Phytomolecules as potential candidates to intervene the function of E. coli sodium-proton antiporters; Ec-NhaA.

Sodium-Proton antiporter, NhaA is a ubiquitous protein found in cytoplasmic membranes of all the prokaryotic and eukaryotic systems. These antiporters have been widely studied in E. coli and their homologs, observed in humans, are found to be crucial for various pathophysiological conditions, such as hypertension, cardiac diseases, blood pressure fluctuation etc. NhaA is responsible for the virulent properties of many pathogens like Vibrio cholerae, Yersinia pestis etc. In the present work, we have exploited in silico approaches to find lead phytomolecules that have the efficacy to interfere with the activities of sodium-proton antiporters in E. coli. A database of the plant-based natural bioactive compounds was used to screen 350 phytochemicals from various plant sources as potential ligands for the Ec-NhaA protein (PDB ID: 4ATV). Further interactions between Ec-NhaA and ligands were analyzed by AutoDock Vina and proposed 46 ligands with a significant affinity for NhaA where the binding energy range from -7.5 to -9.3 kcal/mol. Physiochemical characterization suggested 26 ligands with non-BBB permeability, good GI absorption and solubility. As a final step, MD simulation for more than 100 ns duration suggested Luteolin, Apigenin and Rhamnocitrin with the best affinity and showing potential stable interaction with the target protein. This study proposed the potential compounds of natural origin as an interfering agent against sodium-proton transport activity that may lead to affect the survival of various pathogenic bacteria.Communicated by Ramaswamy H. Sarma.

Missense mutations in spike protein of SARS-CoV-2 delta variant contribute to the alteration in viral structure and interaction with hACE2 receptor.

INTRODUCTION: Many of the global pandemics threaten human existence over the decades among which coronavirus disease (COVID-19) is the newest exposure circulating worldwide. The RNA encoded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is referred as the pivotal agent of this deadly disease that induces respiratory tract infection by interacting host ACE2 receptor with its spike glycoprotein. Rapidly evolving nature of this virus modified into new variants helps in perpetrating immune escape and protection against host defense mechanism. Consequently, a new isolate, delta variant originated from India is spreading perilously at a higher infection rate. METHODS: In this study, we focused to understand the conformational and functional significance of the missense mutations found in the spike glycoprotein of SARS-CoV-2 delta variant performing different computational analysis. RESULTS: From physiochemical analysis, we found that the acidic isoelectric point of the virus elevated to basic pH level due to the mutations. The targeted mutations were also found to change the interactive bonding pattern and conformational stability analyzed by the molecular dynamic's simulation. The molecular docking study also revealed that L452R and T478K mutations found in the RBD domain of delta variant spike protein contributed to alter interaction with the host ACE2 receptor. CONCLUSIONS: Overall, this study provided insightful evidence to understand the morphological and attributive impact of the mutations on SARS-CoV-2 delta variant.