Publication date: Aug 21, 2026
Temperature varies across the nasal cavity, lower respiratory tract, and during febrile conditions, yet the impact of these differences on SARS-CoV-2 replication remains poorly understood. Here, we show that ancestral SARS-CoV-2, Delta, or Omicron BA. 5 variants replicate most efficiently at 37^0C. We found that transient receptor potential vanilloid 4 (TRPV4)-mediated calcium influx, a thermosensitive cation channel known to be activated at 37^0C, contributes to efficient SARS-CoV-2 replication. In addition, a calcineurin inhibitor, cyclosporine A (Cys A), and manidipine, an FDA-approved calcium channel blocker, both suppressed viral replication and protected Syrian hamsters from lethal infection with the SARS-CoV-2 Delta variant. Notably, a selective TRPV4 antagonist also conferred protection in infected hamsters. These results suggest that TRPV4-mediated calcium influx contributes to efficient SARS-CoV-2 replication at 37^0C and highlight manidipine as a strong candidate for repurposing as an anti-SARS-CoV-2 therapeutic.
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| Concepts | Keywords |
|---|---|
| Calcium | 37c |
| Fda | Calcium |
| Hamsters | Channel |
| Lethal | Contributes |
| Trpv4 | Cov |
| Delta | |
| Efficient | |
| Hamsters | |
| Influx | |
| Manidipine | |
| Mediated | |
| Replication | |
| Sars | |
| Temperature | |
| Trpv4 |
Semantics
| Type | Source | Name |
|---|---|---|
| drug | DRUGBANK | Calcium |
| drug | DRUGBANK | L-Cysteine |
| drug | DRUGBANK | Manidipine |
| pathway | KEGG | Viral replication |
| disease | MESH | infection |
| disease | MESH | Viral Infection |
| disease | MESH | Infectious Diseases |
| drug | DRUGBANK | Ciclosporin |
| disease | MESH | COVID 19 |
| disease | MESH | strains |
| disease | MESH | influenza |
| disease | MESH | fever |
| drug | DRUGBANK | Tretamine |
| pathway | REACTOME | Reproduction |
| drug | DRUGBANK | Methyldopa |