Recombinant Rod Domain of Vimentin Reduces SARS-CoV-2 Viral Replication by Blocking Spike Protein-ACE2 Interactions

Authors

Fong Wilson Lam
Cameron August Brown
Shannon Elizabeth Ronca

Publication Date

2-20-2024

Journal

International Journal of Molecular Sciences

DOI

10.3390/ijms25052477

PMID

38473724

PMCID

PMC10931652

PubMedCentral® Posted Date

2-20-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Humans, Mice, Animals, Angiotensin-Converting Enzyme 2, Vimentin, Spike Glycoprotein, Coronavirus, COVID-19 Vaccines, Escherichia coli, Pneumonia, Virus Replication, SARS-CoV-2, COVID-19, vimentin, acute lung injury

Abstract

Although the SARS-CoV-2 vaccination is the primary preventive intervention, there are still few antiviral therapies available, with current drugs decreasing viral replication once the virus is intracellular. Adding novel drugs to target additional points in the viral life cycle is paramount in preventing future pandemics. The purpose of this study was to create and test a novel protein to decrease SARS-CoV-2 replication. We created the recombinant rod domain of vimentin (rhRod) in E. coli and used biolayer interferometry to measure its affinity to the SARS-CoV-2 S1S2 spike protein and the ability to block the SARS-CoV-2–ACE2 interaction. We performed plaque assays to measure rhRod’s effect on SARS-CoV-2 replication in Vero E6 cells. Finally, we measured lung inflammation in SARS-CoV-2-exposed K18-hACE transgenic mice given intranasal and intraperitoneal rhRod. We found that rhRod has a high affinity for the S1S2 protein with a strong ability to block S1S2–ACE2 interactions. The daily addition of rhRod decreased viral replication in Vero E6 cells starting at 48 h at concentrations >1 µM. Finally, SARS-CoV-2-infected mice receiving rhRod had decreased lung inflammation compared to mock-treated animals. Based on our data, rhRod decreases SARS-CoV-2 replication in vitro and lung inflammation in vivo. Future studies will need to evaluate the protective effects of rhRod against additional viral variants and identify the optimal dosing scheme that both prevents viral replication and host lung injury.