Identifying the interactome of altered ion channels with lipid metabolism in SARS-CoV-2 infected patients in post-COVID-19 era

Abstract

The Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection continues to expand its horizon through the development of diverse symptoms, particularly concerning long COVID. The patients infected with the SARS-CoV-2 are being reported to develop new symptoms such as brain fog, fatigue, and other symptoms that are not limited to the respiratory system. The SARS-CoV-2 utilizes the human ion channels (HICs) and molecules involved in lipid metabolism from their entry to their egress. Here, to identify molecular alterations in HICs and lipid metabolism-related genes, transcriptomic data of 277 SARS-CoV-2 infected patients were analyzed. 287 HICs and 754 lipid metabolism-related genes were found to be differentially expressed in SARS-CoV-2 infected patients. Further, an interactome of altered HICs and lipid metabolism-related proteins with SARS-CoV-2 proteins was generated. Extensive data mining approach was employed to generate a pathway map highlighting alteration in several pathways including calcium signaling, long-term depression, and cholesterol metabolism in SARS-CoV-2 infected patients. Moreover, 17 potential drugs with known modes of action that interact with 4 altered HICs including inositol 1,4,5-triphosphate (InsP3) receptors and gap junction protein alpha 1 were identified. Most likely, these HICs are potential candidates for drug repurposing in patients infected with SARS-CoV-2 and require further experimental validation.