Identification of Pan-Coronavirus Neutralizing Aptamers Through CRISmers Targeting the Conserved Fusion Peptide

Ju Zhang1,2,3, Airu Zhu4, Shixian Wei1,2,3,5

  • 1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

PubMed

Insights

Researchers developed a new aptamer using the CRISmers system to target the conserved fusion peptide of SARS-CoV-2. This pan-coronavirus aptamer shows broad neutralization activity against multiple variants and other coronaviruses.

Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • The emergence of coronavirus outbreaks necessitates the development of broad-spectrum antiviral therapeutics.
  • The Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated proteins (CRISPR/Cas)-mediated CRISmers platform facilitates RNA aptamer identification.

Purpose of the Study:

  • To apply the CRISmers system for identifying pan-coronavirus RNA aptamers targeting the conserved fusion peptide (FP) of SARS-CoV-2.
  • To evaluate the therapeutic potential of identified aptamers against SARS-CoV-2 and other coronaviruses.

Main Methods:

  • Utilized the CRISmers cellular screening platform with E.coli as the host system.
  • Targeted the highly conserved fusion peptide (FP) region of SARS-CoV-2.
  • Screened for RNA aptamers with neutralization capabilities.

Main Results:

  • Identified a lead aptamer, designated #FP-10.
  • #FP-10 demonstrated potent pan-coronavirus neutralization activity.
  • Activity was confirmed against multiple SARS-CoV-2 variants and alphacoronaviruses (HCoV-229E, HCoV-NL63).

Conclusions:

  • The identified aptamer #FP-10 exhibits broad-spectrum antiviral activity against clinically relevant coronaviruses.
  • This aptamer holds significant potential for development into a pan-coronavirus therapeutic candidate.
  • The CRISmers platform is effective for discovering novel antiviral aptamers.