Desloratadine

In pseudotyped virus infection assays, the histamine H1 antagonists loratadine (LOR) and desloratadine (DES) prevented entry of SARS‑CoV‑2 spike pseudovirus into ACE2‑overexpressing cells, with DES being more effective. Cell membrane chromatography and surface plasmon resonance confirmed that both drugs bind to ACE2, with DES showing much stronger binding affinity. Molecular docking revealed that DES forms a hydrogen bond with LYS31, whereas LOR binds via non‑hydrogen bonds. This is the first demonstration that LOR and DES inhibit viral entry by blocking the spike‑ACE2 interaction, suggesting a potential repurposing strategy for COVID‑19.

Fig. 1 The binding character of LOR and DES with ACE2. (Hou Y, et al., 2021)

Desloratadine (DES) and benzoic acid (BA) formed a co‑amorphous salt (1:1) via melt‑quenching. Solid‑state analysis (DSC, FTIR, PXRD, PLM) confirmed a homogeneous amorphous system with strong ionic interactions and a single glass transition temperature higher than amorphous DES alone. The co‑amorphous system showed significantly higher dissolution rate and solubility than crystalline DES and remained physically stable for 3 months at 40°C/75% RH, whereas amorphous DES crystallized. This co‑amorphous salt strategy offers a promising approach to improve DES bioavailability.

Fig. 2 PXRD patterns of pure desloratadine (DES) (black line), pure benzoic acid (BA) (red line), physical mixture (blue line), pure amorphous DES (pink line), and co-amorphous DES–BA (green line). (Ainurofiq A, et al., 2018)