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Reviews of "Inhibiting Glutamine Metabolism Blocks Coronavirus Replication in Mammalian Cells"

Reviewers: J P S Peron (University of Massachusetts) | 📗📗📗📗◻️ • E Berber (Cleveland Clinic) | 📒📒📒◻️◻️• A Chuard (Boston College) | 📗📗📗📗◻️

Published onOct 28, 2023
Reviews of "Inhibiting Glutamine Metabolism Blocks Coronavirus Replication in Mammalian Cells"
key-enterThis Pub is a Review of
Inhibiting Glutamine Metabolism Blocks Coronavirus Replication in Mammalian Cells
Inhibiting Glutamine Metabolism Blocks Coronavirus Replication in Mammalian Cells
Description

Developing therapeutic strategies against COVID-19 has gained widespread interest given the likelihood that new viral variants will continue to emerge. Here we describe one potential therapeutic strategy which involves targeting members of the glutaminase family of mitochondrial metabolic enzymes (GLS and GLS2), which catalyze the first step in glutamine metabolism, the hydrolysis of glutamine to glutamate. We show three examples where GLS expression increases during coronavirus infection of host cells, and another in which GLS2 is upregulated. The viruses hijack the metabolic machinery responsible for glutamine metabolism to generate the building blocks for biosynthetic processes and satisfy the bioenergetic requirements demanded by the "glutamine addiction" of virus-infected host cells. We demonstrate how genetic silencing of glutaminase enzymes reduces coronavirus infection and that newer members of two classes of small molecule allosteric inhibitors targeting these enzymes, designated as SU1, a pan-GLS/GLS2 inhibitor, and UP4, which is specific for GLS, block viral replication in mammalian epithelial cells. Overall, these findings highlight the importance of glutamine metabolism for coronavirus replication in human cells and show that glutaminase inhibitors can block coronavirus infection and thereby may represent a novel class of anti-viral drug candidates.

To read the original manuscript, click the link above.

Summary of Reviews: This preprint demonstrates that coronaviruses hijack host cell glutamine metabolism for replication by upregulating glutaminase enzymes. The reviewers found the rationale and experiments valid and recognized the novelty of showing glutaminase inhibitors like SU1 and UP4 can block coronavirus infection by preventing replication. However, one reviewer suggested experiments to examine effects on viral particle release and cell viability after drug/gene silencing. Also, SARS-CoV-2's glutamine dependence has been shown, so discussion of prior work is recommended. Overall, the study highlights the essential role of glutamine metabolism for coronavirus infection and potential of targeting it as an antiviral strategy.

Reviewer 1 (Jean Pierre S…) | 📗📗📗📗◻️

Reviewer 2 (Engin B…) | 📒📒📒 ◻️◻️

Reviewer 1 (Aurelien C…) | 📗📗📗📗◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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khaber khaber:

نجار الكويت هو فنان ماهر في صناعة الأثاث والأعمال الخشبية. يمتاز نجارو الكويت بمهاراتهم الفريدة في تصميم وصنع الأثاث الجميل والعمل الخشبي المتقن. يستخدمون مواد عالية الجودة ويتقنون فنون التقشير والنحت على الخشب لإنتاج قطع فنية فريدة من نوعها. تعكس أعمالهم التقليدية والحديثة تراث الكويت الثقافي والفني، وتجمع بين الجمالية والوظيفة. إن نجارو الكويت يلعبون دورًا مهمًا في الحفاظ على التراث الحرفي وتطوير صناعة الأثاث في البلاد، ويشكلون جزءًا مهمًا من الهوية الثقافية للكويت.

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