Cellular lipids: fundamental host factors for monkeypox virus replication and pathogenesis.

The recent outbreaks of mpox and other poxvirus diseases worldwide have highlighted the critical need for effective antiviral treatments. Throughout its life cycle, MPXV, a member of the Orthopoxvirus genus, takes advantage of the host’s lipid metabolism. In addition to being essential for maintaining cellular homeostasis, lipids are also used by viruses for entrance, reproduction, assembly, and egress. Lipid rafts (LRs), membrane microdomains rich in cholesterol that are essential for viral entry and viral envelope structure, are a crucial component of this exploitation. This study summarizes evidence that MPXV uses lipid signaling, metabolism, and compartmentalization, with an emphasis on cholesterol-rich LRs as crucial life-cycle platforms. We use analogies from related poxviruses to assess our current understanding of these lipid-centric processes comprehensively. The possibility for repurposing lipid-lowering medications, such as statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as adjuvant antiviral therapy is another significant translational consequence highlighted in the paper. These medications provide a viable, host-directed approach to supplement current direct antivirals by interfering with host lipid pathways required by MPXV. We review the current preclinical data, the mechanistic rationale, and key issues for further study of this treatment strategy.