COVID‐19 metabolism: Mechanisms and therapeutic targets

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) dysregulates antiviral signaling, immune response, and cell metabolism in human body. Viral genome and proteins hijack host metabolic network to support viral biogenesis and propagation. However, the regulatory mechanism of SARS‐CoV‐2‐induced metabolic dysfunction has not been elucidated until recently. Multiomic studies of coronavirus disease 2019 (COVID‐19) revealed an intensive interaction between host metabolic regulators and viral proteins. SARS‐CoV‐2 deregulated cellular metabolism in blood, intestine, liver, pancreas, fat, and immune cells. Host metabolism supported almost every stage of viral lifecycle. Strikingly, viral proteins were found to interact with metabolic enzymes in different cellular compartments. Biochemical and genetic assays also identified key regulatory nodes and metabolic dependencies of viral replication. Of note, cholesterol metabolism, lipid metabolism, and glucose metabolism are broadly involved in viral lifecycle. Here, we summarized the current understanding of the hallmarks of COVID‐19 metabolism. SARS‐CoV‐2 infection remodels host cell metabolism, which in turn modulates viral biogenesis and replication. Remodeling of host metabolism creates metabolic vulnerability of SARS‐CoV‐2 replication, which could be explored to uncover new therapeutic targets. The efficacy of metabolic inhibitors against COVID‐19 is under investigation in several clinical trials. Ultimately, the knowledge of SARS‐CoV‐2‐induced metabolic reprogramming would accelerate drug repurposing or screening to combat the COVID‐19 pandemic.

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID

“…Consistent with protein-host interactions whose consequences lie in mitochondrial dysfunctions, the SARS-CoV-2 nsp12 protein has been suggested to inhibit branched-chain keto acid dehydrogenase kinase (BCKDK), a branched-chain amino acid kinase regulatory enzyme [26,43]. Interestingly, the accumulation of branchedchain amino acids, which in turn can inhibit pyruvate dehydrogenase, mitochondrial respiration chain and α-ketoglutarate dehydrogenase, can cause apoptosis in glial cells and neurons [44].…”

“…In addition to the interactions aforementioned, SARS-CoV-2 can also alter both mitochondrial protein synthesis and transport. On the one hand, nsp8 protein, which has been described to interact with neuroguidine (NGDN), asparaginyl-tRNA synthetase 2 (NARS2) and mitochondrial ribosomal protein S5, 25 and 27 (MRPS5, 25 and 27), could alter the modulation of mitochondrial protein synthesis [26,35,36], as well as interact with the ETC complex [37]. On the other hand, the nsp10 protein could modulate protein transport from the inner mitochondrial membrane to the mitochondrial matrix through its interaction with the host protein GRPEL1 (GrpE protein homolog 1) [26], whose functional significance remains unclear, although its loss has been described as leading to mitochondrial oxidation of fatty acids and arrest of oxidative phosphorylation in musculoskeletal cells, along with rapid muscle atrophy [38] the nucleus by connecting to the nuclear transcriptional activity of mitochondrial proteins [40].…”

Mouthwashes and the Effect on the Viral Load of SARS-CoV-2 in Saliva: A Literature Review

“…Dental physicians and surgeons are continually at risk of possible COVID-19 infection due to the procedures they perform by being in close proximity to the patients with and without symptoms [4], [11]. Clinically, severe COVID-19 infection has been described by the appearance of certain events such as a strong inflammatory response from the immune system, lymphopenia, thrombocytopenia, and coagulopathies [3]. Several collection sites have been described in the literature to study the viral load in COVID-19, including nasopharynx, sputum, saliva, plasma, urine, and feces.…”

“…After more than 2 years of its appearance, the most effective measures to prevent the transmission of severe acute respiratory syndrome by coronavirus 2 (SARS-CoV-2) continue to be public health interventions, in this case immunization and social distancing [1], [2]. In the meantime, progress in the clinical treatment of COVID-19 patients has not yet achieved the goals set by the researchers, due to most drugs that had antiviral efficacy in vitro were found to be ineffective in the clinical treatment of COVID-19 [3].…”

SARS-CoV-2 Invasion and Pathological Links to Prion Disease

“…The viral infection of human host cells often involves the direct recognition, binding, and interaction of the virus particle with a naturally occurring host cell surface receptor that protrudes from cholesterol-enriched lipid raft domains in the viral lipoprotein envelope (see Section 2 . SARS-CoV-2—Structure, Function and Neuroinvasion ) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. In the case of COVID-19, the SARS-CoV-2 ‘S1’ spike protein interacts specifically with the angiotensin-converting enzyme 2 receptor (ACE2R; EC 3.4.17.23; ; last accessed on 30 August 2022), which is located on multiple host cell surfaces.…”