Host cell glutamine metabolism as a potential antiviral target.

A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. The proteins in the envelope bind to host cell receptors, promoting membrane fusion and viral entry into the cell. Virus-infected host cells exhibit marked increases in glutamine utilization and metabolism. Glutamine metabolism generates ATP and precursors for the synthesis of macromolecules to assemble progeny viruses. Some compounds derived from glutamine are used in the synthesis of purines and pyrimidines. These latter compounds are precursors for the synthesis of nucleotides. Inhibitors of glutamine transport and metabolism are potential candidate antiviral drugs. Glutamine is also an essential nutrient for the functions of leukocytes (lymphocyte, macrophage, and neutrophil), including those in virus-infected patients. The increased glutamine requirement for immune cell functions occurs concomitantly with the high glutamine utilization by host cells in virus-infected patients. The development of antiviral drugs that target glutamine metabolism must then be specifically directed at virus-infected host cells to avoid negative effects on immune functions. Therefore, the aim of this review was to describe the landscape of cellular glutamine metabolism to search for potential candidates to inhibit glutamine transport or glutamine metabolism. © 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Citation

Sandro Massao Hirabara, Renata Gorjao, Adriana Cristina Levada-Pires, Laureane Nunes Masi, Elaine Hatanaka, Maria Fernanda Cury-Boaventura, Eliane Borges da Silva, Laiane Cristina Dos Santos-Oliveira, Vinicius Leonardo Sousa Diniz, Tamires Afonso Duarte Serdan, Vivian Araujo Barbosa de Oliveira, Diego Ribeiro de Souza, Raquel Bragante Gritte, Talita Souza-Siqueira, Raquel Freitas Zambonatto, Tania Cristina Pithon-Curi, Roberto Barbosa Bazotte, Philip Newsholme, Rui Curi. Host cell glutamine metabolism as a potential antiviral target. Clinical science (London, England : 1979). 2021 Jan 29;135(2):305-325

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PMID: 33480424

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