

Molecular docking, molecular dynamics and binding free energy based identification of novel potential multitarget inhibitors of Nipah virus.

Nipah virus (NiV) is one of the most common viral diseases affecting the brain and nervous system of the body. To date, there is no significant antiviral drug specifically designed to inhibit NiV. In the last ten years, there has been a significant increase in interest in multitarget drug development. Therefore, the reported work focuses on designing a multitarget inhibitor for NiV. Among the twelve designed compounds, five exhibited better drug-likeness and ADMET properties, hence being selected for further analysis. In a molecular docking study, these compounds possessed better binding affinity as compared to Favipiravir. The RMSD of these compounds was ≤2Å and the number of H-bonds signified the better stability of the complexes formed. The ΔGbind of C4, C6 and C7 was found to be comparatively higher than the other screened compounds, revealing their greater ability to bind efficiently with NiV-G, NiV-F and NiV-N receptors, respectively. Therefore, based on molecular docking, molecular dynamics, and MM/PBSA analysis, these compounds can act as potential inhibitors of multitargets of NiV.Communicated by Ramaswamy H. Sarma.

A graphene-based material for green sustainable energy technology for hydrogen storage.

The usage of graphene-based materials (GMs) as energy storage is incredibly popular. Significant obstacles now exist in the way of the generation, storage and consumption of sustainable energy. A primary focus in the work being done to advance environmentally friendly energy technology is the development of effective energy storage materials. Due to their distinct two-dimensional structure and intrinsic physical qualities like good electrical conductivity and wide area, graphene-based materials have a significant potential to be used in energy storage devices. Graphene and GMs have been employed extensively for this due to their special mechanical, thermal, catalytic and other functional qualities. In this review, we covered the topic of employing GMs to store hydrogen for green energy.

Tailoring pretext tasks to improve self-supervised learning in histopathologic subtype classification of lung adenocarcinomas.

Lung adenocarcinoma (LUAD) is a morphologically heterogeneous disease with five predominant histologic subtypes. Fully supervised convolutional neural networks can improve the accuracy and reduce the subjectivity of LUAD histologic subtyping using hematoxylin and eosin (H&E)-stained whole slide images (WSIs). However, developing supervised models with good prediction accuracy usually requires extensive manual data annotation, which is time-consuming and labor-intensive. This work proposes three self-supervised learning (SSL) pretext tasks to reduce labeling effort. These tasks not only leverage the multi-resolution nature of the H&E WSIs but also explicitly consider the relevance to the downstream task of classifying the LUAD histologic subtypes. Two tasks involve predicting the spatial relationship between tiles cropped from lower and higher magnification WSIs. We hypothesize that these tasks induce the model to learn to distinguish different tissue structures presented in the images, thus benefiting the downstream classification. The third task involves predicting the eosin stain from the hematoxylin stain, inducing the model to learn cytoplasmic features relevant to LUAD subtypes. The effectiveness of the three proposed SSL tasks and their ensemble was demonstrated by comparison with other state-of-the-art pretraining and SSL methods using three publicly available datasets. Our work can be extended to any other cancer type where tissue architectural information is important. The model could be used to expedite and complement the process of routine pathology diagnosis tasks. The code is available at https://github.com/rina-ding/ssl_luad_classification.

Identification of 3, 4-dihydroxy complexes as potential antiviral via DFT, molecular docking, molecular dynamics and MM/PBSA against rabies and dengue receptors.

The quest to identify antiviral drug candidates for dengue and rabies viral diseases is a great challenge for the researchers. While different research is being conducted on the repurposed drugs against these two viruses, no drug compound has gained success in treating them. Therefore, in this study, 3, 4-dihydroxy complexes have been virtually designed to investigate their antiviral properties and analyze their efficiency in interaction with the concerned viral diseases. DFT calculations are carried out to study the electronic and thermodynamic properties to understand the stability and reactivity of the reported compounds. These compounds were subjected to molecular docking studies to understand the binding interactions with NS5 Dengue virus mRNA 2'-O-methyltransferase and phosphoprotein C-terminal domain of Rabies virus. MD simulation, hydrogen bond analysis, and MM/PBSA were performed at 100 ns to support the obtained docking results.Communicated by Ramaswamy H. Sarma.

In silico identification of cyclosporin derivatives as potential inhibitors for RdRp of rotavirus by molecular docking and molecular dynamic studies.

Rotavirus is one of the most common gastrointestinal viral diseases. Till date, there are only two vaccines available in the markets, which are specifically to be administered to young babies. In this study, VP1 RdRp is selected as potential target to carry out inhibitory activities. Cyclosporin A (Cys A) derivatives were designed via FBDD, pharmacokinetics, molecular docking, molecular dynamics (MD) simulation and molecular mechanics generalized born surface area was applied on these compounds. The results from these investigations were analyzed and it was found that the considered derivatives in this study were nontoxic and docking results revealed that the derivatives made some important bonds inside the active site of the receptors within a catalytic triad (Serine-Histidine-Aspartate). After analyzing the mean values of root mean square density (RMSD), root mean square fluctuation (RMSF), radius of gyration (RoG) and solvent accessible surface area (SASA) at 100 ns MD simulation of the selected compounds, it was found that compound 1 exhibits RMSD of 0.74 ± 0.10 Å, RMSF of 0.85 ± 0.15 Å, RoG of 16.45 ± 0.40 Å, SASA of 66.55 ± 0.35 nm2 and ΔGbind of -32.76 ± 0.02 kcal/mol. Therefore, the study revealed that amongst the designed and reported compounds, compound 1 was more stable within the active region of the RdRp and also this compound possesses lower binding free energy as compared to other selected compounds and Cys A as well.Communicated by Ramaswamy H. Sarma.

In silico identification and molecular dynamic simulations of derivatives of 6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide against main protease 3CLpro of SARS-CoV-2 viral infection.

CONTEXT: The unavailability of target-specific antiviral drugs for SARS-CoV-2 viral infection kindled the motivation to virtually design derivatives of 6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide as potential antiviral inhibitors against the concerned virus. The molecular docking and molecular dynamic results revealed that the reported derivatives have a potential to act as antiviral drug against SARS-CoV-2. The reported hit compounds can be considered for in vitro and in vivo analyses. METHODS: Fragment-based drug designing was used to model the derivatives. Furthermore, DFT simulations were carried out using B3LYP/6-311G** basis set. Docking simulations were performed by using a combination of empirical free energy force field with a Lamarckian genetic algorithm under AutoDock 4.2. By the application of AMBER14 force field and SPCE water model, molecular dynamic simulations and MM-PBSA were calculated for 100 ns.