The continuous emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) variants and the increasing number of breakthrough infection cases among vaccinated people support the urgent need for research and development of antiviral drugs. Viral entry is an intriguing target for antiviral drug development. We found that diltiazem, a blocker of the L-type calcium channel Cav1.2 pore-forming subunit (Cav1.2 α1c) and an FDA-approved drug, inhibits the binding and internalization of SARS-CoV-2, and decreases SARS-CoV-2 infection in cells and mouse lung. Cav1.2 α1c interacts with SARS-CoV-2 spike protein and ACE2, and affects the attachment and internalization of SARS-CoV-2. Our finding suggests that diltiazem has potential as a drug against SARS-CoV-2 infection and that Cav1.2 α1c is a promising target for antiviral drug development for COVID-19.

For most viruses, cell entry involves engagement with many distinct plasma membrane components, each of which is essential. After binding to its specific receptor(s), rabies virus (RABV) enters host cells through the process of clathrin-mediated endocytosis.

Cotton fibers are single cells that show a relatively independent developmental process of cell differentiation, elongation, and secondary wall deposition. Auxin promotes fiber cell protrusion from the surface of the ovule. However, the role of auxin at other stages of cotton fiber development remains largely unknown. To gain a deeper insight into this aspect, we measured indoleacetic acid (IAA) content in developing fibers. Results showed an increase in IAA content at the transition stage from elongation to secondary cell wall deposition. Subsequently, we investigated the differences between two transgenic cottons that show upregulated and downregulated fiber auxin levels, respectively. In planta analysis revealed that, in addition to promoting cell elongation, auxin regulated the time of initiation of reactive oxygen species (ROS) production and secondary wall deposition in cotton fibers. This was closely correlated with the upregulated expression of GhRAC13, which regulates ROS-triggered cellulose synthesis. We found multiple putative auxin-responsive elements existed within the promoter region of GhRAC13, and IAA could induce proGhRAC13 activity. The dualluciferase reporter assay further proved the activation of proGhRAC13 by GhARF5, an auxin-signaling activator. Altogether, our results suggest a role of auxin in promoting the onset of secondary growth by directly upregulating GhRAC13 expression in cotton fibers.