A Palmitic Acid-Conjugated, Peptide-Based pan-CoV Fusion Inhibitor Potently Inhibits Infection of SARS-CoV-2 Omicron and Other Variants of Concern

Our previous studies have shown that cholesterol-conjugated, peptide-based pan-coronavirus (CoV) fusion inhibitors can potently inhibit human CoV infection. However, only palmitic acid (C16)-based lipopeptide drugs have been tested clinically, suggesting that the development of C16based lipopeptide drugs is feasible. Here, we designed and synthesized a C16-modified pan-CoV fusion inhibitor, EK1-C16, and found that it potently inhibited infection by SARS-CoV-2 and its variants of concern (VOCs), including Omicron, and other human CoVs and bat SARS-related CoVs (SARSr-CoVs). These results suggest that EK1-C16 could be further developed for clinical use to prevent and treat infection by the currently circulating MERS-CoV, SARS-CoV-2 and its VOCs, as well as any future emerging or re-emerging coronaviruses.

Automated summary

Cholesterol-conjugated, peptide-based pan-coronavirus fusion inhibitors have been shown to effectively inhibit human coronavirus infection. A newly developed lipopeptide drug called EK1-C16, modified with palmitic acid (C16), has demonstrated potent inhibition against SARS-CoV-2 and its variants, as well as other human CoVs and bat SARS-related CoVs. This suggests that EK1-C16 could be a promising candidate for the prevention and treatment of current and future coronaviruses.