9-aminominocycline potentiates the efficacy of EIDD-1931 and PF-332 by targeting the papain like protease enzyme of SARS-CoV-2.

Kabita Pandey; Devin Shane M Lewis; Kyeongin Heo; Arpan Acharya; Travis Fields; Kritika Gowda; George Dean; Srujana Rayalam; Siddappa N Byrareddy; Vicky Mody; Shashidharamurthy Taval

doi:10.1038/s41598-025-89717-3

9-aminominocycline potentiates the efficacy of EIDD-1931 and PF-332 by targeting the papain like protease enzyme of SARS-CoV-2.

Kabita Pandey
, Devin Shane M Lewis
, Kyeongin Heo
, Arpan Acharya
, Travis Fields
, Kritika Gowda
, George Dean
, Srujana Rayalam
, Siddappa N Byrareddy
, Vicky Mody
, Shashidharamurthy Taval

Research output: Contribution to journal › Article › peer-review

Abstract

The 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp) are key enzymes in SARS-CoV-2 replication and serve as critical targets for an antiviral drug. Currently, Paxlovid® and Lagevrio™ specifically target 3CLpro and RdRp, respectively, for COVID-19 treatment. However, no antivirals target for the SARS-CoV-2 PLpro enzyme, essential for viral replication and suppression of the host antiviral immune response. This study identified 9-aminominocycline (9-AMN) as a potent inhibitor of SARS-CoV-2 PLpro. Unlike the parent compound minocycline, 9-AMN inhibits PLpro's proteolytic and deubiquitinase activities by approximately 90%, with IC

Original language	American English
Journal	Scientific Reports
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41598-025-89717-3
State	Published - Feb 15 2025

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9-aminominocycline potentiates the efficacy of EIDD-1931 and PF-3Final published version, 3.16 MBLicense: CC BY-NC-ND

http://digitalcommons.pcom.edu/scholarly_papers/2304

Cite this

@article{118d4d93204642eca4164c7762df748e,

title = "9-aminominocycline potentiates the efficacy of EIDD-1931 and PF-332 by targeting the papain like protease enzyme of SARS-CoV-2.",

abstract = "The 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp) are key enzymes in SARS-CoV-2 replication and serve as critical targets for an antiviral drug. Currently, Paxlovid{\textregistered} and Lagevrio{\texttrademark} specifically target 3CLpro and RdRp, respectively, for COVID-19 treatment. However, no antivirals target for the SARS-CoV-2 PLpro enzyme, essential for viral replication and suppression of the host antiviral immune response. This study identified 9-aminominocycline (9-AMN) as a potent inhibitor of SARS-CoV-2 PLpro. Unlike the parent compound minocycline, 9-AMN inhibits PLpro's proteolytic and deubiquitinase activities by approximately 90\%, with IC",

author = "Kabita Pandey and Lewis, \{Devin Shane M\} and Kyeongin Heo and Arpan Acharya and Travis Fields and Kritika Gowda and George Dean and Srujana Rayalam and Byrareddy, \{Siddappa N\} and Vicky Mody and Shashidharamurthy Taval",

year = "2025",

month = feb,

day = "15",

doi = "10.1038/s41598-025-89717-3",

language = "American English",

volume = "15",

journal = "Scientific Reports",

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}

TY - JOUR

T1 - 9-aminominocycline potentiates the efficacy of EIDD-1931 and PF-332 by targeting the papain like protease enzyme of SARS-CoV-2.

AU - Pandey, Kabita

AU - Lewis, Devin Shane M

AU - Heo, Kyeongin

AU - Acharya, Arpan

AU - Fields, Travis

AU - Gowda, Kritika

AU - Dean, George

AU - Rayalam, Srujana

AU - Byrareddy, Siddappa N

AU - Mody, Vicky

AU - Taval, Shashidharamurthy

PY - 2025/2/15

Y1 - 2025/2/15

N2 - The 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp) are key enzymes in SARS-CoV-2 replication and serve as critical targets for an antiviral drug. Currently, Paxlovid® and Lagevrio™ specifically target 3CLpro and RdRp, respectively, for COVID-19 treatment. However, no antivirals target for the SARS-CoV-2 PLpro enzyme, essential for viral replication and suppression of the host antiviral immune response. This study identified 9-aminominocycline (9-AMN) as a potent inhibitor of SARS-CoV-2 PLpro. Unlike the parent compound minocycline, 9-AMN inhibits PLpro's proteolytic and deubiquitinase activities by approximately 90%, with IC

AB - The 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp) are key enzymes in SARS-CoV-2 replication and serve as critical targets for an antiviral drug. Currently, Paxlovid® and Lagevrio™ specifically target 3CLpro and RdRp, respectively, for COVID-19 treatment. However, no antivirals target for the SARS-CoV-2 PLpro enzyme, essential for viral replication and suppression of the host antiviral immune response. This study identified 9-aminominocycline (9-AMN) as a potent inhibitor of SARS-CoV-2 PLpro. Unlike the parent compound minocycline, 9-AMN inhibits PLpro's proteolytic and deubiquitinase activities by approximately 90%, with IC

U2 - 10.1038/s41598-025-89717-3

DO - 10.1038/s41598-025-89717-3

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