Interactome of Human and SARS-CoV-2 Proteins to Identify
Human Hub Proteins Associated with Comorbidities

Nimisha Ghosh^1,2,+, Indrajit Saha^3,+,*, Nikhil Sharma⁴,

¹Department of Computer Science and Information Technology, Institute of Technical Education and Research,
Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, India
²Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, Warsaw, Poland
³Department of Computer Science and Engineering, National Institute of Technical Teachers' Training and Research, Kolkata, India
⁴Department of Electronics and Communication Engineering, Jaypee Institute of Information Technology, Noida, India
*Correspondence should be addressed to team leader : indrajit@nitttrkol.ac.in
⁺These team members contributed equally to this work

ABSTRACT

SARS-CoV-2 has a higher chance of progression in adults of any age with certain underlying health conditions or comorbidities like cancer, neurological diseases and in certain cases may even lead to death. Similar to other viruses, SARS-CoV-2 also interacts with host proteins to pave its entry into host cells. Therefore, to understand the behaviour of SARS-CoV-2 and design of effective antiviral drugs, host-virus protein-protein interactions (PPIs) can be very useful. In this regard, we have initially created a human-SARS-CoV-2 PPI database based on literature survey which has resulted in 7085 unique PPIs. Subsequently, we have identified at most 10 proteins with highest degrees viz. hub proteins from interacting human proteins for individual virus protein. The identification of these hub proteins are important as they are connected to most of the other human proteins and when they get affected, the potential illnesses in the corresponding pathways get aggravated leading to comorbidities. Furthermore, the biological significance of the identified hub proteins is shown using KEGG pathway and GO enrichment analysis. KEGG pathway analysis is also essential for identifying the pathways leading to comorbidities. Among others, SARS-CoV-2 proteins viz. NSP2, NSP5, Envelope and ORF10 interacting with human hub proteins like COX4I1, COX5A, COX5B, NDUFS1, CANX, HSP90AA1 and TP53 lead to comorbidities. Such comorbidities are Alzheimer, Parkinson, Huntington, HTLV-1 infection, prostate cancer and viral carcinogenesis. Subsequently, possible repurposable drugs targeting the human hub proteins are reported in this paper as well using Enrichr tool. This work thus provides a consolidated study for human-SARS-CoV-2 protein interactions to understand the relationship between comorbidity and hub proteins so that it may pave the way for the development of anti-viral drugs.