tetano
Editor, Senior Moderator
Nat Commun
. 2025 Jul 9;16(1):6326.
doi: 10.1038/s41467-025-61431-8. Host protein ARF1 is a proviral factor for SARS-CoV-2 and a candidate broad-spectrum therapeutic target
Cunhuan Zhang[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuan-Qin Min[SUP] #[/SUP][SUP] 1 3 [/SUP], Heng Xue[SUP] 1 2 [/SUP], Haiyan Zhang[SUP] 1 3 [/SUP], Kunpeng Liu[SUP] 1 2 [/SUP], Yichao Tian[SUP] 1 2 [/SUP], Ziying Yang[SUP] 1 2 [/SUP], Zihan Zhao[SUP] 1 2 [/SUP], Hang Yang[SUP] 1 3 [/SUP], Chao Shan[SUP] 1 3 [/SUP], Xiulian Sun[SUP] 4 5 [/SUP], Yun-Jia Ning[SUP] 6 7 8 [/SUP]
Affiliations
SARS-CoV-2 and its emerging variants pose continuing threats to public health. SARS-CoV-2 assembles at the ER-Golgi intermediate compartment (ERGIC), where the viral membrane (M) protein highly accumulates to act as the central driver. However, how M is concentrated in the ERGIC, which hosts factor(s), may be involved, and whether they could be exploited as broad-spectrum antiviral targets remains unclear. Here, we identify an M-interacting host protein, ARF1, as a proviral factor that bolsters the propagation of SARS-CoV-2 and its variants in cultured cells and the viral infection and pathogenicity in female K18-hACE2 mice. By its N-terminal helix, ARF1 interacts with M and facilitates M's ERGIC accumulation and thus M-driven virion production. Consistently, pharmacological ARF1 inhibition by small molecules disrupts both ARF1 and M concentration at the ERGIC, blocking virion assembly and propagation. Furthermore, a designed peptide mimicking the M-targeted motif of ARF1 competitively blocks M-ARF1 interaction, M accumulation at the ERGIC, and viral assembly and propagation in vitro. Moreover, the peptidomimetic inhibitor exhibits therapeutic efficacy against SARS-CoV-2 infection and pathogenicity in vivo. These findings provide critical insights into the basic biology of SARS-CoV-2 and demonstrate the potential to develop pan-SARS-CoV-2 therapeutics by targeting ARF1 and/or the ARF1-M interaction interface.
. 2025 Jul 9;16(1):6326.
doi: 10.1038/s41467-025-61431-8. Host protein ARF1 is a proviral factor for SARS-CoV-2 and a candidate broad-spectrum therapeutic target
Cunhuan Zhang[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuan-Qin Min[SUP] #[/SUP][SUP] 1 3 [/SUP], Heng Xue[SUP] 1 2 [/SUP], Haiyan Zhang[SUP] 1 3 [/SUP], Kunpeng Liu[SUP] 1 2 [/SUP], Yichao Tian[SUP] 1 2 [/SUP], Ziying Yang[SUP] 1 2 [/SUP], Zihan Zhao[SUP] 1 2 [/SUP], Hang Yang[SUP] 1 3 [/SUP], Chao Shan[SUP] 1 3 [/SUP], Xiulian Sun[SUP] 4 5 [/SUP], Yun-Jia Ning[SUP] 6 7 8 [/SUP]
Affiliations
- PMID: 40634337
- PMCID: PMC12241596
- DOI: 10.1038/s41467-025-61431-8
SARS-CoV-2 and its emerging variants pose continuing threats to public health. SARS-CoV-2 assembles at the ER-Golgi intermediate compartment (ERGIC), where the viral membrane (M) protein highly accumulates to act as the central driver. However, how M is concentrated in the ERGIC, which hosts factor(s), may be involved, and whether they could be exploited as broad-spectrum antiviral targets remains unclear. Here, we identify an M-interacting host protein, ARF1, as a proviral factor that bolsters the propagation of SARS-CoV-2 and its variants in cultured cells and the viral infection and pathogenicity in female K18-hACE2 mice. By its N-terminal helix, ARF1 interacts with M and facilitates M's ERGIC accumulation and thus M-driven virion production. Consistently, pharmacological ARF1 inhibition by small molecules disrupts both ARF1 and M concentration at the ERGIC, blocking virion assembly and propagation. Furthermore, a designed peptide mimicking the M-targeted motif of ARF1 competitively blocks M-ARF1 interaction, M accumulation at the ERGIC, and viral assembly and propagation in vitro. Moreover, the peptidomimetic inhibitor exhibits therapeutic efficacy against SARS-CoV-2 infection and pathogenicity in vivo. These findings provide critical insights into the basic biology of SARS-CoV-2 and demonstrate the potential to develop pan-SARS-CoV-2 therapeutics by targeting ARF1 and/or the ARF1-M interaction interface.