Nisoldipine Inhibits Influenza A Virus Infection by Interfering with Virus Internalization Process

Abstract

Influenza virus infections and the continuing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are global public health concerns. As there are limited therapeutic options available in clinical practice, the rapid development of safe, effective and globally available antiviral drugs is crucial. Drug repurposing is a therapeutic strategy used in treatments for newly emerging and re-emerging infectious diseases. It has recently been shown that the voltage-dependent Ca2+ channel Cav1.2 is critical for influenza A virus entry, providing a potential target for antiviral strategies. Nisoldipine, a selective Ca2+ channel inhibitor, is commonly used in the treatment of hypertension. Here, we assessed the antiviral potential of nisoldipine against the influenza A virus and explored the mechanism of action of this compound. We found that nisoldipine treatment could potently inhibit infection with multiple influenza A virus strains. Mechanistic studies further revealed that nisoldipine impaired the internalization of the influenza virus into host cells. Overall, our findings demonstrate that nisoldipine exerts antiviral effects against influenza A virus infection and could serve as a lead compound in the design and development of new antivirals.

Broad-Spectrum Antivirals Derived from Natural Products

“…Reports have shown that the Ca 2+ channel as a host cell surface receptor, mediates the entry of IAV [ 42 , 43 ]. Indeed, the selective Ca 2+ channel inhibitor nisoldipine has been shown to inhibit the influenza A virus by impairing the internalization of the influenza virus into host cells [ 44 ] ( Figure 2 ).…”