SARS-CoV-2 replication in Calu-3 cells

SARS-CoV-2 replication in Calu-3 cells refers to a phenotypic assay system rather than a single molecular target. Calu-3 is a human lung adenocarcinoma cell line that naturally expresses high levels of Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Protease Serine 2 (TMPRSS2), making it a physiologically relevant model for studying SARS-CoV-2 infection and replication in the human airway (Hoffmann et al., 2020, Cell). This assay measures the overall ability of the virus to complete its life cycle—including attachment, entry, genome replication, and egress—within a host cell environment. In drug discovery, this system is used to screen for antiviral compounds and determine their half-maximal effective concentration (EC50) (ChEMBL Assay CHEMBL4303835). Because it is a whole-cell assay, it captures the activity of drugs targeting various viral proteins, such as the RNA-dependent RNA polymerase (targeted by Remdesivir) or the Main Protease (targeted by Nirmatrelvir), as well as host factors required for viral propagation. While highly useful for identifying potent inhibitors, the readout represents a complex biological process rather than a specific protein-ligand interaction. Consequently, it is classified as a phenotypic target in pharmacological databases like ChEMBL and PubChem.

Other names

SARS-CoV-2 viral replication assayCalu-3 phenotypic antiviral assaySARS-CoV-2 inhibition in Calu-3SARS-CoV-2 growth in Calu-3

Drugs tested in this system typically act by inhibiting viral entry (e.g., TMPRSS2 inhibitors), viral proteases (e.g., Mpro inhibitors), or the viral RNA-dependent RNA polymerase (RdRp).