Harringtonine: A more effective antagonist for Omicron variant.

ABSTRACT: Fusion with host cell membrane is the main mechanism of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we propose that a new strategy to screen small-molecule antagonists blocking SARS-CoV-2 membrane fusion. Using cell membrane chromatography (CMC), we found that harringtonine (HT) simultaneously targeted SARS-CoV-2 S protein and host cell surface TMPRSS2 expressed by the host cell, and subsequently confirmed that HT can inhibit membrane fusion. HT effectively blocked SARS-CoV-2 original strain entry with the IC₅₀ of 0.217 μM, while the IC₅₀ in delta variant decreased to 0.101 μM, the IC₅₀ in Omicron BA.1 variant was 0.042 μM. Due to high transmissibility and immune escape, Omicron subvariant BA.5 has become the dominant st

SUBMITTER: Hu S 

PROVIDER: S-EPMC10195862 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature