RNA-Seq Analysis of Regulatory Mechanism of COVID-19 Patients for Elucidating Therapeutics

Abstract

A new coronavirus that has spread quickly around the world is what is causing the Coronavirus Disease 2019 (COVID-19) pandemic., inflicting a significant threat to human health by inflicting a wide variety of health complications, including multiple organ failure. This is the fifth coronavirus that causes severe damage to the human body, including damage to other organs like the heart, kidney, liver, and brain. It has an effect all over the body and leads to death. Currently, only symptomatic treatments, including drugs, are given to treat a secondary bacterial infection. In some cases, these drugs become resistant. Vaccines, which are designed for a specific variant of the virus, are available to deal with this infection while further necessary treatments are also required. The purpose of this study was to find a therapeutic target as well as to find the regulatory mechanism that leads to multiple organ failure. First, NGS analysis was performed to find differentially expressed genes on two data sets taken from the NCBI website. Common therapeutic targets were identified by performing comparative analysis on the differentially expressed genes of all the data sets. Pathway analysis was performed using Reactome on the common DEGs to identify targetable pathways. Based on pathway analysis, fourteen genes, including TNFRSF1A, FCER1G, CSF1, ICAM1, SRC, RHOA, CD40LG, LAT, LCN2, CXCL10, 1RF7, B2M, CD40, CTSL, were found to be involved in cytokine storm in different organs. Among these genes is Cathepsin L, which is a lysosomal cysteine protease. The fundamental function of cysteine cathepsins is the proteolysis of protein antigens produced by pathogen endocytosis, and they are expressed in all organs and cell types. During SARS-CoV2 infection, it helps in the cleavage of the S1 subunit of spike glycoprotein present on the surface of coronavirus. This cleavage is important for virus entry into host cells and viral replication. The Cathepsin L protein was used as a therapeutic target and the structure was modelled using the SWISS Model. Protein active sites were determined by DoGSiteScorer. Twenty-four ligands, which were inhibitors of Cathepsin L, were taken from PubChem and chEMBL to dock with the protein. For docking purposes, the AutoDock Vina was used. Cathepsin L demonstrated the highest binding affinity of -7.00 kcal/mol to a compound with the molecular formula C41H49N7O4S. List of Figures The Protein-Ligand Interaction Profiler (PLIP), an online tool, was used to study the interactions between protein and ligand and how these ligands interact with the protein.