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
M3 - Article
C2 - 39955340
VL - 15
JO - Scientific Reports
JF - Scientific Reports
IS - 1
ER -