Integration of System Biology Tools to Investigate Huperzine A as an Anti-Alzheimer Agent

Aim: The present study aimed to investigate huperzine A as an anti-Alzheimer agent based on the principle that a single compound can regulate multiple proteins and associated pathways, using system biology tools.Methodology: The simplified molecular-input line-entry system of huperzine A was retrieved from the PubChem database, and its targets were predicted using SwissTargetPrediction. These targets were matched with the proteins deposited in DisGeNET for Alzheimer disease and enriched in STRING to identify the probably regulated pathways, cellular components, biological processes, and molecular function. Furthermore, huperzine A was docked against acetylcholinesterase using AutoDock Vina, and simulations were performed with the Gromacs package to take into account the dynamics of the system and its effect on the stability and function of the ligands.Results: A total of 100 targets were predicted to be targeted by huperzine A, of which 42 were regulated at a minimum probability of 0.05. Similarly, 101 Kyoto Encyclopedia of Genes and Genomes pathways were triggered, in which neuroactive ligand–receptor interactions scored the least false discovery rate. Also, huperzine A was predicted to modulate 54 cellular components, 120 molecular functions, and 873 biological processes. Furthermore, huperzine A possessed a binding affinity of −8.7 kcal/mol with AChE and interacted within the active site of AChE via H-bonds and hydrophobic interactions.

A System Biology Approach to Explore Host-Pathogen Interaction Under Phytochemical Cross Linkages

Phyto-signalling molecules are minute, but tangible that has rigorous roles in any plant-pathogen interaction. Certainly, most of the pathogen alters their biosynthesis, transport, degradation and cellular signalling responses to pave their virulence. Therefore, the gene expressions of such molecules with their correlated defense mechanisms were analysed in Arabidopsis thaliana against Erysiphe orontii (a potential biotroph), Botrytis cinerea (a potential necrotroph), Pseudomonas syringae (a bacterial hemibiotroph), and Phytophthora infestans (a fungal hemibiotroph) using molecular biology/ system biology techniques. The findings strongly suggested that each pathogen has its own unique infection strategy based on up-regulation and down-regulation of host phyto-signalling genes. Our studies also explored four basic pathogenic infection maps based on cross linking phyto-signalling molecules.

Tryptophan-Kynurenine Pathway in COVID-19-Dependent Musculoskeletal Pathology: A Minireview

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), affecting multiple organ systems, including the respiratory tract and lungs. Several studies have reported that the tryptophan-kynurenine pathway is altered in COVID-19 patients. The tryptophan-kynurenine pathway plays a vital role in regulating inflammation, metabolism, immune responses, and musculoskeletal system biology. In this minireview, we surmise the effects of the kynurenine pathway in COVID-19 patients and how this pathway might impact muscle and bone biology.

A system biology approach identifies candidate drugs to reduce mortality in severely ill COVID-19 patients

Despite the availability of highly efficacious vaccines, Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) lacks effective drug treatment which results in a high rate of mortality. To address this therapeutic shortcoming, we applied a system biology approach to the study of patients hospitalized with severe COVID. We show that, at the time of hospital admission, patients who were equivalent on the clinical ordinal scale displayed significant differential monocyte epigenetic and transcriptomic attributes between those who would survive and those who would succumb to COVID-19. We identified mRNA metabolism, RNA splicing, and interferon signaling pathways as key host responses overactivated by patients who would not survive. Those pathways are prime drug targets to reduce mortality of critically ill COVID-19 patients leading us to identify Tacrolimus, Zotatifin, and Nintedanib as three strong candidates for treatment of severely ill patients at the time of hospital admission.