Literature DB >> 32275393

Accelerated Discovery of Potent Fusion Inhibitors for Respiratory Syncytial Virus.

Nicole Pribut1, Thomas M Kaiser1, Robert J Wilson1, Edgars Jecs1, Zackery W Dentmon1, Stephen C Pelly1, Savita Sharma1, Perry W Bartsch1, Pieter B Burger1, Soyon S Hwang1, Thalia Le1, Julien Sourimant2, Jeong-Joong Yoon2, Richard K Plemper2, Dennis C Liotta1.   

Abstract

A series of five benzimidazole-based compounds were identified using a machine learning algorithm as potential inhibitors of the respiratory syncytial virus (RSV) fusion protein. These compounds were synthesized, and compound 2 in particular exhibited excellent in vitro potency with an EC50 value of 5 nM. This new scaffold was then further refined leading to the identification of compound 44, which exhibited a 10-fold improvement in activity with an EC50 value of 0.5 nM.

Entities:  

Keywords:  RSV; benzimidazole; fusion inhibitor; machine learning

Mesh：

Substances：

Year:  2020        PMID： 32275393      PMCID： PMC7456560          DOI： 10.1021/acsinfecdis.9b00524

Source DB:  PubMed          Journal:  ACS Infect Dis        ISSN： 2373-8227            Impact factor:   5.084


  32 in total

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4.  Molecular mechanism of respiratory syncytial virus fusion inhibitors.

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Journal:  Nat Chem Biol       Date:  2015-12-07       Impact factor: 15.040

5.  Activity, assay and target data curation and quality in the ChEMBL database.

Authors:  George Papadatos; Anna Gaulton; Anne Hersey; John P Overington
Journal:  J Comput Aided Mol Des       Date:  2015-07-23       Impact factor: 3.686

6.  Challenges and opportunities in developing respiratory syncytial virus therapeutics.

Authors:  Eric A F Simões; John P DeVincenzo; Michael Boeckh; Louis Bont; James E Crowe; Paul Griffiths; Frederick G Hayden; Richard L Hodinka; Rosalind L Smyth; Keith Spencer; Steffen Thirstrup; Edward E Walsh; Richard J Whitley
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7.  Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series.

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8.  Error Tolerance of Machine Learning Algorithms across Contemporary Biological Targets.

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Review 9.  Respiratory syncytial virus: current and emerging treatment options.

Authors:  Tiffany L Turner; Benjamin T Kopp; Grace Paul; Lindsay C Landgrave; Don Hayes; Rohan Thompson
Journal:  Clinicoecon Outcomes Res       Date:  2014-04-25

10.  Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor.

Authors:  Dirk Roymans; Sarhad S Alnajjar; Michael B Battles; Panchan Sitthicharoenchai; Polina Furmanova-Hollenstein; Peter Rigaux; Joke Van den Berg; Leen Kwanten; Marcia Van Ginderen; Nick Verheyen; Luc Vranckx; Steffen Jaensch; Eric Arnoult; Richard Voorzaat; Jack M Gallup; Alejandro Larios-Mora; Marjolein Crabbe; Dymphy Huntjens; Pierre Raboisson; Johannes P Langedijk; Mark R Ackermann; Jason S McLellan; Sandrine Vendeville; Anil Koul
Journal:  Nat Commun       Date:  2017-08-01       Impact factor: 14.919
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  1 in total

1.  Probing In Silico the Benzimidazole Privileged Scaffold for the Development of Drug-like Anti-RSV Agents.

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Journal:  Pharmaceuticals (Basel)       Date:  2021-12-15
  1 in total

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