TY - JOUR
T1 - Inhibition of host N-myristoylation compromises the infectivity of SARS-CoV-2 due to Golgi-bypassing egress
AU - Saber, Saber H.
AU - Yak, Nyakuoy
AU - Dolski, Konstantin
AU - Mäki, Sanna
AU - Levanov, Lev
AU - Willenbrink, Levina A.
AU - Sng, Julian D.J.
AU - Shaker, Mohammed R.
AU - Morrison, Sean D.
AU - Zheng, Huiwen
AU - Pars, Selin
AU - Pietrogrande, Giovanni
AU - Bong, Yih Tyng
AU - Vane-Tempest, Tania
AU - Smura, Teemu
AU - Strandin, Tomas
AU - Ojha, Ravi
AU - Kant, Ravi
AU - Ruuska, Janika
AU - Topi, Francesco
AU - Vaskiv, Diana
AU - Kareinen, Lauri
AU - Binder, Tobias
AU - Lu, Siyuan
AU - Floetenmeyer, Matthias
AU - Al-mhanawi, Bahaa
AU - Zhu, Yanshan
AU - Sironen, Tarja
AU - Talbo, Gert Hoy
AU - Short, Kirsty R.
AU - Kallemeijn, Wouter W.
AU - Solari, Roberto
AU - Mar, Jessica
AU - Tate, Edward W.
AU - van Waardenberg, Ashley J.
AU - Vapalahti, Olli
AU - Wolvetang, Ernst
AU - Balistreri, Giuseppe
AU - Joensuu, Merja
N1 - Publisher Copyright:
© The Author(s) 2026.
PY - 2026/12
Y1 - 2026/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105045375113
U2 - 10.1038/s41467-026-72938-z
DO - 10.1038/s41467-026-72938-z
M3 - Article
C2 - 42115621
AN - SCOPUS:105045375113
SN - 2041-1723
VL - 17
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7055
ER -