The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Antiangiogenesis therapy is one of the most common anticancer therapies. Bevacizumab is a monoclonal antibody that blocks the binding of the vascular endothelial growth factor to its high-affinity receptors. It is the only antiangiogenic agent approved for the first-line treatment of advanced non-small cell lung cancer (NSCLC). Many recent studies have attempted to determine the suit-able partners of bevacizumab in first-line treatment of NSCLC and evaluate its efficacy and safety as a second-line or beyond and con-tinuous treatment of beyond disease progression in patients with advanced NSCLC. This review summarizes current clinical research about the efficacy and safety of bevacizumab in the treatment of advanced NSCLC.