Study Uncovers Antiviral Potential of Cilnidipine for Emergency Use in Flu Outbreaks

The influenza A virus remains a major global health concern due to its role in seasonal outbreaks and its potential to trigger pandemics. Existing antiviral treatments are often limited by drug resistance and reduced effectiveness, underscoring the need for new therapeutic approaches. Repurposing approved drugs with established safety profiles offers a practical solution. Given the critical role of calcium (Ca²⁺) in IAV infection, calcium channel blockers (CCBs) have emerged as promising antiviral candidates for further investigation.

Against the above background, Xin Chen, Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China, and colleagues explore the antiviral effects of cilnidipine against IAV both in vitro and in vivo while uncovering its underlying mechanism of action.

For this purpose, the researchers assessed the in vitro antiviral activity of cilnidipine using MTT assays, qRT-PCR, plaque assays, and western blotting. To investigate the mechanism of action, they conducted time-of-addition, viral internalization, pseudovirus neutralization, and HA syncytium assays. In vivo, BALB/c mice were intranasally infected with the virus to evaluate cilnidipine’s effects on viral titers, lung index, pulmonary inflammation, and survival rate.

The study led to the following findings:

• In vitro, cilnidipine shows antiviral activity against the influenza A virus (IAV) during the early stages of infection.
• It inhibits IAV internalization by disrupting clathrin- and caveolin-mediated endocytosis.
• Cilnidipine interferes with virus membrane fusion by targeting the HA2 subunit of the viral hemagglutinin.
• It suppresses IAV-induced activation of the PI3K-AKT and p38 MAPK signaling pathways.
• In vivo, cilnidipine lowers viral titers and lung index in infected mice.
• It improves lung pathology and reduces pulmonary inflammatory mediator expression.
• Cilnidipine treatment leads to improved survival rates in infected mice.

The study demonstrates that cilnidipine possesses strong antiviral effects against influenza A virus in both in vitro and in vivo settings, the researchers noted. They explained that by blocking clathrin- and caveolin-mediated endocytosis, targeting the HA2 subunit to prevent viral fusion, and modulating key signaling pathways such as PI3K-AKT and p38 MAPK, cilnidipine effectively disrupts critical steps of viral entry and replication.

These findings, they concluded, support its potential as a repurposed therapeutic option for managing influenza outbreaks.

Reference:

Li, Y., Yang, S., Jiang, F. et al. Cilnidipine exerts antiviral effects in vitro and in vivo by inhibiting the internalization and fusion of the influenza A virus. BMC Med 23, 200 (2025). https://doi.org/10.1186/s12916-025-04022-0