Abstract |
Even though the World Health Organization announced the end of the COVID-19 pandemic as a global public health emergency on May 5, 2023, SARS-CoV-2 continues to pose a significant health threat worldwide, resulting in substantial numbers of infections and fatalities. This study investigated the antiviral potential of Z-FA-FMK (FMK), a novel host cathepsin L protease inhibitor, against SARS-CoV-2 infection using both in vitro and in vivo models. In vitro assessments of FMK against a diverse set of SARS-CoV-2 strains, including the Wuhan-like strain and nine variants, demonstrated potent inhibition with EC50 values ranging from 0.55 to 2.41 μM, showcasing similar or superior efficacy compared to FDA-approved antivirals nirmatrelvir (NTV) and molnupiravir (MPV). In vivo experiments using orally administered FMK (25 mg/kg) in SARS-CoV-2-infected K18 hACE2 transgenic mice revealed improved survival rates of 60% and accelerated recovery compared to NTV and MPV treatments. Additionally, FMK displayed a longer half-life (17.26 ± 8.89 h) than NTV and MPV in the mouse model. Due to its host-targeting mechanism, FMK offers potential advantages such as reduced drug resistance and broad-spectrum antiviral activity against multiple coronaviruses. These findings indicate that FMK may serve as a promising candidate for further clinical evaluation in the fight against SARS-CoV-2.
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Authors | Ju Hwan Jeong, Jang-Hoon Choi, Beom Kyu Kim, Seong Cheol Min, Santosh Chokkakula, Sol Oh, Ji-Hyun Park, Sang-Mu Shim, Eung-Gook Kim, Young Ki Choi, Joo-Yeon Lee, Yun Hee Baek, Min-Suk Song |
Journal | Antiviral research
(Antiviral Res)
Vol. 216
Pg. 105669
(08 2023)
ISSN: 1872-9096 [Electronic] Netherlands |
PMID | 37437781
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2023. Published by Elsevier B.V. |
Chemical References |
- Protease Inhibitors
- MDL 201053
- Cathepsin L
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
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Topics |
- Animals
- Mice
- Humans
- Protease Inhibitors
(pharmacology, therapeutic use)
- SARS-CoV-2
- Cathepsin L
- Pandemics
- COVID-19
- Anti-Infective Agents
- Antiviral Agents
(pharmacology, therapeutic use)
- Enzyme Inhibitors
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