2. Academic Validation
  3. Inhibition of SARS-CoV-2 Infection by Human Defensin HNP1 and Retrocyclin RC-101

Inhibition of SARS-CoV-2 Infection by Human Defensin HNP1 and Retrocyclin RC-101

  • J Mol Biol. 2022 Mar 30;434(6):167225. doi: 10.1016/j.jmb.2021.167225.
Elena Kudryashova 1,  Ashley Zani 2,  Geraldine Vilmen 3,  Amit Sharma 4,  Wuyuan Lu 5,  Jacob S Yount 6,  Dmitri S Kudryashov 7
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA; Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA.
  • 2 Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
  • 3 Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
  • 4 Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA. Electronic address: https://twitter.com/ConradoPedebos.
  • 5 Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Science, and Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai 200032, China.
  • 6 Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210, USA. Electronic address: https://twitter.com/ConradoPedebos.
  • 7 Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA; Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA. Electronic address: https://twitter.com/ConradoPedebos.
PMID: 34487793 DOI: 10.1016/j.jmb.2021.167225
Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is an enveloped virus responsible for the COVID-19 pandemic. The emergence of new potentially more transmissible and vaccine-resistant variants of SARS-CoV-2 is an ever-present threat. Thus, it remains essential to better understand innate immune mechanisms that can inhibit the virus. One component of the innate immune system with broad antipathogen, including Antiviral, activity is a group of cationic immune peptides termed defensins. The ability of defensins to neutralize enveloped and non-enveloped viruses and to inactivate numerous Bacterial toxins correlate with their ability to promote the unfolding of proteins with high conformational plasticity. We found that human neutrophil α-defensin HNP1 binds to SARS-CoV-2 Spike protein with submicromolar affinity that is more than 20 fold stronger than its binding to serum albumin. As such, HNP1, as well as a θ-defensin retrocyclin RC-101, both interfere with Spike-mediated membrane fusion, Spike-pseudotyped lentivirus Infection, and authentic SARS-CoV-2 Infection in Cell Culture. These effects correlate with the abilities of the defensins to destabilize and precipitate Spike protein and inhibit the interaction of Spike with the ACE2 receptor. Serum reduces the anti-SARS-CoV-2 activity of HNP1, though at high concentrations, HNP1 was able to inactivate the virus even in the presence of serum. Overall, our results suggest that defensins can negatively affect the native conformation of SARS-CoV-2 Spike, and that α- and θ-defensins may be valuable tools in developing SARS-CoV-2 Infection prevention strategies.

Keywords

SARS-CoV-2; defensins; human neutrophil peptide HNP1; innate immunity; retrocyclin RC-101.

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