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Updated: Jan 7, 2026

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Targeting SARS-CoV-2 Mpro and PLpro by Repurposing Clinically Approved Drugs.

Qiaoyu Fang1, Meng Lu1, Derong Chen1

  • 1Shenzhen Center for Chronic Disease Control and Prevention, Shenzhen Institute of Dermatology, Shenzhen 518020, China.

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|December 31, 2025
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Summary
This summary is machine-generated.

Two existing drugs, oxytocin and risedronate sodium, show potential for treating SARS-CoV-2 infections by inhibiting key viral proteases (Mpro and PLpro), thus slowing virus replication.

Keywords:
MproPLproSARS-CoV-2cephalosporin drugsoxytocin

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Area of Science:

  • Virology
  • Drug Discovery
  • Biochemistry

Background:

  • SARS-CoV-2 proteases, papain-like protease (PLpro) and main protease (Mpro), are crucial for viral replication and pathogenesis.
  • These proteases are conserved targets for antiviral therapies.
  • Viral activity contributes to immune suppression and inflammation.

Purpose of the Study:

  • To identify potential inhibitors of SARS-CoV-2 Mpro and PLpro through drug repurposing.
  • To evaluate the antiviral efficacy of identified compounds against SARS-CoV-2.
  • To explore novel therapeutic strategies for COVID-19.

Main Methods:

  • Small-molecule chip screening.
  • Enzymatic assays for protease activity.
  • SARS-CoV-2 spike pseudotyped virus detection.
  • Molecular docking simulations.

Main Results:

  • Oxytocin and risedronate sodium were identified as potential Mpro and PLpro inhibitors.
  • These compounds demonstrated an influence on protease activity, inhibiting viral replication.
  • The findings suggest a role for these repurposed drugs in managing SARS-CoV-2 infection.

Conclusions:

  • Oxytocin and risedronate sodium show promise for repurposing in COVID-19 treatment.
  • Inhibition of Mpro and PLpro by these molecules may alleviate SARS-CoV-2 infection.
  • Cephalosporins may also be considered for expanding the antiviral drug library.