tetano
Editor, Senior Moderator
Nat Commun
. 2026 May 11.
doi: 10.1038/s41467-026-72938-z. Online ahead of print.
Inhibition of host N-myristoylation compromises the infectivity of SARS-CoV-2 due to Golgi-bypassing egress
Saber H Saber[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Nyakuoy Yak[SUP] #[/SUP][SUP] 1 2 [/SUP], Konstantin Dolski[SUP] 4 [/SUP], Sanna Mäki[SUP] 4 [/SUP], Lev Levanov[SUP] 4 [/SUP], Levina A Willenbrink[SUP] 4 [/SUP], Julian D J Sng[SUP] 5 [/SUP], Mohammed R Shaker[SUP] 1 [/SUP], Sean D Morrison[SUP] 1 [/SUP], Huiwen Zheng[SUP] 1 [/SUP], Selin Pars[SUP] 1 [/SUP], Giovanni Pietrogrande[SUP] 1 [/SUP], Yih Tyng Bong[SUP] 4 [/SUP], Tania Vane-Tempest[SUP] 4 [/SUP], Teemu Smura[SUP] 4 [/SUP], Tomas Strandin[SUP] 4 [/SUP], Ravi Ojha[SUP] 4 [/SUP], Ravi Kant[SUP] 4 6 7 [/SUP], Janika Ruuska[SUP] 4 [/SUP], Francesco Topi[SUP] 4 [/SUP], Diana Vaskiv[SUP] 4 [/SUP], Lauri Kareinen[SUP] 4 8 [/SUP], Tobias Binder[SUP] 1 [/SUP], Siyuan Lu[SUP] 1 [/SUP], Matthias Floetenmeyer[SUP] 9 [/SUP], Bahaa Al-Mhanawi[SUP] 1 [/SUP], Yanshan Zhu[SUP] 5 [/SUP], Tarja Sironen[SUP] 4 6 [/SUP], Gert Hoy Talbo[SUP] 1 [/SUP], Kirsty R Short[SUP] 5 [/SUP], Wouter W Kallemeijn[SUP] 10 11 [/SUP], Roberto Solari[SUP] 12 [/SUP], Jessica Mar[SUP] 1 [/SUP], Edward W Tate[SUP] 10 11 [/SUP], Ashley J van Waardenberg[SUP] 13 [/SUP], Olli Vapalahti[SUP] 4 6 14 [/SUP], Ernst Wolvetang[SUP] 15 [/SUP], Giuseppe Balistreri[SUP] 16 17 [/SUP], Merja Joensuu[SUP] 18 [/SUP]
Affiliations
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.
. 2026 May 11.
doi: 10.1038/s41467-026-72938-z. Online ahead of print.
Inhibition of host N-myristoylation compromises the infectivity of SARS-CoV-2 due to Golgi-bypassing egress
Saber H Saber[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Nyakuoy Yak[SUP] #[/SUP][SUP] 1 2 [/SUP], Konstantin Dolski[SUP] 4 [/SUP], Sanna Mäki[SUP] 4 [/SUP], Lev Levanov[SUP] 4 [/SUP], Levina A Willenbrink[SUP] 4 [/SUP], Julian D J Sng[SUP] 5 [/SUP], Mohammed R Shaker[SUP] 1 [/SUP], Sean D Morrison[SUP] 1 [/SUP], Huiwen Zheng[SUP] 1 [/SUP], Selin Pars[SUP] 1 [/SUP], Giovanni Pietrogrande[SUP] 1 [/SUP], Yih Tyng Bong[SUP] 4 [/SUP], Tania Vane-Tempest[SUP] 4 [/SUP], Teemu Smura[SUP] 4 [/SUP], Tomas Strandin[SUP] 4 [/SUP], Ravi Ojha[SUP] 4 [/SUP], Ravi Kant[SUP] 4 6 7 [/SUP], Janika Ruuska[SUP] 4 [/SUP], Francesco Topi[SUP] 4 [/SUP], Diana Vaskiv[SUP] 4 [/SUP], Lauri Kareinen[SUP] 4 8 [/SUP], Tobias Binder[SUP] 1 [/SUP], Siyuan Lu[SUP] 1 [/SUP], Matthias Floetenmeyer[SUP] 9 [/SUP], Bahaa Al-Mhanawi[SUP] 1 [/SUP], Yanshan Zhu[SUP] 5 [/SUP], Tarja Sironen[SUP] 4 6 [/SUP], Gert Hoy Talbo[SUP] 1 [/SUP], Kirsty R Short[SUP] 5 [/SUP], Wouter W Kallemeijn[SUP] 10 11 [/SUP], Roberto Solari[SUP] 12 [/SUP], Jessica Mar[SUP] 1 [/SUP], Edward W Tate[SUP] 10 11 [/SUP], Ashley J van Waardenberg[SUP] 13 [/SUP], Olli Vapalahti[SUP] 4 6 14 [/SUP], Ernst Wolvetang[SUP] 15 [/SUP], Giuseppe Balistreri[SUP] 16 17 [/SUP], Merja Joensuu[SUP] 18 [/SUP]
Affiliations
- PMID: 42115621
- DOI: 10.1038/s41467-026-72938-z
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.