Potential blocker of SARS-CoV entry and a narrow functionality of its spike protein motifs on Qubevirus platform.

ABSTRACT: Targeted disruption of SARS-CoV entry remains a critical strategy in antiviral therapeutic design. Central to this process is the viral spike (S) protein, which mediates host recognition via interactions with the human angiotensin-converting enzyme 2 (hACE2). Here, we expand our previous work by identifying the smallest active spike (S) protein binding motif (RBSM) and key residues of SARS-CoV (S_473-492) that recognize hACE2. Using the Qubevirus (Qβ) platform, we validated five essential residues (L472, N473, N479, D480, and Y491) that are critical for SARS-CoV binding and entry. Qβ phage-displayed RBSM variants disrupted hACE2 recognition and infection initiation. An engineered RBSM insert containing all five mutant residues completely abolished recognition and binding to both

SUBMITTER: Dzelamonyuy A 

PROVIDER: S-EPMC12274811 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature