Biotechnology Industry Research Assistance Council

Tropical and sub‐tropical regions mostly provide favorable conditions for the spread of vector‐borne diseases especially those transmitted by mosquito vectors. Viral disease outbreaks such as dengue, chikungunya, Japanese encephalitis; and parasitic diseases such as malaria, and filariasis; are common health problems caused by mosquitos. According to the World Health Organization (WHO), globally around 40% of people are at high risk of mosquito‐borne diseases (MBD) (WHO Fact‐sheets, 2020, https://www.who.int/news‐room/fact‐sheets/detail/vector‐borne‐diseases). In the present study, Remote Sensing methods integrated with Geographic Information System (GIS) have been used to predict the risk zones for MBD in Cuttack, a district of Odisha, the eastern state of India. The findings of this study could be utilized to develop and implement MBD control and prevention strategies in identified high‐risk areas. Under this study, the Landsat‐8 multispectral temporal images from 2018 to 2021 were used to identify and demarcate the water‐logged areas and sites favorable for mosquito breeding. The goal is to identify risk zones for MBD using different indices such as Normalized Difference Water Index, Normalized Difference Moisture Index, Normalized Difference Vegetation Index, and Land Surface Temperature by evaluating water, moisture, vegetation, and temperature parameters. Applying Arc GIS software analysis models,we found 11,730.07 Ha. as a high‐risk zone, 28,053.99 Ha. as a medium‐risk zone, and 12,669.69 Ha. as a low‐risk zone. This study has the potential to enable informed decision‐making and proactive mosquito‐borne disease prevention.

ABSTRACT Mcl-1, a Bcl-2 family protein, is a key regulator of apoptosis and is often overexpressed in cancers such as lung, breast, pancreatic, cervical, ovarian cancers, leukemia, and lymphoma. Its role in inhibiting apoptosis enables tumor cells to evade cell death and contributes to drug resistance. Targeting Mcl-1 is crucial in inducing apoptosis and overcoming resistance to therapies that target other anti-apoptotic proteins, making it a prominent target for anticancer drug development across multiple malignancies. So, our study aimed to discover potent antileukemic compounds targeting MCL1. We began by selecting a diverse set of molecules from the BindingDB database to construct a structure-based pharmacophore model, which was subsequently used to virtually screen a library of 407,270 compounds from the COCONUT database. Subsequently, we developed an e-pharmacophore model using the co- crystallized inhibitor AMG-176, for further screening. A QSAR model was then implemented to estimate the IC 50 values of these compounds, filtering those with predicted IC 50 values below the median. The top hits were subjected to molecular docking and MMGBSA binding energy calculations against MCL1, leading to the selection of two promising candidates for further ADMET analysis. To assess their electronic properties, density functional theory (DFT) calculations were conducted, which included geometry optimization, frontier molecular orbital (FMO) analysis, HOMO-LUMO gaps, and global reactivity descriptors. These analyses confirmed favourable profiles and reactivity for the chosen compounds. In addition, predictions for physicochemical and ADMET properties aligned well with the expected bioactivity and safety profiles of the candidates. Molecular dynamics (MD) simulations further validated their strong binding affinity and stability, positioning them as potential MCL1 inhibitors. Our comprehensive computational approach highlights these compounds as promising and safe antileukemic agents, with future in vivo and in vitro validation recommended for further confirmation.

Background: Mutations in isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are prevalent drivers of acute myeloid leukemia (AML). While targeted therapies exist, resistance can emerge. This study explored the potential of natural products to identify novel dual IDH inhibitors. Methods: In-silico screening of the COCONUT database was performed using Lipinski's Rule of Five. Pharmacophore modelling identified crucial features for IDH binding. Docking simulations with Glide (Schrodinger) assessed binding affinity, followed by MM-GBSA calculations for free energy estimation. The most promising candidate underwent ADME/T and toxicity analysis. Finally, molecular dynamics (MD) simulations evaluated the stability of protein-ligand complexes and binding interactions, followed by trajectory analysis using DCCM and PCA. Results: The study identified Ternstroside D (CNP0166496) as a potential dual inhibitor for IDH1 and IDH2 mutations. Docking simulations and MM-GBSA calculations predicted favourable binding affinities. MD simulations revealed stable protein-ligand complexes, and in-silico ADME/T analysis suggested good drug-like properties and a favorable safety profile for CNP0166496. Conclusion: This in-silico study provides compelling evidence for Ternstroside D (CNP0166496) as a promising dual inhibitor for IDH1 and IDH2 mutations in AML. Further in-vitro and in-vivo studies are warranted to validate these findings.

IntroductionColorectal cancers are the world’s third most commonly diagnosed type of cancer. Currently, there are several diagnostic and treatment options to combat it. However, a delay in detection of the disease is life-threatening. Additionally, a thorough analysis of the exomes of cancers reveals potential variation data that can be used for early disease prognosis.MethodsBy utilizing a comprehensive computational investigation, the present study aimed to reveal mutations that could potentially predispose to colorectal cancer. Ten colorectal cancer exomes were retrieved. Quality control assessments were performed using FastQC and MultiQC, gapped alignment to the human reference genome (hg19) using Bowtie2 and calling the germline variants using Haplotype caller in the GATK pipeline. The variants were filtered and annotated using SIFT and PolyPhen2 successfully categorized the mutations into synonymous, non-synonymous, start loss and stop gain mutations as well as marked them as possibly damaging, probably damaging and benign. This mutational profile helped in shortlisting frequently occurring mutations and associated genes, for which the downstream multi-dimensional expression analyses were carried out.ResultsOur work involved prioritizing the non-synonymous, deleterious SNPs since these polymorphisms bring about a functional alteration to the phenotype. The top variations associated with their genes with the highest frequency of occurrence included LGALS8, CTSB, RAD17, CPNE1, OPRM1, SEMA4D, MUC4, PDE4DIP, ELN and ADRA1A. An in-depth multi-dimensional downstream analysis of all these genes in terms of gene expression profiling and analysis and differential gene expression with regard to various cancer types revealed CTSB and CPNE1 as highly expressed and overregulated genes in colorectal cancer.ConclusionOur work provides insights into the various alterations that might possibly lead to colorectal cancer and suggests the possibility of utilizing the most important genes identified for wet-lab experimentation.

Microalgae have been widely used in industrial applications around the world for centuries, but large-scale cultivation of algae in photobioreactor (PBR) is still facing many challenges in terms of cost of construction, system size, culture sustainability, and productivity. The production of algal feedstock is hindered by the inability to translate laboratory studies into field scaleups. This chapter focuses on the research conducted for the construction of a low-cost flat panel PBR system and optimisation of its operational strategies. The microalgal strain chosen for mass cultivation is the indigenous halophilic species, Pseudanabaena limnetica (Lemm.) Komárek, which can withstand high temperature and high light intensity in summer season and can be grown in seawater. Therefore, real seawater has been used in this research study of cost-effective biomass production. Three scales of airlift panels have been developed for the flat panel PBR system, ranging from 8L up to 250L. The dimensions of the airlift panels are as follows: 1st : 25 cm x 38 cm x 10 cm (8L), 2nd : 50 cm x 70 cm x 20 cm (60L), 3rd : 100 cm x 110 cm x 28 cm (250L). A study was conducted to optimize the air flow rate and the size of the sparger pore for adequate aeration (CO2) and agitation. Physical parameters like, Sparger velocity (v) m/s along with change in Reynolds number (Re), superficial velocity of gas (Usg), gas holdup (\(\varepsilon\)) was studied for their efficiency to support algal growth. Also, optimization of other important parameters like light intensity, inoculum size was carried out in laboratory condition and correlated with the biomass production. Each PBR was operated outdoors after optimization. Electric power consumption was also discussed along with its cost estimation and total biomass productivity as well as the operational feasibility of the PBR systems developed. After optimizing the operational strategy for the working of PBRs in lab and outdoor conditions, it was found that 60L flat panel was the most suitable for large-scale cultivation of P. limnetica. Therefore, attempts have been made to construct and assemble 1000L PBR using 60L PBR units in outdoor conditions.

Studies have shown that transcription factor AP2A2 (activator protein-2 alpha-2) is involved in the expression of DLEC1, a tumor suppressor gene, which, when mutated, will cause breast cancer and is thus an excellent target for breast cancer studies. Therefore, in the present research, a synergistic approach toward combating breast cancer is proposed by blocking AP2A2 factor, and allowing the cancer cells to be sensitive to anti-cancer drugs. The effect of AP2A2 on breast cancer was first understood via gene analysis from cBioPortal. AP2A2 was then modeled using RaptorX and its structure was validated from Ramachandran plots. Using all ligands from MolPort database, molecular docking was performed against AP2A2, from which the top three best docked ligands were studied for toxicity in humans using Protox-II. Once the ligands passed these tests, the best complexes were simulated at 200ns in Desmond Maestro, to comprehend their stabilities, followed by the computations of free energies of binding via Molecular mechanics- Generalized Born Solvent Accessibility method (MM-GBSA). The results showed that molecules MolPort-005-945-556 (sachharolipids), MolPort-001-741-124 (flavonoids), and MolPort-005-944-667 (lignan glycosides) with AP2A2 passed toxicity evaluation and belonged to toxicity classes 6, 5, and 5, respectively, with good docking energies. 200ns simulations revealed stable complexes with slight conformational changes. Stability of ligands was confirmed via snapshots at every 20ns of the trajectory. Radial distribution of these molecules against the protein revealed very slight deviation from binding pocket. Additionally, the free binding energies for these complexes were found to be -54.93 ± 12.982kcal/mol, -44.39 ± 14.393kcal/mol, and -66.51 ± 13.522kcal/mol, respectively. A preliminary computational validation of the inability of AP2A2 to bind to DLEC1 in the presence of ligands offers beneficial insights into the potential of these ligands. Therefore, this study sheds light on the potential natural molecules that could stably block AP2A2 with least deviation and act in synergy to aid anti-cancer drugs work on breast cancer cells.

ABSTRACT Introduction Clubfoot, mainly CTEV, is a complex three-dimensional deformity challenging physicians from ancient times. Among a thousand babies born, one to six suffer from clubfoot deformity; that is, in India alone, around 35,000 need treatment for clubfoot annually. This review summarizes the various practices of clubfoot assessment, noninvasive treatment, and engineering aspects of clubfoot treatment. The shortcomings of assessment methods and challenges with implementation of treatment methods are also presented. Methods A narrative review of all related research papers available to authors was carried out. Results Various clubfoot assessment methods have been developed to help physicians understand the severity of the problem and predict treatment parameters. The Pirani score and Dimeglio score are used predominantly for the assessment of deformity. However, these methods suffer from implementation-related limitations. Noninvasive methods, namely, Kite's method, functional physiotherapy method, and Ponseti method, are used in practice for treatment. The Ponseti method is the most popular with parents and physicians and is considered the gold standard for the treatment of clubfoot. However, it also suffers from various implementation issues, like treatment cost and lack of experts, particularly in low- and middle-income countries (LMICs). Engineers are using various technologies like computer-aided design (CAD)/computer-aided engineering (CAE) and additive manufacturing for modeling and analysis of clubfoot. Engineers have also attempted to develop corrective and maintenance orthosis for CTEV treatment. Conclusions Because newer and newer technologies are becoming accessible for interdisciplinary use, there is a need to apply contemporary technologies, especially to develop a corrective orthosis so that the current challenges of clubfoot assessment and treatment are addressed. The corrective orthosis should be based on Dr Ponseti's insights into clubfoot biomechanics. Clinical Relevance There is a need to explore contemporary technologies like data acquisition and CAD/CAE to address CTEV assessment–related issues. A corrective orthosis based on the understanding of the foot biomechanics for treatment can solve the various implementation-related challenges of the Ponseti method, particularly in low-resource settings.

The present study was conducted to detect foot-and-mouth disease virus type ‘O’ in milk samples of FMD infected cattle and also to distinguish naturally infected from vaccinated cattle by use of DIVA ELISA. A total of 30 milk samples were collected from FMD infected cattle to carry out the study and serum samples were also collected from the same herd of animals. RNA extraction was done by Trizol method from milk samples. All the milk samples were found to be positive by RT-PCR for presence of Foot and mouth disease virus type O. Detection of antibody against non-strucructural protein using r3AB3 kit showed 100% positivity rate, which indicates the animals were naturally infected by Foot and mouth disease virus type O.