tetano
Editor, Senior Moderator
Antiviral Res
. 2023 Jul 10;105669.
doi: 10.1016/j.antiviral.2023.105669. Online ahead of print. Evaluating Z-FA-FMK, a host cathepsin L protease inhibitor, as a potent and broad-spectrum antiviral therapy against SARS-CoV-2 and related coronaviruses
Ju Hwan Jeong[SUP] 1 [/SUP], Jang-Hoon Choi[SUP] 2 [/SUP], Beom Kyu Kim[SUP] 1 [/SUP], Seong Cheol Min[SUP] 1 [/SUP], Santosh Chokkakula[SUP] 1 [/SUP], Sol Oh[SUP] 1 [/SUP], Ji-Hyun Park[SUP] 1 [/SUP], Sang-Mu Shim[SUP] 2 [/SUP], Eung-Gook Kim[SUP] 3 [/SUP], Young Ki Choi[SUP] 4 [/SUP], Joo-Yeon Lee[SUP] 5 [/SUP], Yun Hee Baek[SUP] 6 [/SUP], Min-Suk Song[SUP] 7 [/SUP]
Affiliations
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 EC[SUB]50[/SUB] 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.
Keywords: Host-targeting antiviral; In vitro; K18 hACE2 transgenic mouse; SARS-CoV-2; Z-FA-FMK
. 2023 Jul 10;105669.
doi: 10.1016/j.antiviral.2023.105669. Online ahead of print. Evaluating Z-FA-FMK, a host cathepsin L protease inhibitor, as a potent and broad-spectrum antiviral therapy against SARS-CoV-2 and related coronaviruses
Ju Hwan Jeong[SUP] 1 [/SUP], Jang-Hoon Choi[SUP] 2 [/SUP], Beom Kyu Kim[SUP] 1 [/SUP], Seong Cheol Min[SUP] 1 [/SUP], Santosh Chokkakula[SUP] 1 [/SUP], Sol Oh[SUP] 1 [/SUP], Ji-Hyun Park[SUP] 1 [/SUP], Sang-Mu Shim[SUP] 2 [/SUP], Eung-Gook Kim[SUP] 3 [/SUP], Young Ki Choi[SUP] 4 [/SUP], Joo-Yeon Lee[SUP] 5 [/SUP], Yun Hee Baek[SUP] 6 [/SUP], Min-Suk Song[SUP] 7 [/SUP]
Affiliations
- PMID: 37437781
- DOI: 10.1016/j.antiviral.2023.105669
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 EC[SUB]50[/SUB] 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.
Keywords: Host-targeting antiviral; In vitro; K18 hACE2 transgenic mouse; SARS-CoV-2; Z-FA-FMK