Mucormycosis Metabolic Network Modeling: A Constraint-Based Approach

Mucormycosis is an uncommon illness caused by the fungus Mucorales. India was concerned about mucormycosis and COVID-19 in 2020. To minimize morbidity and occurrence, prevent, and treat mucormycosis, analysis is required. Combining systems biology and bioinformatics-based mucormycosis research, this study simulates the Genome-scale metabolic model (GSSM) of a Rhizopus oryzae strain for the comprehension of the organism's metabolic mechanism. Several key metabolic pathways for a mucormycosis-causing fungus strain were identified in research publications and targeted for inclusion in a model of a metabolic network. Based on the Flux Balance Analysis (FBA) approach, an integrated model of these pathways at the scale of the genome's metabolism was developed and appropriate constraints were applied to the numerous reactions involved in Rhizopus oryzae's metabolism using the COBRA package in MATLAB. Hence, unique evidence of pharmacological targets and biomarkers that may function as diagnostic, early analytic, and therapeutic agents in mucormycosis was discovered. Our study investigates the role of key metabolites in the model by applying constraints and altering fluxes, which provides valuable candidates for drug development. . © 2023 IEEE.

In-Silico Structure-Based Drug Discovery of Candidate Drugs Against Novel Protein Receptor Complex Nsp10-Nsp16 of SARS-CoV-2 Using Drug Repurposing Approach

Background: Several therapeutic possibilities have been explored against Severe Acute Respiratory Syndrome-2 (SARS-CoV-2), such as convalescent plasma (CP), intravenous immunoglobulin (IVIG) and monoclonal antibodies. Compounds such as hydroxychloroquine have also been found to have fatal drawbacks. Repurposing of existing antiviral drugs can be an effective strategy, which could fasten up the process of drug discovery. Objective(s): The present study is designed to predict the computational efficacy of pre-existing antiviral drugs as inhibitors for the Nsp10-Nsp16 complex protein of SARS-CoV-2. Method(s): Twenty-six known antiviral drugs along with their similar structures based on Tanimoto simi-larity, were screened towards the Nsp10-Nsp16 complex's active site. Result(s): Our study reports competitive binding of 1-[3-[2-(2-Ethoxyphenoxy) ethylamino]-2-hydroxypropyl]-9H-carbazol-4-ol against AdoMet binding site in Nsp10-Nsp16 complex. Formation of the stable ligand-receptor complex with 1-[3-[2-(2-Ethoxyphenoxy) ethylamino]-2-hydroxypropyl]-9H-carbazol-4-ol could functionally inhibit the Nsp10-Nsp16 complex, thereby making the SARS-CoV-2 vulnerable to host immuno-surveillance mechanisms. Conclusion(s): We conclude that these computational hits can display positive results in in-vitro trials against SARS-CoV-2.Copyright © 2021 Bentham Science Publishers.