tetano
Editor, Senior Moderator
Chembiochem
. 2026 Jan;27(1):e202500733.
doi: 10.1002/cbic.202500733. Selection and Characterization of SARS-CoV-2 Spike Binding Clickmers
Nima Moradzadeh[SUP] 1 [/SUP], Anna Jonczyk[SUP] 1 [/SUP], Anton Schmitz[SUP] 1 [/SUP], Volkmar Fieberg[SUP] 1 [/SUP], Laia Civit[SUP] 2 [/SUP], Julián Valero[SUP] 2 3 [/SUP], Michael Famulok[SUP] 1 [/SUP], Günter Mayer[SUP] 1 4 [/SUP]
Affiliations
Expanding the chemical repertoire of canonical nucleotides is key to unlocking the full functional potential of aptamers for diagnostic use. Herein, click-systematic evolution of ligands by exponential enrichment (SELEX) is employed to generate chemically modified DNA aptamers, termed clickmers, that target the SARS-CoV-2 spike (CoV2-S) glycoprotein. Two independent split-combine selection strategies yield distinct clickmer families functionalized with benzofuran or indole moieties. Lead candidates (BF1 and N2) demonstrate nanomolar affinity for wild-type CoV2-S and maintain binding to multiple variants, including Alpha, Delta, and Mu, as validated by flow cytometry, surface plasmon resonance, and microscale thermophoresis. Structure-function analysis reveals essential click-in positions for both full-length clickmers and a truncated N2 variant, as short as 31 nucleotides, which displays increased binding to the Omicron variant. These results highlight the versatility of the click-SELEX platform and exemplify its successful application to a clinically relevant target, advancing previous developments in the field.
Keywords: Covid‐19; SARS‐CoV‐2 spike protein; aptamers; chemically modified aptamers; clickmers.
. 2026 Jan;27(1):e202500733.
doi: 10.1002/cbic.202500733. Selection and Characterization of SARS-CoV-2 Spike Binding Clickmers
Nima Moradzadeh[SUP] 1 [/SUP], Anna Jonczyk[SUP] 1 [/SUP], Anton Schmitz[SUP] 1 [/SUP], Volkmar Fieberg[SUP] 1 [/SUP], Laia Civit[SUP] 2 [/SUP], Julián Valero[SUP] 2 3 [/SUP], Michael Famulok[SUP] 1 [/SUP], Günter Mayer[SUP] 1 4 [/SUP]
Affiliations
- PMID: 41517950
- PMCID: PMC12789893
- DOI: 10.1002/cbic.202500733
Expanding the chemical repertoire of canonical nucleotides is key to unlocking the full functional potential of aptamers for diagnostic use. Herein, click-systematic evolution of ligands by exponential enrichment (SELEX) is employed to generate chemically modified DNA aptamers, termed clickmers, that target the SARS-CoV-2 spike (CoV2-S) glycoprotein. Two independent split-combine selection strategies yield distinct clickmer families functionalized with benzofuran or indole moieties. Lead candidates (BF1 and N2) demonstrate nanomolar affinity for wild-type CoV2-S and maintain binding to multiple variants, including Alpha, Delta, and Mu, as validated by flow cytometry, surface plasmon resonance, and microscale thermophoresis. Structure-function analysis reveals essential click-in positions for both full-length clickmers and a truncated N2 variant, as short as 31 nucleotides, which displays increased binding to the Omicron variant. These results highlight the versatility of the click-SELEX platform and exemplify its successful application to a clinically relevant target, advancing previous developments in the field.
Keywords: Covid‐19; SARS‐CoV‐2 spike protein; aptamers; chemically modified aptamers; clickmers.