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

Abstract

AbstractAs 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.