The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.
【저자키워드】 fusion inhibitor, lipopeptide, 25-Hydroxycholesterol, human coronavirus, 【초록키워드】 SARS-CoV-2, SARS-COV-2 infection, COVID-19 pandemic, Infection, HCoV-OC43, variants of concern, peptide, antiviral activity, Newborn, mice, VOCs, CoV, HCoV-229E, cholesterol, inhibitor, Combination, Anti-SARS-CoV-2 Activity, global public health, human CoVs, Modification, CH25H, effective, synergistic, IMPROVE, PROTECT, caused, reported, peptide-based, feasible, 【제목키워드】 SARS-CoV-2, Human, activity, concern, Other, potent,