Analyzing Host-Viral Interactome of SARS-CoV-2 for Identifying Vulnerable Host Proteins during COVID-19 Pathogenesis

TL;DR

This study constructs a comprehensive human protein interaction network related to SARS-CoV-2, identifying key proteins and pathways involved in COVID-19 pathogenesis to suggest potential therapeutic targets.

Contribution

It integrates diverse protein and genetic interaction data to identify central host proteins and pathways involved in COVID-19, highlighting potential therapeutic targets.

Findings

Identified 1432 human proteins involved in SARS-CoV-2 interactions.

Highlighted key proteins like RBX1, HSPA5, and RAB7A as potential therapeutic targets.

Associated identified proteins with crucial pathways such as cellular processes and neurodegenerative diseases.

Abstract

The development of therapeutic targets for COVID-19 treatment is based on the understanding of the molecular mechanism of pathogenesis. The identification of genes and proteins involved in the infection mechanism is the key to shed out light into the complex molecular mechanisms. The combined effort of many laboratories distributed throughout the world has produced the accumulation of both protein and genetic interactions. In this work we integrate these available results and we obtain an host protein-protein interaction network composed by 1432 human proteins. We calculate network centrality measures to identify key proteins. Then we perform functional enrichment of central proteins. We observed that the identified proteins are mostly associated with several crucial pathways, including cellular process, signalling transduction, neurodegenerative disease. Finally, we focused on proteins involved in causing disease in the human respiratory tract. We conclude that COVID19 is a complex disease, and we highlighted many potential therapeutic targets including RBX1, HSPA5, ITCH, RAB7A, RAB5A, RAB8A, PSMC5, CAPZB, CANX, IGF2R, HSPA1A, which are central and also associated with multiple diseases