Pharmacology and Toxicology

µ-Theraphotoxin Pn3a inhibition of CaV3.3 channels reveals a novel isoform-selective drug binding site

1. Jeffrey R McArthur
2. Jierong Wen
3. Andrew Hung
4. Rocio K Finol-Urdaneta
5. David J Adams

• Curated by eLife

  Evaluation Summary:

  Low voltage-activated T-type calcium channels (CaV3.1-3.3) are important for several physiological processes. It is challenging to distinguish their specific physiological / pathophysiological roles as they share similar biophysical properties, expression profiles and there is a lack of subtype selective pharmacology. This study reports a spider toxin, Pn3a, which exhibits 100-fold selectivity for inhibiting CaV3.3 over CaV3.1 and CaV3.2 isoforms, and which therefore makes for an excellent reagent for the physiological study of CaV3.3.

  (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

Characterization of the endogenous DAF-12 ligand and its use as an anthelmintic agent in Strongyloides stercoralis

1. Zhu Wang
2. Mi Cheong Cheong
3. Jet Tsien
4. Heping Deng
5. Tian Qin
6. Jonathan DC Stoltzfus
7. Tegegn G Jaleta
8. Xinshe Li
9. James B Lok
10. Steven A Kliewer
11. David J Mangelsdorf

• Curated by eLife

  Evaluation Summary:

  This work reveals the pathway by which an important human parasite synthesizes a nuclear hormone receptor ligand critical for progression through its life cycle and demonstrates the potential therapeutic implications of perturbing this pathway. The experiments are insightfully and expertly conceived, designed and executed, and the data support the conclusions. This manuscript will be of general interest to parasitologists, nematode biologists, and those studying transcriptional regulatory networks governed by ligand-gated nuclear receptors.

  (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 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

Covalent inhibition of endoplasmic reticulum chaperone GRP78 disconnects the transduction of ER stress signals to inflammation and lipid accumulation in diet-induced obese mice

1. Dan Luo
2. Ni Fan
3. Xiuying Zhang
4. Fung Yin Ngo
5. Jia Zhao
6. Wei Zhao
7. Ming Huang
8. Ding Li
9. Yu Wang
10. Jianhui Rong

• Curated by eLife

  Evaluation Summary:

  This paper is of interest to a broad audience of cell biologists, pharmacologists and researchers who work in metabolic diseases. The work provides substantial new insights into the mechanism of action for a plant derived pentacyclic triterpene called celastrol elastrol, in effectively reducing the high fat diet induced tissue hypertrophy in mouse liver and adipose. A series of compelling experiments depict the site of covalent inhibition of the ER stress sensor GRP78 as essential for the beneficial effects in-vivo, supporting the main conclusions.

  (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

Predicting drug polypharmacology from cell morphology readouts using variational autoencoder latent space arithmetic

1. Yuen Ler Chow
2. Shantanu Singh
3. Anne E. Carpenter
4. Gregory P. Way

Reviewed by Review Commons

Bisphosphonate drugs have actions in the lung and inhibit the mevalonate pathway in alveolar macrophages

1. Marcia A Munoz
2. Emma K Fletcher
3. Oliver P Skinner
4. Julie Jurczyluk
5. Esther Kristianto
6. Mark P Hodson
7. Shuting Sun
8. Frank H Ebetino
9. David R Croucher
10. Philip M Hansbro
11. Jacqueline R Center
12. Michael J Rogers

• Curated by eLife

  Evaluation Summary:

  The manuscript by Munoz et al describes the effect of the bisphosphonate zoledronic acid on tissue-resident macrophages. For this, the investigators used both a fluorescent bisphosphonate derivative and an unmodified zoledronic acid, in combination with macrophage populations isolated from different tissues. Based on the pattern of cytokines released by macrophages in the presence of zoledronic acid, the authors conclude that administration of bisphosphonates could, in addition to preventing bone loss, boost immune responses and lessen the consequences of respiratory infections.

  (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, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

"Repurposed Nystatin to Inhibit SARS-Cov-2 and Mutants in the GI Tract"

1. Eszter Virág

Reviewed by ScreenIT

Discovery of Triple Inhibitors of Both SARS-CoV-2 Proteases and Human Cathepsin L

1. Ittipat Meewan
2. Jacob Kattoula
3. Julius Y. Kattoula
4. Danielle Skinner
5. Pavla Fajtová
6. Miriam A. Giardini
7. Brendon Woodworth
8. James H. McKerrow
9. Jair Lage de Siqueira-Neto
10. Anthony J. O’Donoghue
11. Ruben Abagyan

Reviewed by ScreenIT

Oral Lisinopril Raises Tissue Levels of ACE2, the SARS-CoV-2 Receptor, in Healthy Male and Female Mice

1. Steven D. Brooks
2. Rachel L. Smith
3. Aline S. Moreira
4. Hans C. Ackerman

Reviewed by ScreenIT

AUG-3387, a Human-Derived Monoclonal Antibody Neutralizes SARS-CoV-2 Variants and Reduces Viral Load from Therapeutic Treatment of Hamsters In Vivo

1. Christopher J. Emig
2. Marco A. Mena
3. Steven J. Henry
4. Adela Vitug
5. Christian John Ventura
6. Douglas Fox
7. Xammy Huu Nguyenla
8. Haiyue Xu
9. Chaeho Moon
10. Sawittree Sahakijjpijarn
11. Philip J. Kuehl
12. David Revelli
13. Zengrong Cui
14. Robert O. Williams
15. Dale J. Christensen

Reviewed by ScreenIT

A high throughput screening assay for inhibitors of SARS-CoV-2 pseudotyped particle entry

1. Miao Xu
2. Manisha Pradhan
3. Kirill Gorshkov
4. Jennifer D. Petersen
5. Min Shen
6. Hui Guo
7. Wei Zhu
8. Carleen Klumpp-Thomas
9. Sam Michael
10. Misha Itkin
11. Zina Itkin
12. Marco R. Straus
13. Joshua Zimmerberg
14. Wei Zheng
15. Gary R. Whittaker
16. Catherine Z. Chen

Reviewed by ScreenIT