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

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

• The paper examines a host-viral interactome of 1432 human proteins to pinpoint critical nodes influencing COVID-19 pathogenesis.
• It employs network centrality and functional enrichment analyses to map proteins involved in cellular signaling and respiratory pathways.
• The study highlights proteins like RBX1 and HSPA5 as promising therapeutic targets for combating COVID-19.

The paper "Analyzing Host-Viral Interactome of SARS-CoV-2 for Identifying Vulnerable Host Proteins during COVID-19 Pathogenesis" explores the intricate molecular mechanisms that underscored the infection process of SARS-CoV-2 during the COVID-19 pandemic. The primary focus lies in identifying key host proteins that could serve as potential therapeutic targets.

The authors synthesized a substantial dataset by consolidating existing protein-protein and gene interactions related to SARS-CoV-2. This integrative approach led to the construction of a comprehensive host protein-protein interaction network, encompassing 1432 human proteins. The goal was to leverage this network to pinpoint proteins central to the host's response to viral infection.

Key steps undertaken in the study include:

1. Network Centrality Measures: By calculating network centrality measures, the researchers identified critical proteins within the interactome. Centrality in network theory often correlates with the importance of nodes (in this case, proteins) in the overall connectivity and functionality of the network.
2. Functional Enrichment Analysis: Following the identification of central proteins, a functional enrichment analysis was performed. This step mapped the central proteins to biological pathways and processes, revealing their involvement in several essential cellular mechanisms. Specifically, these proteins were implicated in pathways related to cellular processes, signal transduction, and neurodegenerative diseases.
3. Targeting Respiratory Tract Diseases: Particular attention was given to proteins involved in diseases affecting the human respiratory tract, due to the respiratory nature of COVID-19. The paper suggests that SARS-CoV-2 infection triggers a multifaceted disease state, implicating various host proteins.

Lastly, the study identifies several proteins as potential therapeutic targets due to their centrality in the network and their association with multiple diseases. Among these, RBX1, HSPA5, ITCH, RAB7A, RAB5A, RAB8A, PSMC5, CAPZB, CANX, IGF2R, and HSPA1A stand out. These proteins are not only pivotal in the host's protein network but also intersect with pathways that could be manipulated for therapeutic benefit against COVID-19.

In conclusion, this paper underscores the complexity of COVID-19 pathogenesis and illuminates several potential targets for future therapeutic interventions. The integration of global research efforts in understanding the host-viral interactome paved the way for identifying these critical proteins, which act as potential nodes for intervention in combating the disease.