tetano
Editor, Senior Moderator
iScience
. 2026 Mar 11;29(4):115334.
doi: 10.1016/j.isci.2026.115334. eCollection 2026 Apr 17.
CGM23 corresponds to a pan-coronavirus lipopeptide inhibitor potently inhibiting virion fusion
Yusuke Matsui[SUP] 1 2 [/SUP], Roland Schwarzer[SUP] 1 2 3 [/SUP], Mauricio Montano[SUP] 1 2 [/SUP], Ekram W Helmy[SUP] 1 2 [/SUP], Rahul K Suryawanshi[SUP] 1 4 [/SUP], Taha Y Taha[SUP] 1 2 5 [/SUP], Yan Wang[SUP] 6 [/SUP], Yvonne Angel[SUP] 6 [/SUP], Marc Adler[SUP] 6 [/SUP], M Flori Sassano[SUP] 7 [/SUP], Hyunil Jo[SUP] 8 [/SUP], Robert Tarran[SUP] 7 [/SUP], Melanie Ott[SUP] 1 2 9 [/SUP], Warner C Greene[SUP] 1 2 9 10 [/SUP]
Affiliations
We developed a pan-coronavirus lipopeptide fusion inhibitor, CGM23, which binds to the highly conserved spike heptad repeat-1 domain, thus interrupting the formation of the six-helix bundle required for membrane fusion. In vitro, CGM23 potently inhibited infection by all human coronaviruses tested, including SARS-CoV, MERS-CoV, and SARS-CoV-2 and the seasonal coronaviruses. CGM23 is based on the amino acid sequence of SARS-CoV-2 spike protein. Computational modeling, 4-phenylbutanoic acid was appended to the N-terminus to mimic interactions with the hydrophobic pocket adjacent to the heptad repeat-2. A C-terminal addition of palmitic acid via a PEG linker enhanced CGM23's fusion inhibition. In a wild-type mouse model infected with mouse-adapted SARS-CoV-2, intranasal CGM23 prevented lung infection when given 30 min before challenge. Furthermore, therapeutic CGM23 8 h post-inoculation significantly reduced viral loads in the lungs. In summary, CGM23 represents a promising pan-coronavirus inhibitor with both potential therapeutic and prophylactic activity in humans.
Keywords: Biochemistry; Pharmacology; Virology.
. 2026 Mar 11;29(4):115334.
doi: 10.1016/j.isci.2026.115334. eCollection 2026 Apr 17.
CGM23 corresponds to a pan-coronavirus lipopeptide inhibitor potently inhibiting virion fusion
Yusuke Matsui[SUP] 1 2 [/SUP], Roland Schwarzer[SUP] 1 2 3 [/SUP], Mauricio Montano[SUP] 1 2 [/SUP], Ekram W Helmy[SUP] 1 2 [/SUP], Rahul K Suryawanshi[SUP] 1 4 [/SUP], Taha Y Taha[SUP] 1 2 5 [/SUP], Yan Wang[SUP] 6 [/SUP], Yvonne Angel[SUP] 6 [/SUP], Marc Adler[SUP] 6 [/SUP], M Flori Sassano[SUP] 7 [/SUP], Hyunil Jo[SUP] 8 [/SUP], Robert Tarran[SUP] 7 [/SUP], Melanie Ott[SUP] 1 2 9 [/SUP], Warner C Greene[SUP] 1 2 9 10 [/SUP]
Affiliations
- PMID: 41940347
- PMCID: PMC13049657
- DOI: 10.1016/j.isci.2026.115334
We developed a pan-coronavirus lipopeptide fusion inhibitor, CGM23, which binds to the highly conserved spike heptad repeat-1 domain, thus interrupting the formation of the six-helix bundle required for membrane fusion. In vitro, CGM23 potently inhibited infection by all human coronaviruses tested, including SARS-CoV, MERS-CoV, and SARS-CoV-2 and the seasonal coronaviruses. CGM23 is based on the amino acid sequence of SARS-CoV-2 spike protein. Computational modeling, 4-phenylbutanoic acid was appended to the N-terminus to mimic interactions with the hydrophobic pocket adjacent to the heptad repeat-2. A C-terminal addition of palmitic acid via a PEG linker enhanced CGM23's fusion inhibition. In a wild-type mouse model infected with mouse-adapted SARS-CoV-2, intranasal CGM23 prevented lung infection when given 30 min before challenge. Furthermore, therapeutic CGM23 8 h post-inoculation significantly reduced viral loads in the lungs. In summary, CGM23 represents a promising pan-coronavirus inhibitor with both potential therapeutic and prophylactic activity in humans.
Keywords: Biochemistry; Pharmacology; Virology.