Comparative Structural Analysis Research Articles

Time history comparative analyses of a thin-walled cold-formed steel structure considering P-D effect

The paper presents a comparative time history analysis based on the 1D-beam Finite Element Method (FEM) for a thin-walled cold-formed steel structure previously investigated both theoretically and experimentally. The recent earthquake which occurred in Turkey with 7.8Mw and a Peak Ground Acceleration (PGA) of almost 0.5g showed numerous collapses of different types of buildings. Romania has an active seismic area located in the Vrancea region where, in 1977 a 7.5Mw earthquake also occurred. In this context, this paper presents a comparative analysis with time history accelerograms of the recorded earthquake in North – South and East - West directions. The structural model was analyzed in Robot Structural Analysis software in two scenarios of the time history accelerograms considering also the P-Δ effect. The finite elements of the structure were defined as 1-D beam elements with hinged joints and limited axial stiffness previously obtained in past studies. The results showed a substantial increase in terms of displacements and stresses.

On Text Understanding Modeling by Means of Artificial Intelligence Systems

Purpose of reseach is to conduct a comparative analysis of texts generated by an artificial intelligence system in the process of processing source text in natural language and counter texts that are the result of human understanding of the source literary text. Methods. To achieve the goal and objectives of the study, the author used an experimental technique to conduct a comparative analysis of the denotational structures of counter texts. Participants in the experiment (7 4th year students of the Faculty of Additional Education “Translator in the field of professional communications”, 3 associate professors of the Department of Foreign Languages of South- West State University) assessed the success of recreating the semantic structure of the text of 10 counter texts of different nature - generated by AI and humans. Results. The results of the experiment indicate that the completeness of the semantic content of the generated text does not depend on the structure of the source text. Modern methods of semantic text processing by an AI system make it possible to obtain the output of full-fledged text works created taking into account the rules and norms of natural language.AI systems successfully recreate the denotational structure of the text and reconstruct the syntactic structure. Conclusion. Access to large databases allows you to train a neural network on large text corpora, which results in an increase in the accuracy and variability of the lexical units and constructs used. The accuracy of conveying the semantic content of the text varies. It depends on the degree of text compression - the higher it is, the less accuracy can be, because the neural network is unable to classify denotational connections for relevance to the underlying meaning. The degree of accuracy in conveying semantic content is determined by the success / failure of understanding the deep hidden meaning, which is determined by the understanding of the linguistic and extralinguistic context. The ability to recognize the situation model recreated in the source text is the key to understanding the hidden meaning. The AI system can recreate the surface denotational structure of the text quite correctly and accurately, but is not able to construct a model of the situation at this stage of development.

Comparative structural analysis of MecA encoded beta-lactam resistance in MRSA

As the level of antibiotic resistance in bacteria rises, the threat of patients facing fatal consequences from a simple cut or infection grows dramatically. One example of an emerging antibiotic-resistant threat is MRSA, methicillin-resistant staphylococcus aureus, which is a growing cause of hospital-acquired pneumonia, skin infections, and even sepsis through cross-contamination in health care settings. However, methicillin resistance like that exploited by MRSA is also highly conserved with that of another species of staphylococcus bacteria, Staphylococcus sciuri which is the ancestral bacterium of S. aureus. S. sciuri is a typically animal-associated bacterium with increasing clinical relevance as the amount of human infections from it has grown. Both these bacteria share the commonality of having the mecA gene that determines methicillin resistance transported through the mobile Staphylococcal cassette chromosome. This study focuses on the relationship between the mecA mobile element in S. sciuri compared to S. aureus and explores the specific role of S. sciuri in the creation of the mecA cassette. Understanding the cassette evolution and similarities and differences between S. sciuri and S. aureus will enable the continued tracking of S. sciuri as an emerging clinical threat. To answer all these questions, BLAST analysis, InterProScan, and additional computational analysis were used to characterize differences in homology, structure, function, and effect on infectivity, robustness of antibiotic resistance, and morbidity. The overall goal of this analysis is to characterize the differences between mecA and methicillin-resistant genes in clinically relevant MRSA as well as environmental samples such as S. sciuri.

Comparative analysis of sleep parameters and structures derived from wearable flexible electrode sleep patches and polysomnography in young adults.

Polysomnography (PSG) is the gold standard for clinical sleep monitoring, but its cost, discomfort, and limited suitability for continuous use present challenges. The flexible electrode sleep patch (FESP) emerges as an economically viable and patient-friendly solution, offering lightweight, simple operation, and self-applicable. Nevertheless, its utilization in young individuals remains uncertain. The objective of this study was to compare sleep data obtained by FESP and PSG in healthy young individuals and analyze agreement for sleep parameters and structure classification. Overnight monitoring with FESP and PSG recordings in 48 participants (mean age: 23 yr) was done. Correlation analysis, Bland-Altman plots, and Cohen's kappa coefficient assessed consistency. Sensitivity, specificity, and predictive values compared classification against PSG. FESP showed strong correlation and consistency with PSG for sleep monitoring. Bland-Altman plots indicated small errors and high consistency. Kappa values (0.70-0.84) suggested substantial agreement for sleep stage classification. Pearson correlation coefficient values for sleep stages (0.75-0.88) and sleep parameters (0.80-0.96) confirm that FESP has a strong application. Intraclass correlation coefficient yielded values between 0.65 and 0.97. In addition, FESP demonstrated an impressive accuracy range of 84.12-93.47% for sleep stage classification. The FESP also features a wearable self-test program with an error rate of no more than 8% for both deep sleep and wake. In young adults, FESP demonstrated reliable monitoring capabilities comparable to PSG. With its low cost and user-friendly design, FESP is a potential alternative for portable sleep assessment in clinical and research applications. Further studies involving larger populations are needed to validate its diagnostic potential.NEW & NOTEWORTHY By comparison with PSG, this study confirmed the reliability of an efficient, objective, low-cost, and noninvasive portable automatic sleep-monitoring device FESP, which provides effective information for long-term family sleep disorder diagnosis and sleep quality monitoring.

AlphaFold2 Reveals Structural Patterns of Seasonal Haplotype Diversification in SARS-CoV-2 Spike Protein Variants.

The slow experimental acquisition of high-quality atomic structures of the rapidly changing proteins of the COVID-19 virus challenges vaccine and therapeutic drug development efforts. Fortunately, deep learning tools such as AlphaFold2 can quickly generate reliable models of atomic structure at experimental resolution. Current modeling studies have focused solely on definitions of mutant constellations of Variants of Concern (VOCs), leaving out the impact of haplotypes on protein structure. Here, we conduct a thorough comparative structural analysis of S-proteins belonging to major VOCs and corresponding latitude-delimited haplotypes that affect viral seasonal behavior. Our approach identified molecular regions of importance as well as patterns of structural recruitment. The S1 subunit hosted the majority of structural changes, especially those involving the N-terminal domain (NTD) and the receptor-binding domain (RBD). In particular, structural changes in the NTD were much greater than just translations in three-dimensional space, altering the sub-structures to greater extents. We also revealed a notable pattern of structural recruitment with the early VOCs Alpha and Delta behaving antagonistically by suppressing regions of structural change introduced by their corresponding haplotypes, and the current VOC Omicron behaving synergistically by amplifying or collecting structural change. Remarkably, haplotypes altering the galectin-like structure of the NTD were major contributors to seasonal behavior, supporting its putative environmental-sensing role. Our results provide an extensive view of the evolutionary landscape of the S-protein across the COVID-19 pandemic. This view will help predict important regions of structural change in future variants and haplotypes for more efficient vaccine and drug development.

A comparative analysis of soil physicochemical properties and microbial community structure among four shelterbelt species in the northeast China plain.

The focal point of this study lies in the implementation of a controlled experiment conducted under field conditions. In this experiment, we deliberately selected four shelterbelts within the same field, characterized by identical planting density, and planting year. This deliberate selection effectively mitigated the potential impact of extraneous factors on the three microbiomes, thereby enhancing the reliability and validity of our findings.

Interferon-induced protein with tetratricopeptide repeats 5 of black fruit bat (Pteropus alecto) displays a broad inhibition of RNA viruses.

Bats are natural host reservoirs and have adapted a unique innate immune system that permits them to host many viruses without exhibiting symptoms. Notably, bat interferon stimulated genes (ISGs) have been shown to play antiviral roles. Interferon induced protein with tetratricopeptide repeats 5 (IFIT5) is a well-characterised ISG in humans with antiviral activities against negative-sense RNA viruses via inhibiting viral transcription. Here, we aim to investigate if Pteropus alecto (pa) IFIT5 (paIFIT5) possess the ability to inhibit negative-sense RNA viruses. Initially, gene syntenic and comparative structural analyses of multiple animals highlighted a high level of similarity between Pteropus alecto and human IFIT5 proteins. Our results showed that paIFIT5 was significantly inducible by viral and dsRNA stimulation. Transient overexpression of paIFIT5 inhibited the replication of vesicular stomatitis virus (VSV). Using minireplicon and transcription reporter assays, we demonstrated the ability of paIFIT5 specifically to inhibit H17N10 polymerase activity. Mechanistically, we noticed that the antiviral potential of paIFIT5 against negative sense RNA viruses was retributed to its interaction with 5'ppp containing RNA. Taken together, these findings highlight the genetic and functional conservation of IFIT5 among mammals.

Comparative analysis of patellar tendon, achilles tendon and plantar fascia structure in indoor and outdoor football players: a novel cross-sectional pilot study

Different sport modalities were associate with tendon adaptation or even tendon disturbances, such as volleyball, soccer or basketball. Purpose: the aim of the present study was to determine de difference between indoor and outdoor football players on patellar tendon (PT), Achilles tendon (AT), plantar fascia (FP) and Hoffa’s fat pad thickness assessed with ultrasound imaging (USI). A cross-sectional study was developed with a total sample of 30 soccer players divided in two groups: outdoor group (n = 15) and indoor group (n = 15). The thickness of PT, AT, PF and Hoffa’s fat pad has been assessed with USI. Hoffa’s fat pad reported significant differences for the left side between groups (P = 0.026). The rest of variables did not show any significant difference (P < 0.05). The ultrasonography assessment of the thickness of the PT, AT and PF did not show differences between outdoor and indoor football players. Hoffa’s fat pad resulted showed a significant decrease for outdoor soccer players with respect futsal players. Thus, it can be considered that the load stimuli received in both soccer players were not enough to produce structural adaptations in PT, AT and PF tissues.

Comparative Analysis of Vascular Structures in OLIF51 and the Lateral Corridor Approach under Supine MRI and Intraoperative Enhanced CT in the Lateral Decubitus Position.

Background and Objectives: As the oblique lateral interbody fusion at L5/S1 (OLIF51) and the lateral corridor approach (LCA) have gained popularity, an understanding of the precise vascular structure at the L5/S1 level is indispensable. The objectives of this study were to investigate the vascular anatomy at the L5/S1 level, and to compare the movement of vascular tissue between the supine and lateral decubitus positions using intraoperative enhanced CT and MRI. Materials and Methods: A total of 43 patients who underwent either OLIF51 or LCA were investigated with an average age at surgery of 60.4 (37-80) years old. The preoperative MRI was taken to observe the axial and sagittal anatomy of the vascular position under the supine position. The intraoperative vein-enhanced CT was taken just before incision in the right decubitus position, and compared to supine MRI anatomy. Iliolumbar vein appearance and its types were also classified. Results: The average vascular window allowed for OLIF51 was 22.8 mm and 34.1 mm at either the L5 caudal endplate level or the S1 cephalad endplate level, respectively. The LCA was 14.2 mm and 12.6 mm at either level, respectively. The left common iliac vein moved 3.8 mm and 6.9 mm to the right direction at either level from supine to the right decubitus position, respectively. The bifurcation moved 6.3 mm to the caudal direction from supine to right decubitus. The iliolumbar vein was located at 31 mm laterally from the midline, and the MRI detection rate was 52%. Conclusions: The precise measurement of vascular anatomy indicated that the OLIF51 approach was the standard minimally invasive anterior approach for the L5/S1 disc level compared to LCA; however, there were many variations in quantitative anatomy as well as significant vascular movements between the supine and right decubitus positions. In the clinical setting of OLIF51 and LCA surgeries, careful preoperative evaluation and intraoperative 3D imaging are recommended for safe and accurate surgery.

Biochemical and Structural Studies of LjSK1, a Lotus japonicus GSK3β/SHAGGY-like Kinase, Reveal Its Functional Role.

The crystal structure of a truncated form of the Lotus japonicus glycogen synthase kinase 3β (GSK3β) like kinase (LjSK190-467) has been resolved at 2.9 Å resolution, providing, for the first time, structural data for a plant GKS3β like kinase. The 3D structure of LjSK190-467 revealed conservation at the structural level for this plant member of the GSK3β family. However, comparative structural analysis to the human homologue revealed significant differences at the N- and C-termini, supporting the notion for an additional regulatory mechanism in plant GSK3-like kinases. Structural similarities at the catalytic site and the ATP binding site explained the similarity in the function of the human and plant protein. LjSK1 and lupeol are strongly linked to symbiotic bacterial infection and nodulation initiation. An inhibitory capacity of lupeol (IC50 = 0.77 μM) for LjSK1 was discovered, providing a biochemical explanation for the involvement of these two molecules in nodule formation, and constituted LjSK1 as a molecular target for the discovery of small molecule modulators for crop protection and development. Studies on the inhibitory capacity of two phytogenic triterpenoids (betulinic acid and hederacoside C) to LjSK1 provided their structure-activity relationship and showed that hederacoside C can be the starting point for such endeavors.

Electrochemical and structural characterization of recombinant respiratory proteins of the acidophilic iron oxidizer Ferrovum sp. PN-J47-F6 suggests adaptations to the acidic pH at protein level.

The tendency of the periplasmic redox proteins in acidophiles to have more positive redox potentials (Em) than their homologous counterparts in neutrophiles suggests an adaptation to acidic pH at protein level, since thermodynamics of electron transfer processes are also affected by acidic pH. Since this conclusion is mainly based on the electrochemical characterization of redox proteins from extreme acidophiles of the genus Acidithiobacillus, we aimed to characterize three recombinant redox proteins of the more moderate acidophile Ferrovum sp. PN-J47-F6. We applied protein film voltammetry and linear sweep voltammetry coupled to UV/Vis spectroscopy to characterize the redox behavior of HiPIP-41, CytC-18, and CytC-78, respectively. The Em-values of HiPIP-41 (571 ± 16 mV), CytC-18 (276 ± 8 mV, 416 ± 2 mV), and CytC-78 (308 ± 7 mV, 399 ± 7 mV) were indeed more positive than those of homologous redox proteins in neutrophiles. Moreover, our findings suggest that the adaptation of redox proteins with respect to their Em occurs more gradually in response to the pH, since there are also differences between moderate and more extreme acidophiles. In order to address structure function correlations in these redox proteins with respect to structural features affecting the Em, we conducted a comparative structural analysis of the Ferrovum-derived redox proteins and homologs of Acidithiobacillus spp. and neutrophilic proteobacteria. Hydrophobic contacts in the redox cofactor binding pockets resulting in a low solvent accessibility appear to be the major factor contributing to the more positive Em-values in acidophile-derived redox proteins. While additional cysteines in HiPIPs of acidophiles might increase the effective shielding of the [4Fe-4S]-cofactor, the tight shielding of the heme centers in acidophile-derived cytochromes is achieved by a drastic increase in hydrophobic contacts (A.f. Cyc41), and by a larger fraction of aromatic residues in the binding pockets (CytC-18, CytC-78).

A Comparative Analysis of G7 and BRICS Corporate Tax Structures and their Impact on Economic Growth: A Quantitative Study from 1990 to 2022

A Comparative Analysis of G7 and BRICS Corporate Tax Structures and their Impact on Economic Growth: A Quantitative Study from 1990 to 2022

Comparative structural analysis of samples of transpedicular screws from titanium alloys

The article presents studies of transpedicular screws made of titanium alloy BT6. A metallographic and microstructural analysis of screw blanks, prototypes of transpedicular screws made of BT6 alloy and commercially produced screws made of Ti-6Al-4V was performed. Specimens of transpedicular screws were manufactured using the vortex thread cutting method on a CITIZEN Cincom K16E-VII automatic lathe. The microgeometry of the screw surface was created by sandblasting using quartz sand as an abrasive material. Studies have shown that experimental and foreign samples of transpedicular screws have a similar microstructure, consisting of globular crystals of the β-phase located in a light matrix of the α-phase. The microhardness of the rod part of the screw made of Ti-6Al-4V alloy was 312...338 HV, the microhardness of the material of the prototypes was from 264 to 394 HV. Conclusions have been drawn that determine the feasibility of choosing rods made of titanium alloy BT6 as a blank for the manufacture of transpedicular screws.

Co-precipitation vs. Green Synthesis: A Comparative Analysis of Structure, Morphology, Optical Properties, and Antibacterial Activity of Ag/ZnO Nanocomposite

Ag/ZnO nanocomposites were successfully prepared through co-precipitation (CS) and a green synthesis (GS) route mediated by Moringa Oleifera. The confirmation of their formation was evident from the simultaneous presence of Ag and ZnO reflections in powder X-ray diffraction. Field emission scanning electron microscopy (FESEM) analysis disclosed an average particle size of approximately 22 nm and 146 nm for CS and GS samples, respectively. The CS sample exhibited a disstinctive flower-like morphology, indicating a unique self-assembly and growth pattern, while the GS sample displayed an almost rectangular shape. Structural composition and functional groups in the nanocomposites were analyzed using FT-IR spectroscopy. The direct band gaps were determined as 3.12 eV for CS and 3.10 eV for GS samples using a Tauc plot derived from UV-Vis NIR spectrometry. Notably, the antibacterial evaluation of the green-synthesized Ag/ZnO exhibited a pronounced zone of inhibition against both gram-positive (S. aureus) and gram-negative (E. coli) bacteria, demonstrating superior efficacy compared to chemically prepared Ag/ZnO. Overall, the study highlights the successful synthesis, structural characterization, and enhanced antibacterial properties of Ag/ZnO nanocomposites via a green route mediated by Moringa Oleifera. GRAPHICAL ABSTRACT

Comparative Analysis of the Volatility Structures of the Stock Prices of Energy Companies Traded on the Kazakhstan Stock Exchange and International Gold and Oil Prices

The return of its stock exchange and the companies traded within are one of the important indicators for a national economy. Due to the global structure of stock markets, returns are closely related to both national and international market variables. This study makes a comparative analysis of the volatility structures of the energy companies traded in the Kazakhstan Stock Exchange (KASE) and the combined stock market index and gold and oil prices in international markets for the period between January 01, 2021, and June 31, 2023. The research focused on two issues. The first is the analysis of the volatility structure of the six series examined. For this purpose, four different models were examined. The second focus is to determine whether the returns in international indices have a causal effect on the Kazakhstan stock market (composite stock market index) and the returns of oil and energy companies traded in the stock market. The results revealed that other indices and returns have a similar variable variance structure, except for the KASE. The relevant coefficient estimation was found to be significant in both conditional standard deviation models for the KASE index. The coefficient estimate of the GARCH-M(1,1) model in the OIL index was significant, whereas conditional standard deviation models and the relevant coefficients of both conditional standard deviation models were found to be statistically insignificant in the other returns. This is an indication of the structural compatibility of Kazakhstan's stock market composite index and energy and oil companies with international markets. Furthermore, the causality analysis results showing that international indices have a causal effect on KASE and KZAP is another indicator that the Kazakhstan market works in harmony with the international markets.

Brain connectivity for subtypes of parkinson's disease using structural MRI.

Objective. Delineating Parkinson's disease (PD) into distinct subtypes is a major challenge. Most studies use clinical symptoms to label PD subtypes while our work uses an imaging-based data-mining approach to subtype PD. Our study comprises two major objectives - firstly, subtyping Parkinson's patients based on grey matter information from structural magnetic resonance imaging scans of human brains; secondly, comparative structural brain connectivity analysis of PD subtypes derived from the former step.Approach. Source-based-morphometry decomposition was performed on 131 Parkinson's patients and 78 healthy controls from PPMI dataset, to derive at components (regions) with significance in disease and high effect size. The loading coefficients of significant components were thresholded for arriving at subtypes. Further, regional grey matter maps of subtype-specific subjects were separately parcellated and employed for construction of subtype-specific association matrices using Pearson correlation. These association matrices were binarized using sparsity threshold and leveraged for structural brain connectivity analysis using network metrics.Main results. Two distinct Parkinson's subtypes (namely A and B) were detected employing loadings of two components satisfying the selection criteria, and a third subtype (AB) was detected, common to these two components. Subtype A subjects were highly weighted in inferior, middle and superior frontal gyri while subtype B subjects in inferior, middle and superior temporal gyri. Network metrics analyses through permutation test revealed significant inter-subtype differences (p < 0.05) in clustering coefficient, local efficiency, participation coefficient and betweenness centrality. Moreover, hubs were obtained using betweenness centrality and mean network degree.Significance. MRI-based data-driven subtypes show frontal and temporal lobes playing a key role in PD. Graph theory-driven brain network analyses could untangle subtype-specific differences in structural brain connections showing differential network architecture. Replication of these initial results in other Parkinson's datasets may be explored in future. Clinical Relevance- Investigating structural brain connections in Parkinson's disease may provide subtype-specific treatment.

Diversity assessment of a lesser known buffalo population from Central India and its comparative evaluation reveals presence of sufficient genetic variation and absence of selection

Planned breeding and conservation strategies for a lesser-known population require an assessment of complete genetic diversity and population structure analysis in addition to its morphometric characteristics. In the present study, a comparative analysis of the genetic structure of a rare buffalo population, namely Chhattisgarhi, was extensively studied using a panel of FAO-recommended microsatellite markers along with well-established breeds namely Murrah, Nili-Ravi, Gojri, Kalahandi, and Nagpuri. Mode shift analysis indicated the absence of genetic bottleneck in the recent past. Assessment of genetic diversity indices across all loci indicated the presence of sufficient genetic variation within and between populations. Analysis of molecular variance between the six different buffalo populations attributed 19.05% of the variations to between-population differentiation. Cluster analyses using DAPC and Bayesian approach along with the phylogenetic tree based on UPGMA grouped six populations into three groups. The Chhattisgarhi population was revealed to be genetically closer to Nagpuri and Kalahandi populations. The study reveals the presence of sufficient genetic diversity within the Chhattisgarhi population and indicates the absence of a systematic selection program. We suggest improvement and conservation programs should be planned for this breed in the near future through short-term selection.

Fecal Microbiota and Feeding Habitats of Nomadic Indigenous Animals (Deer, Yak, Sheep and Camel) in Baikal Siberia (Russia)

In the vast expanse of Baikal Siberia, indigenous nomadic animal groups have been conserved, grazing on pastures throughout the year. It is believed that the fecal microbiota of these diverse nomadic animal species is unique to each species and closely tied to their feeding environments. We conducted a pioneering comparative analysis of the taxonomic structure and the diversity of fecal microbiota in indigenous nomadic animals inhabiting Baikal Siberia. Our study encompassed 20 deer, 23 yaks, 24 camels, and 29 sheep, using high-throughput 16S rRNA gene profiling. In the fecal microbiota of these animals, we observed a predominant presence of the phyla Bacillota, Bacteroidota, and Verrucomicrobiota, collectively comprising over 88% of the microbial communities. Moreover, these proportions exhibited variations according to the host species. The unculturable Bacillota UCG-005 and UCG-010 are the key groups for all animals. However, at the genus level, distinctive compositions of fecal microbiota were discernible within each animal group. We identified a total of 37 dominant genera across the fecal samples from these four animal species. Principal component analysis (PCA) and cluster analysis demonstrated that the fecal microbiota composition clustered among individuals of the same animal species. Linear discriminant analysis effect size (LEfSe) indicated that camels exhibited higher abundances of the family Akkermansiaceae and the uncultured clostridial lineage UCG-010, while deer featured Lachnospiraceae; sheep had Ruminococcaceae; and yaks displayed Monoglobaceae, Bacteroidaceae, and methanogenic archaea from the family Methanobacteriaceae as distinctive marker taxa. Our studies showed that the studied nomadic animals feed mainly on plants belonging to the families Poaceae, Cyperaceae, Asteraceae, and Rosaceae. Our research indicated that the identity of the host species and, to a lesser degree, their diets and habitats, significantly shape the composition of fecal microbiota in these studied nomadic ruminant animals.

Mutational analysis of SARS-CoV-2 ORF6-KPNA2 binding interface and identification of potent small molecule inhibitors to recuse the host immune system.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surfaced on 31 December, 2019, and was identified as the causative agent of the global COVID-19 pandemic, leading to a pneumonia-like disease. One of its accessory proteins, ORF6, has been found to play a critical role in immune evasion by interacting with KPNA2 to antagonize IFN signaling and production pathways, resulting in the inhibition of IRF3 and STAT1 nuclear translocation. Since various mutations have been observed in ORF6, therefore, a comparative binding, biophysical, and structural analysis was used to reveal how these mutations affect the virus's ability to evade the human immune system. Among the identified mutations, the V9F, V24A, W27L, and I33T, were found to have a highly destabilizing effect on the protein structure of ORF6. Additionally, the molecular docking analysis of wildtype and mutant ORF6 and KPNA2 revealed the docking score of - 53.72 kcal/mol for wildtype while, -267.90 kcal/mol, -258.41kcal/mol, -254.51 kcal/mol and -268.79 kcal/mol for V9F, V24A, W27L, and I33T respectively. As compared to the wildtype the V9F showed a stronger binding affinity with KPNA2 which is further verified by the binding free energy (-42.28 kcal/mol) calculation. Furthermore, to halt the binding interface of the ORF6-KPNA2 complex, we used a computational molecular search of potential natural products. A multi-step virtual screening of the African natural database identified the top 5 compounds with best docking scores of -6.40 kcal/mol, -6.10 kcal/mol, -6.09 kcal/mol, -6.06 kcal/mol, and -6.03 kcal/mol for tophit1-5 respectively. Subsequent all-atoms simulations of these top hits revealed consistent dynamics, indicating their stability and their potential to interact effectively with the interface residues. In conclusion, our study represents the first attempt to establish a foundation for understanding the heightened infectivity of new SARS-CoV-2 variants and provides a strong impetus for the development of novel drugs against them.

A conformational selection mechanism of flavivirus NS5 for species-specific STAT2 inhibition

Flaviviruses, including Zika virus (ZIKV) and Dengue virus (DENV), rely on their non-structural protein 5 (NS5) for both replication of viral genome and suppression of host IFN signaling. DENV and ZIKV NS5s were shown to facilitate proteosome-mediated protein degradation of human STAT2 (hSTAT2). However, how flavivirus NS5s have evolved for species-specific IFN-suppression remains unclear. Here we report structure-function characterization of the DENV serotype 2 (DENV2) NS5−hSTAT2 complex. The MTase and RdRP domains of DENV2 NS5 form an extended conformation to interact with the coiled-coil and N-terminal domains of hSTAT2, thereby promoting hSTAT2 degradation in cells. Disruption of the extended conformation of DENV2/ZIKV NS5, but not the alternative compact state, impaired their hSTAT2 binding. Our comparative structural analysis of flavivirus NS5s further reveals a conserved protein-interaction platform with subtle amino-acid variations likely underpinning diverse IFN-suppression mechanisms. Together, this study uncovers a conformational selection mechanism underlying species-specific hSTAT2 inhibition by flavivirus NS5.