Comparative structural analysis of host proteins involved in SARS-CoV-2 infection

Covid-19 is a global pandemic that has led to approximately five million deaths. Extensive research studies, especially in bioinformatics, are being conducted to study SARS-CoV-2, its spike proteins and associated host proteins. These studies are particularly critical for drug discovery and repurposing. Angiotensin-converting enzyme 2(ACE2) receptor plays a significant role in SARS-CoV-2 pathogenesis, while transmembrane protease serine 2 (TMPRSS2) and Furin proteins promote viral entry into host cells. Using 3D structure data from the SCOP and PDB databases, we conducted structural alignments of the three key human proteins involved in SARS-CoV-2 infection: ACE2, TMPRSS2, and Furin. These were compared with all 3D protein structures available in databases, using various structural alignment algorithms. The resulting data were merged into an assembled dataset. Conserved binding pockets among structurally similar proteins were identified. The highest protein similarity to ACE2 was found using the TM-align algorithm, which identified as 2O36:A protein chain (Thimet oligopeptidase, classified as proteolysis protein). For TMPRSS2, the highest similarities were found using algorithms from the Topology-Independent category and identified as the highest similarity (0.94) was 3W94:A protein chain, named Enteropeptidase-1. While the highest similarity to Furin was found using the TM-align algorithm, which identified as 1OT5:A protein chain (Kexin, classified as Hydrolase/ Hydrolase Inhibitor protein). The structural insights provided by this study offer critical pathways for repurposing drugs and designing inhibitors targeting ACE2, TMPRSS2, and Furin, potentially aiding the fight against COVID-19 and other viral infections. Structural similarities in viral proteins reveal new drug targets to combat SARS-CoV-2 infection. Conserved protein sites offer insights into broad-spectrum antiviral treatments against coronaviruses. Drug repurposing opportunities emerge by mapping protein structures shared across viruses and hosts.