Hirabara Sandro Massao, Gorjao Renata, Levada-Pires Adriana Cristina, Masi Laureane Nunes, Hatanaka Elaine, Cury-Boaventura Maria Fernanda, da Silva Eliane Borges, Santos-Oliveira Laiane Cristina Dos, Sousa Diniz Vinicius Leonardo, Serdan Tamires Afonso Duarte, de Oliveira Vivian Araujo Barbosa, de Souza Diego Ribeiro, Gritte Raquel Bragante, Souza-Siqueira Talita, Zambonatto Raquel Freitas, Pithon-Curi Tania Cristina, Bazotte Roberto Barbosa, Newsholme Philip, Curi Rui
Interdisciplinary Program of Health Sciences, Cruzeiro do Sul University, GalvãoBueno, 868, Liberdade, 01506-000, SãoPaulo, São Paulo, Brazil.
Post-Graduate Program in Pharmaceutical Sciences, State University of Maringá, Paraná State, Brazil.
Clin Sci (Lond). 2021 Jan 29;135(2):305-325. doi: 10.1042/CS20201042.
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.
病毒至少包含由蛋白质衣壳包裹的核酸基因组。基因组和衣壳合称为核衣壳，其具有包膜，该包膜含有源自宿主细胞膜的脂质双层（主要是磷脂）。病毒包膜具有通常为糖蛋白的跨膜蛋白。包膜中的蛋白质与宿主细胞受体结合，促进膜融合和病毒进入细胞。病毒感染的宿主细胞在谷氨酰胺利用和代谢方面表现出显著增加。谷氨酰胺代谢产生ATP以及用于合成大分子以组装子代病毒的前体。一些源自谷氨酰胺的化合物用于嘌呤和嘧啶的合成。后一类化合物是核苷酸合成的前体。谷氨酰胺转运和代谢的抑制剂是潜在的抗病毒药物候选物。谷氨酰胺也是白细胞（淋巴细胞、巨噬细胞和中性粒细胞）功能所必需的营养素，包括病毒感染患者体内的白细胞。病毒感染患者免疫细胞功能对谷氨酰胺需求的增加与宿主细胞对谷氨酰胺的高利用率同时出现。那么，开发针对谷氨酰胺代谢的抗病毒药物必须专门针对病毒感染的宿主细胞，以避免对免疫功能产生负面影响。因此，本综述的目的是描述细胞谷氨酰胺代谢的概况，以寻找抑制谷氨酰胺转运或谷氨酰胺代谢的潜在候选物。
