biostudies-literatureLiu DNIAID NIH HHSNIMHD NIH HHSHHS | NIH | National Institute on Minority Health and Health DisparitiesNCI NIH HHSNIGMS NIH HHSe0017124https://www.ebi.ac.uk/biostudies/studies/S-EPMC11019840biostudies-literatureUnknown98(4)The global impact of emerging viral infections emphasizes the urgent need for effective broad-spectrum antivirals. The cellular organelle, lipid droplet (LD), is utilized by many types of viruses for replication, but its reduction does not affect cell survival. Therefore, LD is a potential target for developing broad-spectrum antivirals. In this study, we found that 2-bromopalmitate (2 BP), a previously defined palmitoylation inhibitor, depletes LD across all studied cell lines and exerts remarkable antiviral effects on different coronaviruses. We comprehensively utilized 2 BP, alongside other palmitoylation inhibitors such as cerulenin and 2-fluoro palmitic acid (2-FPA), as well as the enhancer palmostatin B and evaluated their impact on LD and the replication of human coronaviruses (hCoVJournal of virology2-Bromopalmitate depletes lipid droplets to inhibit viral replication.PMC11019840G12 MD007597SC1 AI112785SC1 GM135050SC1 CA200517G12MD007597Cruz-Cosme RTang QLeibowitz JLiu DWu Yfalse2-Bromopalmitate depletes lipid droplets to inhibit viral replication.The global impact of emerging viral infections emphasizes the urgent need for effective broad-spectrum antivirals. The cellular organelle, lipid droplet (LD), is utilized by many types of viruses for replication, but its reduction does not affect cell survival. Therefore, LD is a potential target for developing broad-spectrum antivirals. In this study, we found that 2-bromopalmitate (2 BP), a previously defined palmitoylation inhibitor, depletes LD across all studied cell lines and exerts remarkable antiviral effects on different coronaviruses. We comprehensively utilized 2 BP, alongside other palmitoylation inhibitors such as cerulenin and 2-fluoro palmitic acid (2-FPA), as well as the enhancer palmostatin B and evaluated their impact on LD and the replication of human coronaviruses (hCoV2024-01-01T00:00:00Z2024 Apr2025-04-04T12:58:38.865Z2025-04-04T12:58:38.865ZS-EPMC110198403848836110.1128/jvi.00171-24