Fusion of SARS-CoV-2 neutralizing LCB1 peptide with Bacillus amyloliquefaciens RNase improves antiviral efficacy

Fusion of SARS-CoV-2 neutralizing LCB1 peptide with Bacillus amyloliquefaciens RNase improves antiviral efficacy

Abstract Virus-neutralizing peptides (VNPs) emerged as promising antiviral drug candidates with unprecedented specificity and cost-effectiveness during the recent COVID-19 pandemic. However, limited avidity, lack of effector functions, short circulatory half-life, and restricted administration route...

Full description

Saved in:
Bibliographic Details
Main Authors: Nikita N. Kostin, Tatyana V. Bobik, Elena V. Konovalova, Milita V. Kocharovskaya, Maria A. Simonova, Natalia Yu Rushkevich, Yuliana A. Mokrushina, George A. Skryabin, Roman S. Kalinin, Sergey I. Kovalchuk, Rustam H. Ziganshin, Leonid A. Kaluzhskiy, Oksana V. Gnedenko, Evgeniy O. Yablokov, Alexis S. Ivanov, Aleksandr S. Chernov, Vitaly A. Kazakov, Oksana N. Khokhlova, Arkady N. Murashev, Senlian Hong, Elena I. Shramova, Alexey A. Schulga, Ekaterina N. Lyukmanova, Mikhail P. Kirpichnikov, Ivan V. Smirnov, Alexey A. Belogurov, Yuri P. Rubtsov, Alexey V. Stepanov, Hongkai Zhang, Alexander G. Gabibov, Sergey M. Deyev
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Subjects:
Antiviral peptide
Half-life extension
Pharmacokinetics
Virus neutralizing peptides (VNPs)
Barnase
SARS-CoV-2
Online Access:https://doi.org/10.1038/s41598-025-12444-2
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Virus-neutralizing peptides (VNPs) emerged as promising antiviral drug candidates with unprecedented specificity and cost-effectiveness during the recent COVID-19 pandemic. However, limited avidity, lack of effector functions, short circulatory half-life, and restricted administration routes make them inferior compared to neutralizing antibodies. To address these constraints, a potent VNP that targets the SARS-CoV-2 S protein is combined with Barnase, a highly active RNA-cleaving enzyme from Bacillus amyloliquefaciens. The resulting LCB1-Barnase (LCB1-Bn) chimera retains strong binding affinity for the SARS-CoV-2 S protein and demonstrates a fourfold reduction in IC50 compared to the LCB1 peptide alone in competitive ELISA and in in vitro neutralization tests. In transgenic CAG-hACE2 mice infected with wild-type SARS-CoV-2, intranasal administration of LCB1-Bn significantly improves survival and reduces viral load by 29-fold. To extend circulation life and allow systemic intravenous administration, an albumin-binding domain (ABD) from Streptococcus protein G is added to LCB1-Bn, producing LCB1-ABD-Bn fusion protein which displays a 95-fold increase in serum half-life. LCB1-ABD-Bn exhibits good tolerability at doses below 10 mg/kg and provides protection of SARS-CoV-2-infected CAG-hACE2 animals in 24-hour post-infection intraperitoneal treatment. Cryo-EM reveals the LCB1-ABD-Bn’s tight interaction with S protein RBD domains, highlighting its potential as a promising drug candidate against SARS-CoV-2.
ISSN:2045-2322

Similar Items