A Tetrapodal Tryptophan Derivative with Multiple Exposed Free Carboxylic Acids Blocks Host Cell Entry of Omicron SARS-Cov-2 and Respiratory Syncytial Virus.

ABSTRACT: Omicron sublineages of SARS-CoV-2 have accelerated the spread of the virus and facilitated immune escape. In this work, we demonstrate that compound 2, a potent HIV and enterovirus A71 (EV-A71) entry inhibitor previously discovered in our research group, also displays potent in vitro activity against different SARS-CoV-2 Omicron variants while showing no activity against the ancestral SARS-CoV-2 Wuhan strain. Moreover, its sodium salt (2-Na salt) exhibited in vivo antiviral activity in a murine model of Omicron BA.1. infection. Indeed, biophysical and cryo-EM studies revealed binding of 2-Na salt to the Omicron BA.1 spike (S) protein stabilizing a "closed" form in which ∼75% of the S particles have all RBDs down, unlike the usual "open" form with one RBD

SUBMITTER: Marti-Mari O 

PROVIDER: S-EPMC12658634 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature