A Broad-Spectrum Antiviral Fusion Protein, Pheromonicin Demonstrated Protective Efficacy against SARS-CoV-2 Variants in vitro and in vivo Models

The unprecedented Coronavirus Disease (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective antiviral drug to control this severe infectious disease. Here, we found that the E or M membrane proteins of coronavirus could be targeted by a 28-residue antibody mimetic by fusing two antibody Fab Complementarity-Determining Regions (V_HCDR1 and V_LCDR3) through a cognate Framework Region (V_HFR2) of the antibodies which recognize the coronavirus E or M proteins. We constructed a fusion protein, Pheromonicin-COVID-19 (PMC-COVID-19), by linking colicin Ia, a bactericidal molecule produced by E. coli which kills target cells by forming a voltage-dependent channel in target lipid bilayers, to that antibody mimetic. The E or M protein/antibody mimetic interaction initiated the formation of irreversible PMC-COVID-19 channel in the COVID-19 envelope and viral-infected host cell membrane resulting in leakage of cellular contents. PMC-COVID-19 demonstrates broad-spectrum protective efficacy against tested SARS-CoV-2 variants-induced severe acute respiratory syndrome (p<0.01-0.0001). PMC-COVID-19 significantly altered outcomes of in vivo fatal COVID-19 challenge infection without evident toxicity, making it an appropriate candidate for further clinical evaluation.

Published Date: 2023-03-22; Received Date: 2023-02-20