Biochemistry

Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance

1. Ala M. Shaqra
2. Sarah N. Zvornicanin
3. Qiu Yu J. Huang
4. Gordon J. Lockbaum
5. Mark Knapp
6. Laura Tandeske
7. David T. Bakan
8. Julia Flynn
9. Daniel N. A. Bolon
10. Stephanie Moquin
11. Dustin Dovala
12. Nese Kurt Yilmaz
13. Celia A. Schiffer

Reviewed by ScreenIT

Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19

1. Yuto Unoh
2. Shota Uehara
3. Kenji Nakahara
4. Haruaki Nobori
5. Yukiko Yamatsu
6. Shiho Yamamoto
7. Yuki Maruyama
8. Yoshiyuki Taoda
9. Koji Kasamatsu
10. Takahiro Suto
11. Kensuke Kouki
12. Atsufumi Nakahashi
13. Sho Kawashima
14. Takao Sanaki
15. Shinsuke Toba
16. Kentaro Uemura
17. Tohru Mizutare
18. Shigeru Ando
19. Michihito Sasaki
20. Yasuko Orba
21. Hirofumi Sawa
22. Akihiko Sato
23. Takafumi Sato
24. Teruhisa Kato
25. Yuki Tachibana

Reviewed by ScreenIT

Structural diversity of the SARS-CoV-2 Omicron spike

1. Sophie M.-C. Gobeil
2. Rory Henderson
3. Victoria Stalls
4. Katarzyna Janowska
5. Xiao Huang
6. Aaron May
7. Micah Speakman
8. Esther Beaudoin
9. Kartik Manne
10. Dapeng Li
11. Rob Parks
12. Maggie Barr
13. Margaret Deyton
14. Mitchell Martin
15. Katayoun Mansouri
16. Robert J. Edwards
17. Amanda Eaton
18. David C. Montefiori
19. Gregory D. Sempowski
20. Kevin O. Saunders
21. Kevin Wiehe
22. Wilton Williams
23. Bette Korber
24. Barton F. Haynes
25. Priyamvada Acharya

Reviewed by ScreenIT

Converting non-neutralizing SARS-CoV-2 antibodies targeting conserved epitopes into broad-spectrum inhibitors through receptor blockade

1. Payton A.-B. Weidenbacher
2. Eric Waltari
3. Izumi de los Rios Kobara
4. Benjamin N. Bell
5. John E. Pak
6. Peter S. Kim

Reviewed by ScreenIT

Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail

1. Amin Addetia
2. Young-Jun Park
3. Tyler Starr
4. Allison J. Greaney
5. Kaitlin R. Sprouse
6. John E. Bowen
7. Sasha W. Tiles
8. Wesley C. Van Voorhis
9. Jesse D. Bloom
10. Davide Corti
11. Alexandra C. Walls
12. David Veesler

Reviewed by ScreenIT

Molecular architecture of the human tRNA ligase complex

1. Alena Kroupova
2. Fabian Ackle
3. Igor Asanović
4. Stefan Weitzer
5. Franziska M Boneberg
6. Marco Faini
7. Alexander Leitner
8. Alessia Chui
9. Ruedi Aebersold
10. Javier Martinez
11. Martin Jinek

• Curated by eLife

  Evaluation Summary:

  This manuscript describes a tour-de-force approach to determine how the five subunits of the human tRNA ligase complex interact with each other. The authors combine X-ray crystallography of individual protein domains with combinatorial reconstitution analysis and cross-linking mass spectrometry to define and purify a minimal tRNA ligase complex core. Their reductionist and highly analytical approach produces a treasure-trove of data with exceptional quality, the true value of which will become apparent once additional structural information (from e.g. cryo-electron microscopy) becomes available, enabling independent biochemical validation.

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

Reviewed by eLife

Creation of photocyclic vertebrate rhodopsin by single amino acid substitution

1. Kazumi Sakai
2. Yoshinori Shichida
3. Yasushi Imamoto
4. Takahiro Yamashita

• Curated by eLife

  Evaluation Summary:

  This manuscript describes an investigation of the evolution of monostable rhodopsins, typically found in vertebrates. It highlights that single amino acid changes in vertebrate rhodopsins can create a partial bistable retinal pigment that can be photoconverted back to the ground state or it will slowly convert back to the ground state retinal isomer. The rationale for the experiments came from the discovery of a very interesting activation mechanism of the nonvisual pigment Opn5L1. This work has important implications for how our visual pigments have been optimized during evolution, and it contributes important insights into engineering bistable pigments for optogenetic applications.

  (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 name with the authors.)

Reviewed by eLife

Dithiothreitol causes toxicity in C. elegans by modulating the methionine–homocysteine cycle

1. Gokul G
2. Jogender Singh

• Curated by eLife

  Evaluation Summary:

  Thiol agents, such as dithiothreitol (DTT), are toxic to many species, but the mechanisms of toxicity is incompletely understood. In this work, the authors use the animal C. elegans, a small worm, to propose a new mechanisms for how DTT causes organismal growth arrest. Specifically, they suggest that DTT causes reduction in the key molecule S-adenosyl methionine (SAM), which is used as a methyl donor to modify proteins, lipid, and/or other macromolecules. The genetic and supplementation experiments by the authors are compelling, but no direct evidence is provided that SAM levels are indeed lower following exposure of C. elegans to DTT.

  (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

Structural basis for the in vitro efficacy of nirmatrelvir against SARS-CoV-2 variants

1. Samantha E. Greasley
2. Stephen Noell
3. Olga Plotnikova
4. RoseAnn Ferre
5. Wei Liu
6. Ben Bolanos
7. Kimberly Fennell
8. Jennifer Nicki
9. Tim Craig
10. Yuao Zhu
11. Al E. Stewart
12. Claire M. Steppan

Reviewed by ScreenIT

Glypican-1 drives unconventional secretion of fibroblast growth factor 2

1. Carola Sparn
2. Eleni Dimou
3. Annalena Meyer
4. Roberto Saleppico
5. Sabine Wegehingel
6. Matthias Gerstner
7. Severina Klaus
8. Helge Ewers
9. Walter Nickel

• Curated by eLife

  Evaluation Summary:

  FGF2 moves directly from the cytoplasm through the plasma membrane in a reaction driven by its subsequent high affinity binding to cell surface heparan sulfate proteoglycans. This study concludes that Glypican-1 is the principal proteoglycan involved, possibly involving a unique tri-sulfated disaccharide binding site in close proximity to the cell surface. While the role of Glypican-1 appears unique to FGF2 rather than part of a generalized direct secretion mechanism, the observations highlight the complexity and significance of proteoglycan variation. The work is well done and generally convincing, but additional support for the authors' conclusion that a specific glycan structure in GPC1 is a specific ligand for FGF2 is required.

  (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