Proteomic Profiling of SARS-CoV-2 Virus-Host Interactions and Implications for Antiviral Drug Discovery
Year: 2025
Type: dissertation
Abstract: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a coronavirus that causes COVID-19. The virus rapidly spread into a global pandemic, and over the past five years, COVID-19 has claimed more than eight million lives and caused significant economic disruption. Although several antiviral agents, such as remdesivir and Paxlovid, have been approved for clinical use, only a limited number of effective antiviral drugs targeting SARS-CoV-2 are currently available. This doctoral thesis investigates the protein–protein interactions between SARS-CoV-2 and human host cells, which are critical for viral replication and immune evasion. The aim of this work is to enhance our understanding of the molecular mechanisms underlying virus–host interactions and to highlight the role of proteomics in antiviral drug discovery. The study employs methods such as affinity purification coupled with mass spectrometry (AP-MS) and proximity-dependent biotinylation (BioID) to identify host proteins that are exploited by the virus to support its replication. Mapping these interactions provides opportunities for drug repurposing by identifying existing compounds that may be effective against SARS-CoV-2. In addition, this thesis includes the development of a comprehensive "hijackome" database that compiles SARS-CoV-2–host protein interactions across multiple viral variants, including Alpha, Beta, Delta, and Omicron. Proteomic and phosphoproteomic analyses are used to investigate variant-specific differences in host cell manipulation, replication efficiency, and immune evasion strategies. This temporal and variant-level analysis provides novel insights into how emerging variants adapt to sustain infection and evade immune detection. The find-ings offer a scientific foundation for the development of new therapeutic strategies targeting SARS-CoV-2 and potentially other viral pathogens.
Source: Työväentutkimus Vuosikirja
Author: Huuskonen, Sini
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7197808541