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Screening-Identified Oxazole-4-Carboxamide KB-2777 Exhibits In Vitro Anti-Coronavirus Activity.

Bud Jung1, Woonsung Na2, Minjoo Yeom3

  • 1Department of Pharmacy, College of Pharmacy, Korea University, Sejong 30019, Republic of Korea.

Pharmaceutics
|November 27, 2025
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Summary

The novel antiviral KB-2777 demonstrates broad in vitro activity against alpha and beta coronaviruses, including SARS-CoV-2 variants. It shows promising additive to synergistic effects when combined with existing direct-acting antivirals (DAAs).

Keywords:
HCoV-NL63HCoV-OC43PEDVcombination therapyoxazole-4-carboxamidetime-of-addition

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Area of Science:

  • Virology
  • Drug Discovery
  • Immunology

Background:

  • Direct-acting antivirals (DAAs) exhibit lineage-specific activity and are prone to rapid resistance development.
  • The oxazole-4-carboxamide compound KB-2777 was identified as a promising lead for broad-spectrum coronavirus inhibition.

Purpose of the Study:

  • To characterize the in vitro antiviral activity of KB-2777 against alpha and beta coronaviruses.
  • To determine the time-of-addition (TOA) profile and host-response signatures of KB-2777.
  • To evaluate the combinability of KB-2777 with benchmark DAAs.

Main Methods:

  • KB-2777 was tested against HCoV-NL63, HCoV-OC43, and PEDV, quantifying viral RNA, viral load (TCID50), and cytopathic effect (CPE).
  • Time-of-addition experiments assessed inhibition at different treatment timings (pre-, co-, post-infection).
  • Combinations with nirmatrelvir and GS-441524 were evaluated using ZIP scores; host-response transcripts were profiled.

Main Results:

  • KB-2777 exhibited potent antiviral activity with EC50 values ranging from 1.59 to 5.27 μM across tested coronaviruses.
  • The compound demonstrated significant post-treatment activity, with clear inhibition observed 48-72 hours post-infection.
  • Combinations with nirmatrelvir and GS-441524 showed additive to synergistic effects (ZIP scores 5.16 and 8.40, respectively).
  • KB-2777 modulated host-response transcripts, including IL6, IFNB1, and ISG15, in infected cells.

Conclusions:

  • KB-2777 displays reproducible cell-based anti-coronavirus activity across alpha and beta lineages.
  • Its TOA profile suggests early post-entry host modulation mechanisms.
  • KB-2777 is compatible with benchmark DAAs, supporting further development for coronavirus treatment.