Literature DB >> 33451132

Systematic Search for SARS-CoV-2 Main Protease Inhibitors for Drug Repurposing: Ethacrynic Acid as a Potential Drug.

Camilla Isgrò1,2, Anna Maria Sardanelli1,2, Luigi Leonardo Palese1.   

Abstract

In 2019 an outbreak occurred which resulted in a global pandemic. The causative agent has been identified in a virus belonging to theCoronaviridae family, similar to the agent of SARS, referred to as SARS-CoV-2. This epidemic spread rapidly globally with high morbidity and mortality. Although vaccine development is at a very advanced stage, there are currently no truly effective antiviral drugs to treat SARS-CoV-2 infection. In this study we present systematic and integrative antiviral drug repurposing effort aimed at identifying, among the drugs already authorized for clinical use, some active inhibitors of the SARS-CoV-2 main protease. The most important result of this analysis is the demonstration that ethacrynic acid, a powerful diuretic, is revealed to be an effective inhibitor of SARS-CoV-2 main protease. Even with all the necessary cautions, given the particular nature of this drug, these data can be the starting point for the development of an effective therapeutic strategy against SARS-CoV-2.

Entities:  

Keywords:  3C-like protease; 3CL protease; COVID-19; Mpro; SARS-CoV-2; coronavirus; drug repurposing; main protease; protease inhibitors

Mesh:

Substances:

Year:  2021        PMID: 33451132      PMCID: PMC7828626          DOI: 10.3390/v13010106

Source DB:  PubMed          Journal:  Viruses        ISSN: 1999-4915            Impact factor:   5.048


  56 in total

1.  The clinical pharmacology of ethacrynic acid.

Authors:  Janos Molnar; John C Somberg
Journal:  Am J Ther       Date:  2009 Jan-Feb       Impact factor: 2.688

2.  Structure of the main protease from a global infectious human coronavirus, HCoV-HKU1.

Authors:  Qi Zhao; Shuang Li; Fei Xue; Yilong Zou; Cheng Chen; Mark Bartlam; Zihe Rao
Journal:  J Virol       Date:  2008-06-18       Impact factor: 5.103

3.  In Silico Insights into the SARS CoV-2 Main Protease Suggest NADH Endogenous Defences in the Control of the Pandemic Coronavirus Infection.

Authors:  Annamaria Martorana; Carla Gentile; Antonino Lauria
Journal:  Viruses       Date:  2020-07-26       Impact factor: 5.048

4.  Structural and Evolutionary Analysis Indicate That the SARS-CoV-2 Mpro Is a Challenging Target for Small-Molecule Inhibitor Design.

Authors:  Maria Bzówka; Karolina Mitusińska; Agata Raczyńska; Aleksandra Samol; Jack A Tuszyński; Artur Góra
Journal:  Int J Mol Sci       Date:  2020-04-28       Impact factor: 5.923

5.  Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease.

Authors:  Lifeng Fu; Fei Ye; Yong Feng; Feng Yu; Qisheng Wang; Yan Wu; Cheng Zhao; Huan Sun; Baoying Huang; Peihua Niu; Hao Song; Yi Shi; Xuebing Li; Wenjie Tan; Jianxun Qi; George Fu Gao
Journal:  Nat Commun       Date:  2020-09-04       Impact factor: 17.694

6.  Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain.

Authors:  Kanchan Anand; Gottfried J Palm; Jeroen R Mesters; Stuart G Siddell; John Ziebuhr; Rolf Hilgenfeld
Journal:  EMBO J       Date:  2002-07-01       Impact factor: 11.598

7.  PubChem 2019 update: improved access to chemical data.

Authors:  Sunghwan Kim; Jie Chen; Tiejun Cheng; Asta Gindulyte; Jia He; Siqian He; Qingliang Li; Benjamin A Shoemaker; Paul A Thiessen; Bo Yu; Leonid Zaslavsky; Jian Zhang; Evan E Bolton
Journal:  Nucleic Acids Res       Date:  2019-01-08       Impact factor: 16.971

8.  Structural basis of mercury- and zinc-conjugated complexes as SARS-CoV 3C-like protease inhibitors.

Authors:  Cheng-Chung Lee; Chih-Jung Kuo; Min-Feng Hsu; Po-Huang Liang; Jim-Min Fang; Jiun-Jie Shie; Andrew H-J Wang
Journal:  FEBS Lett       Date:  2007-11-05       Impact factor: 4.124

9.  A mechanistic view of enzyme inhibition and peptide hydrolysis in the active site of the SARS-CoV 3C-like peptidase.

Authors:  Jiang Yin; Chunying Niu; Maia M Cherney; Jianmin Zhang; Carly Huitema; Lindsay D Eltis; John C Vederas; Michael N G James
Journal:  J Mol Biol       Date:  2007-06-08       Impact factor: 5.469

10.  Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication.

Authors:  Wayne Vuong; Muhammad Bashir Khan; Conrad Fischer; Elena Arutyunova; Tess Lamer; Justin Shields; Holly A Saffran; Ryan T McKay; Marco J van Belkum; Michael A Joyce; Howard S Young; D Lorne Tyrrell; John C Vederas; M Joanne Lemieux
Journal:  Nat Commun       Date:  2020-08-27       Impact factor: 17.694

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  2 in total

Review 1.  Therapeutic dilemmas in addressing SARS-CoV-2 infection: Favipiravir versus Remdesivir.

Authors:  Paul Andrei Negru; Andrei-Flavius Radu; Cosmin Mihai Vesa; Tapan Behl; Mohamed M Abdel-Daim; Aurelia Cristina Nechifor; Laura Endres; Manuela Stoicescu; Bianca Pasca; Delia Mirela Tit; Simona Gabriela Bungau
Journal:  Biomed Pharmacother       Date:  2022-02-04       Impact factor: 6.529

2.  SARS-CoV-2 Main Protease Active Site Ligands in the Human Metabolome.

Authors:  Anna Maria Sardanelli; Camilla Isgrò; Luigi Leonardo Palese
Journal:  Molecules       Date:  2021-03-05       Impact factor: 4.411

  2 in total

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