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May 8, 2026Open Access

Synthesis and biological evaluation of modified peptide derivatives targeting the SARS-CoV-2 nsp3 macrodomain (Mac1) replication domain

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Authors

ÖÖÖzge ÖzmenBOBetül OruçoğluSBSerap İpek Dingiş Birgül

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Overview

Modified peptide derivatives exhibit varying inhibition of viral replication in a SARS-CoV-2 replicon system, indicating potential for therapy.

Key Points

  • This research aims to evaluate modified peptide derivatives for their ability to inhibit SARS-CoV-2 replication by targeting the nsp3 macrodomain.
  • Designed and synthesized modified peptide derivatives (D1−D15) with specific amino acid compositions.
  • Evaluated cytotoxicity of compounds in healthy cell lines (CCD1079Sk).
  • Performed bioactivity assays using a SARS-CoV-2 replicon system to determine inhibitory activity against viral replication.
  • Compound D15 shows the highest inhibition of viral replication with an IC50 of 22.2 μM (95% CI: 15.4−35.7 μM).
  • Compound D14 demonstrates moderate inhibition with an IC50 of 61.2 μM (95% CI: 39.2−143.9 μM).
  • Compounds with a histidine side chain exhibit higher biological activity, indicating a potential structure−activity relationship.

Cite This Study

Özmen et al. (2026) studied this question.

synapsesocial.com/papers/69fd7e79bfa21ec5bbf06be5https://doi.org/10.1021/acsomega.6c02033?src=getftr&utm_source=clarivate&getft_integrator=clarivate
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