tetano
Editor, Senior Moderator
Virology
. 2025 Jun 12:610:110607.
doi: 10.1016/j.virol.2025.110607. Online ahead of print. SARS-CoV-2 host-pathogen interactome: insights into more players during pathogenesis
S A Mothae[SUP] 1 [/SUP], T E Chiliza[SUP] 2 [/SUP], N E Mvubu[SUP] 3 [/SUP]
Affiliations
SARS-CoV-2, the virus responsible for COVID-19, emerged in December 2019 and was declared a global health emergency in January 2020. The pandemic has led to nearly 7 million deaths worldwide, prompting ongoing research into viral variants and potential future outbreaks. Like other viruses, SARS-CoV-2 relies on host proteins to complete its life cycle, hijacking cellular processes to enhance replication and evade immune responses. The virus primarily enters host cells through the angiotensin-converting enzyme 2 (ACE2) receptor, but additional co-receptors, including C-type lectins, neuropilin-1, basigin (CD147), and tyrosine-protein kinase receptors, may also facilitate entry. To evade immune detection, SARS-CoV-2 targets the type I interferon (IFN) pathway, disrupting antiviral responses. Viral replication is supported by interactions with host polymerase (Pol δ), lipid droplet regulators, and Ras-related proteins. Non-structural proteins (NSPs) further manipulate host ATP metabolism and stress response pathways in the endoplasmic reticulum (ER) and mitochondria. The membrane (M) protein plays a crucial role in viral trafficking, interacting with host proteins to direct assembly at the ER-Golgi intermediate compartment (ERGIC) or plasma membrane, promoting syncytia formation. For viral release, SARS-CoV-2 exploits tight junction proteins, enhancing its spread within the lungs. This narrative review unpacks the SARS-CoV-2 host-pathogen interactome, highlighting critical structural and non-structural protein interactions as well as crucial host proteins that are expressed during the pathogenesis process. Through an integrative perspective of essential "players" during pathogenesis, this review aims to uncover therapeutic and vaccine targets, offering insights into antiviral strategies against SARS-CoV-2 and future coronaviruses.
Keywords: COVID-19; Interactome; Pathogenesis; Protein-protein interaction (PPI); SARS-CoV-2.
. 2025 Jun 12:610:110607.
doi: 10.1016/j.virol.2025.110607. Online ahead of print. SARS-CoV-2 host-pathogen interactome: insights into more players during pathogenesis
S A Mothae[SUP] 1 [/SUP], T E Chiliza[SUP] 2 [/SUP], N E Mvubu[SUP] 3 [/SUP]
Affiliations
- PMID: 40544703
- DOI: 10.1016/j.virol.2025.110607
SARS-CoV-2, the virus responsible for COVID-19, emerged in December 2019 and was declared a global health emergency in January 2020. The pandemic has led to nearly 7 million deaths worldwide, prompting ongoing research into viral variants and potential future outbreaks. Like other viruses, SARS-CoV-2 relies on host proteins to complete its life cycle, hijacking cellular processes to enhance replication and evade immune responses. The virus primarily enters host cells through the angiotensin-converting enzyme 2 (ACE2) receptor, but additional co-receptors, including C-type lectins, neuropilin-1, basigin (CD147), and tyrosine-protein kinase receptors, may also facilitate entry. To evade immune detection, SARS-CoV-2 targets the type I interferon (IFN) pathway, disrupting antiviral responses. Viral replication is supported by interactions with host polymerase (Pol δ), lipid droplet regulators, and Ras-related proteins. Non-structural proteins (NSPs) further manipulate host ATP metabolism and stress response pathways in the endoplasmic reticulum (ER) and mitochondria. The membrane (M) protein plays a crucial role in viral trafficking, interacting with host proteins to direct assembly at the ER-Golgi intermediate compartment (ERGIC) or plasma membrane, promoting syncytia formation. For viral release, SARS-CoV-2 exploits tight junction proteins, enhancing its spread within the lungs. This narrative review unpacks the SARS-CoV-2 host-pathogen interactome, highlighting critical structural and non-structural protein interactions as well as crucial host proteins that are expressed during the pathogenesis process. Through an integrative perspective of essential "players" during pathogenesis, this review aims to uncover therapeutic and vaccine targets, offering insights into antiviral strategies against SARS-CoV-2 and future coronaviruses.
Keywords: COVID-19; Interactome; Pathogenesis; Protein-protein interaction (PPI); SARS-CoV-2.