Inhibition of host N-myristoylation compromises the infectivity of SARS-CoV-2 due to Golgi-bypassing egress
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus disease 2019 (COVID-19) pandemic, remains a global health concern despite vaccines, neutralizing antibodies, and antiviral drugs. The emergence of viral mutations that diminish the effectiveness of current interventions underscores the importance of alternative, host-directed strategies. Here, we show that pharmacological inhibition or knockdown of host N-myristoyltransferase 1 (NMT1), one of the two human enzymes that mediates protein N-myristoylation, significantly impairs SARS-CoV-2, Vesicular Stomatitis Virus (VSV) and Respiratory syncytial virus (RSV) infections. We demonstrate the antiviral efficacy and safety of this host-directed therapeutic strategy across multiple viral tropic sites, including human lung adenocarcinoma cell lines, primary nasal epithelial cells, and human choroid plexus-cortical brain organoids. NMT1 inhibition triggers a Golgi-bypassing pathway for SARS-CoV-2 progeny virion egress, through endoplasmic reticulum and lysosomal structures, which leads to perturbed progeny virion composition and spike maturation, impairing progeny virion infectivity.
Authors
- Julian D. J. Sng (ORCID: https://orcid.org/0000-0001-7837-4473)
- Giovanni Pietrogrande (ORCID: https://orcid.org/0000-0001-5107-2002)
- Giuseppe Balistreri (ORCID: https://orcid.org/0000-0002-3585-559X)
- Gert Talbo
- Matthias Floetenmeyer (ORCID: https://orcid.org/0000-0002-0133-1632)
- Selin Pars (ORCID: https://orcid.org/0009-0003-9618-7956)
- Janika Ruuska (ORCID: https://orcid.org/0000-0002-3978-2033)
- Sean D. Morrison (ORCID: https://orcid.org/0000-0001-9128-8713)
- Kirsty Short (ORCID: https://orcid.org/0000-0002-2677-1271)
- Diana Vaskiv
- T. Binder
- Yih Tyng Bong
- Tania Vane-Tempest
- Tomas Strandin
- Teemu Smura
- Saber H. Saber
- Yanshan Zhu
- Levina A. Willenbrink
- Ravi Ojha
- Sanna Mäki (ORCID: https://orcid.org/0009-0006-9455-8778)
- Bahaa Al-mhanawi
- Francesco Topi
- Edward W. Tate (ORCID: https://orcid.org/0000-0003-2213-5814)
- Ernst Wolvetang (ORCID: https://orcid.org/0000-0002-2146-6614)
- Lauri Kareinen (ORCID: https://orcid.org/0000-0003-2525-7817)
- Siyuan Lu
- Lev Levanov
- Olli Vapalahti (ORCID: https://orcid.org/0000-0003-2270-6824)
- Merja Joensuu (ORCID: https://orcid.org/0000-0002-4533-0455)
- Mohammed R. Shaker (ORCID: https://orcid.org/0000-0002-3675-4598)
- Wouter W. Kallemeijn
- Ravi Kant (ORCID: https://orcid.org/0000-0003-3878-9775)
- Tarja Sironen (ORCID: https://orcid.org/0000-0002-2344-2755)
- Nyakuoy Yak (ORCID: https://orcid.org/0000-0001-9412-4300)
- Huiwen Zheng
- Jessica Mar
- Roberto Solari
- Konstantin Dolski
- Ashley J. van Waardenberg (ORCID: https://orcid.org/0000-0002-9382-7490)
Institutions
- University of Helsinki (FI)
- The University of Queensland (AU)
- Australian Housing and Urban Research Institute (AU)
- Helsinki University Hospital (FI)
- The Francis Crick Institute (GB)
- Finnish Food Authority (FI)
- Maritime Institute in Gdansk (PL)
- Imperial College London (GB)
- Gdańsk Medical University (PL)
- Assiut University (EG)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-11
- DOI
- https://doi.org/10.1038/s41467-026-72938-z
- Primary Topic
- Cellular transport and secretion
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Helsingin Yliopisto
- University of Queensland
- Biocenter Finland
- Helsinki Institute of Life Science, Helsingin Yliopisto
- Queensland Brain Institute