Potential clinical drugs as covalent inhibitors of the priming proteases of the spike protein of SARS-CoV-2

Li, Qizhang; Wang, Zhiying; Zheng, Qiang; Liu, Sen

doi:10.1016/j.csbj.2020.08.016

Cited by 20 publications

(8 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The three-dimensional structure coordinates of all the targets were retrieved from Protein Data Bank (PDB) except TMPRSS2. The homology model of TMPRSS2 was downloaded from the SARS-CoV-2 repository of SWISS-MODEL [ 36 ]. The structure was built using serine protease hepsin as a template and showed Q Mean score is -1.62 for the modeled structure.…”

Section: Methodsmentioning

confidence: 99%

Setomimycin as a potential molecule for COVID‑19 target: in silico approach and in vitro validation

et al. 2022

View full text Add to dashboard Cite

COVID-19 pandemic caused by the SARS-CoV-2 virus has led to a worldwide crisis. In view of emerging variants time to time, there is a pressing need of effective COVID-19 therapeutics. Setomimycin, a rare tetrahydroanthracene antibiotic, remained unexplored for its therapeutic uses. Herein, we report our investigations on the potential of setomimycin as COVID-19 therapeutic. Pure setomimycin was isolated from Streptomyces sp. strain RA-WS2 from NW Himalayan region followed by establishing in silico as well as in vitro anti-SARS-CoV-2 property of the compound against SARS-CoV-2 main protease (M pro ). It was found that the compound targets M pro enzyme with an IC 50 value of 12.02 ± 0.046 μM. The molecular docking study revealed that the compound targets Glu166 residue of M pro enzyme, hence preventing dimerization of SARS-CoV-2 M pro monomer. Additionally, the compound also exhibited anti-inflammatory and anti-oxidant property, suggesting that setomimycin may be a viable option for application against COVID-19 infections. Graphical abstract

show abstract

Section: Methodsmentioning

confidence: 99%

Setomimycin as a potential molecule for COVID‑19 target: in silico approach and in vitro validation

et al. 2022

View full text Add to dashboard Cite

show abstract

“…ii) Targeting host proteins provides another way to fight SARS-CoV-2. Li et al developed covalent inhibitors using the SCAR tool for TMPRSS2 (see introduction) and CatB/L, which prime the S protein together with TMPRSS2 [73] .…”

Section: Structure-based Computational Techniquesmentioning

confidence: 99%

Recent computational drug repositioning strategies against SARS-CoV-2

Qin

Chen

et al. 2022

Computational and Structural Biotechnology Journal

View full text Add to dashboard Cite

“…The study identified five potential inhibitors of CatB that are neratinib, [Z]-dacomitinib, trapoxin B, HKI-357, and domatinostat and four TMPRSS2 potential inhibitors including [S]-boceprevir, [R]-boceprevir, aceneuramic acid, and lodoxamide. Moreover, trapoxin B (Kijima et al 1993 ), HKI-357 (Tsou et al 2005 ), neratinib (Tsou et al 2005 ), [Z]-dacomitinib (Garuti et al 2011 ) and boceprevir (Nazario de Moraes et al 2019 ) have already proven to be covalent inhibitors (Li and Wang 2020 ). Some other potential spike protein inhibitors (Table 1 ) are given in details as follows:…”

Section: Potential Covalent Spike Protein Inhibitorsmentioning

confidence: 99%

“…Dacomitinib, as a potent EGFR TKI irreversibly binds to the receptors and exhibits a strong cellular potency against EGFR oncogenic variants (Deeks and Keating 2018 ). In silico screening of dacomitinib in addition to neratinib and domatinostat as a cathepsin-binding drug that targets viral and host, proteins have also been reported (Li et al 2020 ).…”

Section: Potential Covalent Spike Protein Inhibitorsmentioning

confidence: 99%

Therapeutically effective covalent spike protein inhibitors in treatment of SARS-CoV-2

et al. 2021

View full text Add to dashboard Cite

COVID-19 [coronavirus disease 2019] has resulted in over 204,644,849 confirmed cases and over 4,323,139 deaths throughout the world as of 12 August 2021, a total of 4,428,168,759 vaccine doses have been administered. The lack of potentially effective drugs against the virus is making the situation worse and dangerous. Numerous forces are working on finding an effective treatment against the virus but it is believed that a de novo drug would take several months even if huge financial support is provided. The only solution left with is drug repurposing that would not only provide effective therapy with the already used clinical drugs, but also save time and cost of the de novo drug discovery. The initiation of the COVID-19 infection starts with the attachment of spike glycoprotein of SARS-CoV-2 to the host receptor. Hence, the inhibition of the binding of the virus to the host membrane and the entry of the viral particle into the host cell are one of the main therapeutic targets. This paper not only summarizes the structure and the mechanism of spike protein, but the main focus is on the potential covalent spike protein inhibitors.

show abstract

Potential clinical drugs as covalent inhibitors of the priming proteases of the spike protein of SARS-CoV-2

Abstract: Graphical abstract

Cited by 20 publications

References 40 publications

Setomimycin as a potential molecule for COVID‑19 target: in silico approach and in vitro validation

Setomimycin as a potential molecule for COVID‑19 target: in silico approach and in vitro validation

Recent computational drug repositioning strategies against SARS-CoV-2

Therapeutically effective covalent spike protein inhibitors in treatment of SARS-CoV-2

Contact Info

Product

Resources

About