Tuftsin: A Natural Molecule Against SARS-CoV-2 Infection

Jiahao Huang1, Jing Wang2, Yan Li1

  • 1Department of Immunology, School of Basic Medical Sciences, Peking University. NHC Key Laboratory of Medical Immunology(Peking University), Beijing, China.

Insights

Tuftsin, a peptide targeting ACE2 and NRP1 receptors, effectively blocks SARS-CoV-2 S1 protein binding, suggesting its potential as a COVID-19 therapeutic agent.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Coronavirus disease 2019 (COVID-19) remains a global health challenge, necessitating novel therapeutic strategies.
  • Neuropilin 1 (NRP1) is identified as a key receptor facilitating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry.
  • Tuftsin, a natural peptide derived from immunoglobulin G (IgG), has potential immunomodulatory functions.

Purpose of the Study:

  • To investigate the potential of tuftsin as a therapeutic agent against COVID-19.
  • To explore the interaction of tuftsin with ACE2 and NRP1 receptors, key players in SARS-CoV-2 infection.
  • To determine if tuftsin can inhibit the binding of SARS-CoV-2 to host cell receptors.

Main Methods:

  • Gene overlap analysis between tuftsin targets and COVID-19-associated genes.
  • Molecular docking simulations to predict binding interactions between tuftsin, ACE2, and NRP1.
  • Surface Plasmon Resonance (SPR) analysis to confirm direct binding of tuftsin to ACE2 and NRP1.
  • SPR-based competition assays to evaluate tuftsin's ability to block SARS-CoV-2 S1 protein binding.

Main Results:

  • Identified 91 overlapping genes between tuftsin targets and COVID-19-associated genes.
  • Demonstrated that tuftsin targets both ACE2 and NRP1, with binding sites overlapping with SARS-CoV-2 S1 protein interaction regions.
  • Confirmed direct binding of tuftsin to ACE2 and NRP1 using SPR.
  • Showcased tuftsin's efficacy in preventing SARS-CoV-2 S1 protein binding to ACE2 in competition assays.

Conclusions:

  • Tuftsin exhibits direct binding to ACE2 and NRP1, key receptors for SARS-CoV-2.
  • Tuftsin effectively inhibits the interaction between SARS-CoV-2 S1 protein and ACE2.
  • Tuftsin presents a promising therapeutic candidate for COVID-19, warranting further clinical investigation.