Pharmacology and Toxicology

Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs

1. Charlotte Avet
2. Arturo Mancini
3. Billy Breton
4. Christian Le Gouill
5. Alexander S Hauser
6. Claire Normand
7. Hiroyuki Kobayashi
8. Florence Gross
9. Mireille Hogue
10. Viktoriya Lukasheva
11. Stéphane St-Onge
12. Marilyn Carrier
13. Madeleine Héroux
14. Sandra Morissette
15. Eric B Fauman
16. Jean-Philippe Fortin
17. Stephan Schann
18. Xavier Leroy
19. David E Gloriam
20. Michel Bouvier

• Curated by eLife

  Evaluation Summary:

  A challenge to understanding the physiology and therapeutic potential of G protein-coupled receptors (GPCRs) is to understand the range of their couplings to different G proteins. Avet et al developed of a novel set of biosensors to assess the coupling specificity of 100 therapeutically relevant G protein-coupled receptors (GPCRs) to various G protein isoforms and arrestins. The novel screen and results obtained with reference ligands will have broad use for researchers studying GPCRs, potentially impacting discovery of new physiological pathways, understanding adverse effects of currently marketed therapeutics, and discovery of novel, safer therapeutics.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Common coupling map advances GPCR-G protein selectivity

1. Alexander S Hauser
2. Charlotte Avet
3. Claire Normand
4. Arturo Mancini
5. Asuka Inoue
6. Michel Bouvier
7. David E Gloriam

• Curated by eLife

  Evaluation Summary:

  This study is a meta-analysis of previously reported studies on G protein-coupled receptor (GPCR) coupling to G proteins. Three separate data sets that describe the coupling of members of the superfamily of non-sensory GPCRs (~200 genes) to the large family of G protein alpha subunits (~20 genes). The authors try to arrive at a consensus for receptor-G protein coupling from the three data sets, as well as identify and highlight differences or incongruencies. Compiling these vast data sets into a unified format will be extremely useful for investigators to understand receptor and effector relationships. The meta-analysis will help to deconvolute the complex physiology and pharmacology underlying hormone or drug actions acting on receptor superfamilies.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

In vitro effect of a non-immunosuppressive FKBP ligand, FK1706, on SARS-CoV-2 replication in combination with antivirals

1. William E. Fitzsimmons
2. Tracy L. Hartman
3. Michelle Mendenhall
4. Catherine Z. Chen

Reviewed by ScreenIT

Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, A Potential Oral Drug Candidate for COVID-19 Treatment

1. Amy Q. Wang
2. Natalie R. Hagen
3. Elias C. Padilha
4. Mengbi Yang
5. Pranav Shah
6. Catherine Z. Chen
7. Wenwei Huang
8. Pramod Terse
9. Philip Sanderson
10. Wei Zheng
11. Xin Xu

Reviewed by ScreenIT

Chronic alcohol intake regulates expression of SARS‐CoV2 infection‐relevant genes in an organ‐specific manner

1. Marion M. Friske
2. Francesco Giannone
3. Mona Senger
4. Robin Seitz
5. Anita C. Hansson
6. Rainer Spanagel

Reviewed by ScreenIT

Harringtonine has the effects of double blocking SARS-CoV-2 membrane fusion

1. Shiling Hu
2. Nan Wang
3. Shaohong Chen
4. Qiang Ding
5. Cheng Wang
6. Weina Ma
7. Xinghai Zhang
8. Yan Wu
9. Yanni Lv
10. Zhuoyin Xue
11. Haoyun Bai
12. Shuai Ge
13. Huaizhen He
14. Wen Lu
15. Tao Zhang
16. Yuanyuan Ding
17. Rui Liu
18. Shengli Han
19. Yingzhuan Zhan
20. Guanqun Zhan
21. Zengjun Guo
22. Yongjing Zhang
23. Jiayu Lu
24. Jiapan Gao
25. Qianqian Jia
26. Yuejin Wang
27. Hongliang Wang
28. Shemin Lu
29. Huajun Zhang
30. Langchong He

Reviewed by ScreenIT

NBI-921352, a first-in-class, NaV1.6 selective, sodium channel inhibitor that prevents seizures in Scn8a gain-of-function mice, and wild-type mice and rats

1. JP Johnson
2. Thilo Focken
3. Kuldip Khakh
4. Parisa Karimi Tari
5. Celine Dube
6. Samuel J Goodchild
7. Jean-Christophe Andrez
8. Girish Bankar
9. David Bogucki
10. Kristen Burford
11. Elaine Chang
12. Sultan Chowdhury
13. Richard Dean
14. Gina de Boer
15. Shannon Decker
16. Christoph Dehnhardt
17. Mandy Feng
18. Wei Gong
19. Michael Grimwood
20. Abid Hasan
21. Angela Hussainkhel
22. Qi Jia
23. Stephanie Lee
24. Jenny Li
25. Sophia Lin
26. Andrea Lindgren
27. Verner Lofstrand
28. Janette Mezeyova
29. Rostam Namdari
30. Karen Nelkenbrecher
31. Noah Gregory Shuart
32. Luis Sojo
33. Shaoyi Sun
34. Matthew Taron
35. Matthew Waldbrook
36. Diana Weeratunge
37. Steven Wesolowski
38. Aaron Williams
39. Michael Wilson
40. Zhiwei Xie
41. Rhena Yoo
42. Clint Young
43. Alla Zenova
44. Wei Zhang
45. Alison J Cutts
46. Robin P Sherrington
47. Simon N Pimstone
48. Raymond Winquist
49. Charles J Cohen
50. James R Empfield

• Curated by eLife

  Evaluation Summary:

  This exciting study reports on the characterization of a novel compound that preferentially targets Nav1.6 voltage-gated sodium channels and shows substantial activity against epilepsy associated SCN8A mutations and seizure activity in a variety of animal models. This compound and approach has significant promise to be translated into a therapeutic for individuals with treatment resistant epilepsy.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Favipiravir, umifenovir and camostat mesylate: a comparative study against SARS-CoV-2

1. Mehnmet Altay Unal
2. Omur Besbinar
3. Hasan Nazir
4. Gokce Yagmur Summak
5. Fatma Bayrakdar
6. Lucia Gemma Delogu
7. Tambay Taskin
8. Sibel Aysil Ozkan
9. Kamil Can Akcali
10. Acelya Yilmazer

Reviewed by ScreenIT

Effect of cannabidiol on apoptosis and cellular interferon and interferon-stimulated gene responses to the SARS-CoV-2 genes ORF8, ORF10 and M protein

1. Maria Fernanda Fernandes
2. John Zewen Chan
3. Chia Chun Joey Hung
4. Michelle Victoria Tomczewski
5. Robin Elaine Duncan

Reviewed by ScreenIT

Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels

1. Erika Cecon
2. Daniela Fernandois
3. Nicolas Renault
4. Caio Fernando Ferreira Coelho
5. Jan Wenzel
6. Corentin Bedart
7. Charlotte Izabelle
8. Sarah Gallet
9. Sophie Le Poder
10. Bernard Klonjkowski
11. Markus Schwaninger
12. Vincent Prevot
13. Julie Dam
14. Ralf Jockers

Reviewed by ScreenIT