This study identifies 332 high-confidence host-pathogen protein-protein interactions (PPIs) between SARS-CoV-2 and human proteins, focusing on prey proteins involved in comorbidities and those connected to other viral infections. The research highlights 40 prey proteins that may be targeted by different pathogens, based on their evolutionary properties. The SARS-CoV-2 proteins and gene functions described are based on homologous genes from other coronaviruses, mainly SARS-CoV and MERS-CoV. The study also notes that not all proteins have been verified to be expressed or functional during SARS-CoV-2 infections, and thus, the subnetworks of these proteins are reported with caution. The study provides a detailed review of the principal interactions for each bait, along with interactive network maps and data tables for public access. The structural proteins of SARS-CoV-2 include S (spike), E (envelope), M (membrane), and N (nucleocapsid). S is a class I fusion protein that mediates viral entry, while E is involved in virus morphogenesis and assembly. M is the major driver for virus assembly and budding, and N binds to the viral RNA genome. The non-structural proteins include Nsp1 to Nsp16, which are involved in various functions such as RNA replication, capping, and processing. The study also identifies open reading frames (ORFs) like Orf3a, Orf6, and Orf9b, which are involved in pathogenesis and immune evasion. The study also explores the interactions of SARS-CoV-2 with host proteins, including those involved in immune response, cell death, and viral replication. For example, the S protein interacts with GOLGA7-ZDHHC5, a protein acyl-transferase complex, while the E protein interacts with host proteins such as AP31B, BRD2, and BRD4. The M protein interacts with host proteins involved in autophagy and endosomal trafficking, while the N protein interacts with proteins involved in stress granule formation and mRNA processing. The study also highlights the potential of targeting host proteins such as CK2 and HDAC2 for antiviral therapy. The findings provide a comprehensive map of SARS-CoV-2 interactions with host proteins, offering potential targets for drug repurposing and therapeutic development.This study identifies 332 high-confidence host-pathogen protein-protein interactions (PPIs) between SARS-CoV-2 and human proteins, focusing on prey proteins involved in comorbidities and those connected to other viral infections. The research highlights 40 prey proteins that may be targeted by different pathogens, based on their evolutionary properties. The SARS-CoV-2 proteins and gene functions described are based on homologous genes from other coronaviruses, mainly SARS-CoV and MERS-CoV. The study also notes that not all proteins have been verified to be expressed or functional during SARS-CoV-2 infections, and thus, the subnetworks of these proteins are reported with caution. The study provides a detailed review of the principal interactions for each bait, along with interactive network maps and data tables for public access. The structural proteins of SARS-CoV-2 include S (spike), E (envelope), M (membrane), and N (nucleocapsid). S is a class I fusion protein that mediates viral entry, while E is involved in virus morphogenesis and assembly. M is the major driver for virus assembly and budding, and N binds to the viral RNA genome. The non-structural proteins include Nsp1 to Nsp16, which are involved in various functions such as RNA replication, capping, and processing. The study also identifies open reading frames (ORFs) like Orf3a, Orf6, and Orf9b, which are involved in pathogenesis and immune evasion. The study also explores the interactions of SARS-CoV-2 with host proteins, including those involved in immune response, cell death, and viral replication. For example, the S protein interacts with GOLGA7-ZDHHC5, a protein acyl-transferase complex, while the E protein interacts with host proteins such as AP31B, BRD2, and BRD4. The M protein interacts with host proteins involved in autophagy and endosomal trafficking, while the N protein interacts with proteins involved in stress granule formation and mRNA processing. The study also highlights the potential of targeting host proteins such as CK2 and HDAC2 for antiviral therapy. The findings provide a comprehensive map of SARS-CoV-2 interactions with host proteins, offering potential targets for drug repurposing and therapeutic development.