Abstract
The COVID-19 pandemic generates a global threat to public health and continuously emerging SARS-CoV-2 variants bring a great challenge to the development of both vaccines and antiviral agents. In this study, we identified UA-18 and its optimized analog UA-30 via the hit-to-lead strategy as novel SARS-CoV-2 fusion inhibitors. The lead compound UA-30 showed potent antiviral activity against infectious SARS-CoV-2 (wuhan-HU-1 variant) in Vero-E6 cells and was also effective against infection of diverse pseudotyped SARS-CoV-2 variants with mutations in the S protein including the Omicron and Delta variants. More importantly, UA-30 might target the cavity between S1 and S2 subunits to stabilize the prefusion state of the SARS-CoV-2 S protein, thus leading to interfering with virus-cell membrane fusion. This study offers a set of novel SARS-CoV-2 fusion inhibitors against SARS-CoV-2 and its variants based on the 3-O-β-chacotriosyl UA skeleton.
Keywords: Membrane fusion; Pentacyclic triterpenoid saponins; SARS-CoV-2; SARs.
【저자키워드】 SARS-CoV-2, membrane fusion, SARS., Pentacyclic triterpenoid saponins, 【초록키워드】 public health, Vaccine, Mutation, S protein, COVID-19 pandemic, SARS, variant, SARS-CoV-2 variant, Infection, Delta, antiviral activity, omicron, inhibitors, variants, Cavity, Antiviral agents, membrane fusion, inhibitor, SARS-CoV-2 S protein, subunit, prefusion, offer, Vero-E6 cells, pseudotyped SARS-CoV-2, saponins, effective, virus-cell membrane fusion, S1 and S2, generate, the S protein, the SARS-CoV-2, Vero-E6 cell, 【제목키워드】 Spike protein, inhibitor, identification, SARS-CoV-2 entry, prefusion, derivative,