Engineered Intranasal Virus Trap Provides Effective Protection Against SARS‐CoV‐2 Infection in Hamsters

Abstract

<p>As face masks are no longer required in many public areas, SARS-CoV-2 continues to spread and pose health risks to vulnerable populations such as children, the elderly, and immunocompromised individuals. This study presents the development of an Fn-LCB1-based engineered intranasal virus trap (EIVT) designed to capture and neutralize multiple SARS-CoV-2 variants, limiting viral infection and transmission. Fn-LCB1, a fusion protein consisting of an Fn domain that binds to fibronectin and an LCB1 domain with high affinity for the Spike protein receptor-binding domain (RBD) of SARS-CoV-2 viruses, can be produced on a large scale and purified in soluble form with high thermal stability. In vitro experiments demonstrated the efficient neutralization of SARS-CoV-2 wildtype and several variants, including Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529) by Fn-LCB1. Additionally, Fn-LCB1 effectively protected against SARS-CoV-2 Delta infection in a noncontact viral transmission Syrian hamster model. This study establishes Fn-LCB1 as a potent prophylactic agent against SARS-CoV-2 in vitro and in vivo, and serves as a proof-of-concept for the application of intranasal proteins to capture respiratory viruses and reduce live cell infections by competing with viral receptors.<br></p>