Ciclopirox inhibits SARS-CoV-2 replication by promoting the degradation of the nucleocapsid protein

• DOI: 10.1016/j.apsb.2024.03.009
• Publication Date: 2024-03-12T02:20:38Z
• Authors: Xiafei Wei; Yuzheng Zhou; Xiaotong Shen; Lujie Fan; Donglan Liu; Xiang Gao; Jian Zhou; Yezi Wu; Yunfei Li; Wei Feng; Zheng Zhang
• Keywords: Replication; Drug Development

The nucleocapsid protein (NP) plays a crucial role in SARS-CoV-2 replication and is the most abundant structural with long half-life. Despite its vital severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assembly host inflammatory response, it remains an unexplored target for drug development. In this study, we identified small-molecule compound (ciclopirox) that promotes NP degradation using FDA-approved library drug-screening cell model. Ciclopirox significantly inhibited both vitro vivo by inducing degradation. induced abnormal aggregation through indirect interaction, leading to formation of condensates higher viscosity lower mobility. These were subsequently degraded via autophagy-lysosomal pathway, ultimately resulting shortened half-life reduced expression. Our results suggest potential target, ciclopirox holds substantial promise further development combat replication.