In-silico binding affinity of a phage display library screened novel peptide against various FABPs.

In accordance to the American Heart Association (AHA), cardiovascular diseases (CVDs) are the leading cause of death around the globe, causing more than 19.1 million deaths in 2020. Heart-type fatty acid binding protein (H-FABP) is required for the metabolism of fatty acids (FA) inside cardiomyocytes is reported as a biomarker for myocardial damage. As early as one hour after an Acute myocardial infarction (AMI), H-FABP can be used to detect myocardial ischemia. Thus, H-FABP based detection can reduce the burden on the emergency department. A peptide-based detection system can provide point-of-care diagnostics for CVDs. There is a lot of research being done on peptide-based detection, and it has a lot of potential to help with unmet medical diagnostic needs. A twelve (12) amino acid peptide has been discovered using Phage Display Library Screening. The affinity of peptide with H-FABP and other FABPs has been done using molecular docking and ADMET profile has been done. Molecular docking of small peptides against the target protein can play a crucial role in recognizing peptide binding sites and poses. The docking study was done using the HDOCK server and the visualization of the docked complex was done using Pymol and UCSF chimera. The molecular simulation study of three protein-peptide complexes were done which also validated the binding affinity of peptide with the proteins. The RMSD, RMSF and radius of gyration are also analyzed. The results indicate that H-FABP shows higher level of binding interaction with the peptide having bond length ranging from 2.3 to 3.4 Å. The screened peptide is suitable for H-FABP binding and can be used for prognosis purposes in the heart ischemic conditions.

Repurposing FDA-approved compounds to target JAK2 for colon cancer treatment.

Colorectal cancer is one of the common cancers worldwide and the second leading cause of cancer-related death. The current treatment has the inherent drawbacks and there is a need of developing a new treatment. Interleukin-6 a pleiotropic cytokine involved in immune regulation and activation of JAK2/STAT3 pathway in colorectal cancer. JAK2/STAT3 signaling pathway functions as a critical regulator of cell growth, differentiation, and immune expression. The abnormality in the JAK2/STAT3 pathway is involved in the tumorigenesis of colon cancer including apoptosis. In this study, we identified novel inhibitors for JAK2 protein by performing virtual screening against FDA-approved compounds. To address the selectivity issue, we implemented cross-docking method followed by DFT calculations to understand the chemical reactivity of the identified compounds. Additionally, molecular dynamics (MD) simulations were performed for the top FDA compounds against JAK2 to understand the molecular interactions and structural stability of the complex over a period of 200 ns. Our results indicated that ergotamine, entrectinib, exatecan, dihydroergotamine, and paritaprevir can be used as alternative drugs for colon cancer. In addition, ergotamine was found to efficiently lower the cell viability with IC50 values of 100 µM on colon cancer cell lines. The long-term inhibitory effect of the ergotamine led to a decrease in colony size, and the toxicity properties were studied using hemolysis assay. Our study shows the potential of targeting JAK2 as a novel approach to colon cancer treatment, and demonstrate that ergotamine as a promising effects as an anti-cancer drug.

Characterization of Phytochemicals in Ulva intestinalis L. and Their Action Against SARS-CoV-2 Spike Glycoprotein Receptor-Binding Domain.

Coronavirus disease-2019 (COVID-19) has caused a severe impact on almost all aspects of human life and economic development. Numerous studies are being conducted to find novel therapeutic strategies to overcome COVID-19 pandemic in a much effective way. Ulva intestinalis L. (Ui), a marine microalga, known for its antiviral property, was considered for this study to determine the antiviral efficacy against severe acute respiratory syndrome-associated Coronavirus-2 (SARS-CoV-2). The algal sample was dried and subjected to ethanolic extraction, followed by purification and analysis using gas chromatography-coupled mass spectrometry (GC-MS). Forty-three known compounds were identified and docked against the S1 receptor binding domain (RBD) of the spike (S) glycoprotein. The compounds that exhibited high binding affinity to the RBD of S1 protein were further analyzed for their chemical behaviour using conceptual density-functional theory (C-DFT). Finally, pharmacokinetic properties and drug-likeliness studies were carried out to test if the compounds qualified as potential leads. The results indicated that mainly phenols, polyenes, phytosteroids, and aliphatic compounds from the extract, such as 2,4-di-tert-butylphenol (2,4-DtBP), doconexent, 4,8,13-duvatriene-1,3-diol (DTD), retinoyl-ß-glucuronide 6',3'-lactone (RBGUL), and retinal, showed better binding affinity to the target. Pharmacokinetic validation narrowed the list to 2,4-DtBP, retinal and RBGUL as the possible antiviral candidates that could inhibit the viral spike protein effectively.