Work

Narciclasine inhibits vaccinia virus infection by activating the RhoA signaling pathway

Year: 2024

Type: article

Abstract: • Significance of the study: Our findings emphasize the role of narciclasine in inhibiting vaccinia virus (VACV), probably by activating RhoA. This study lays the groundwork for developing potential drugs targeting mpox virus (MPXV). • Scientific question: The global spread of the MPXV poses a significant public health threat. Although tecovirimat is the primary treatment for MPXV, instances of resistance to this drug have been reported in patients. What strategies can be employed to develop new inhibitors against MPXV? • Evidence before this study: Previous research on narciclasine has mainly focused on its application in cancer treatment, with occasional reports on its inhibitory effects on certain viruses. Narciclasine is known to activate the RhoA signaling pathway, promoting the formation of actin stress fibers. VACV serves as the prototype for poxvirus research. Inhibition of RhoA signaling is essential for VACV morphogenesis and extracellular enveloped virus (EEV) production. • New findings: This study presents novel insights into narciclasine. We discovered that narciclasine inhibits VACV EEV formation and subsequent viral spread. Furthermore, our research indicates that narciclasine-induced activation of RhoA suppresses VACV replication. These results suggest that RhoA agonists could potentially inhibit VACV. In 2022, a sharp rise in global cases of mpox virus (MPXV) led the World Health Organization (WHO) to declare it a public health emergency of international concern. However, progress in developing drugs targeting MPXV has been slow. Here, we investigate the natural alkaloid narciclasine as a potential inhibitor of poxviruses. Our investigation demonstrates that narciclasine at 40 nmol/L (nM) to 160 nM dosages effectively blocks vaccinia virus (VACV), a representative poxvirus. Specifically, narciclasine disrupts the production of extracellular enveloped virus (EEV), which is crucial for viral spread. Narciclasine’s antiviral impact is probably attributed to its activation of the RhoA signaling pathway. This study highlights narciclasine’s potential as a promising new therapeutic candidate against poxviruses, offering prospects for its development into a potent antiviral agent that is essential for combating emerging poxvirus outbreaks.

Source: Biosafety and Health

DOI: 10.1016/j.bsheal.2024.11.002

Authors: Ting Xu, Zhengyang Pan, Xue Li, Mengyang Zhao, Zichen Li, Leiliang Zhang

Institutions: Shandong Provincial QianFoShan Hospital, Shandong First Medical University

Language: English

Topic: Poxvirus research and outbreaks

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500