Ciclesonide Inhibits SARS-CoV-2 Papain-Like Protease in Vitro

• Published in: Biological & pharmaceutical bulletin Vol. 47; no. 5; pp. 965 - 966
• Main Authors: Kiba, Yuka, Tanikawa, Takashi, Kitamura, Masashi
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 17.05.2024; Japan Science and Technology Agency
• Subjects: Antiviral Agents - pharmacology; ciclesonide; Coronavirus 3C Proteases - antagonists & inhibitors; Coronavirus 3C Proteases - metabolism; coronavirus disease 2019 (COVID-19); Coronavirus Papain-Like Proteases - antagonists & inhibitors; Coronavirus Papain-Like Proteases - metabolism; Coronaviruses; COVID-19; COVID-19 - virology; COVID-19 Drug Treatment; Enzymatic activity; Glucocorticoids - pharmacology; Humans; Immune response; Molecular Docking Simulation; Papain; papain-like protease (PLpro); Pregnenediones - pharmacology; SARS-CoV-2 - drug effects; Severe acute respiratory syndrome coronavirus 2; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Therapeutic targets; Ubiquitin; papain-like protease (PLpro); ciclesonide; coronavirus disease 2019 (COVID-19); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b24-00038

The emergence of coronavirus disease 2019 (COVID-19), a novel identified pneumonia resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has significantly impacted and posed significant challenges to human society. The papain-like protease (PLpro) found in the nonstructural protein 3 of SARS-CoV-2 plays a vital role in viral replication. Moreover, PLpro disrupts the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 from host proteins. Consequently, PLpro has emerged as a promising drug target against SARS-CoV-2 infection. Computational studies have reported that ciclesonide can bind to SARS-CoV-2 PLpro. However, the inhibitory effects of ciclenoside on the PLpro have not been experimentally evaluated. Here, we evaluated the inhibitory effects of synthetic glucocorticoids (sGCs), including ciclesonide, on SARS-CoV-2 PLpro in vitro assay. Ciclesonide significantly inhibited the enzymatic activity of PLpro, compared with other sGCs and its IC50 was 18.4 ± 1.89 µM. These findings provide insights into the development of PLpro inhibitors.