bims-mevinf 2024-06-02 papers

J Am Nutr Assoc. 2024 May 28. 1-13

Perturbed Lipid Metabolism Transduction Pathways in SARS-CoV-2 Infection and Their Possible Treating Nutraceuticals.

Amrita Shukla, Ankita Singh, Smriti Tripathi.

The coronavirus disease 2019 (COVID-19) epidemic has evolved into an international public health concern. Its causing agent was SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), a lipid bilayer encapsulated virus. Lipids have relevance in the host's viral cycle; additionally; viruses have been speculated to manipulate lipid signaling and production to influence the lipidome of host cells. SARS-CoV-2 engages the host lipid pathways for replication, like fatty acid synthesis activation via upregulation of AKT and SREBP pathway and inhibiting lipid catabolism by AMPK and PPAR deactivation. Consequently, lipoprotein levels are altered in most cases, i.e., raised LDL, TG, VLDL levels and reduced HDL levels like a hyperlipidemic state. Apo lipoproteins, a subsiding structural part of lipoproteins, may also impact viral spike protein binding to host cell receptors. In a few studies conducted on COVID-19 patients, maintaining Apo lipoprotein levels has also shown antiviral activity against SARS-CoV-2 infection. It was speculated that several potent hypolipidemic drugs, such as statins, hydroxychloroquine, and metformin, could be used as add-on treatment in COVID-19 management. Nutraceuticals like Garlic, Fenugreek, and vinegar have the potency to lower the lipid capability acting via these pathways. A link between COVID-19 and post-COVID alteration in lipoprotein levels has not yet been fully understood. In this review, we try to look over the possible modifications in lipid metabolism due to SARS-CoV-2 viral exposure, besides the prospect of focusing on the potential of lipid metabolic processes to interrupt the viral cycle.

Keywords: COVID-19; SARS-CoV-2; hyperlipidemia; nutraceuticals; signaling pathway

DOI: https://doi.org/10.1080/27697061.2024.2359084

J Virol. 2024 May 30. e0045824

IDO1 promotes CSFV replication by mediating tryptophan metabolism to inhibit NF-κB signaling.

Tryptophan metabolism plays a crucial role in facilitating various cellular processes essential for maintaining normal cellular function. Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the conversion of tryptophan (Trp) into kynurenine (Kyn), thereby initiating the degradation of Trp. The resulting Kyn metabolites have been implicated in the modulation of immune responses. Currently, the role of IDO1-mediated tryptophan metabolism in the process of viral infection remains relatively unknown. In this study, we discovered that classical swine fever virus (CSFV) infection of PK-15 cells can induce the expression of IDO1, thereby promoting tryptophan metabolism. IDO1 can negatively regulate the NF-κB signaling by mediating tryptophan metabolism, thereby facilitating CSFV replication. We found that silencing the IDO1 gene enhances the expression of IFN-α, IFN-β, and IL-6 by activating the NF-κB signaling pathway. Furthermore, our observations indicate that both silencing the IDO1 gene and administering exogenous tryptophan can inhibit CSFV replication by counteracting the cellular autophagy induced by Rapamycin. This study reveals a novel mechanism of IDO1-mediated tryptophan metabolism in CSFV infection, providing new insights and a theoretical basis for the treatment and control of CSFV.IMPORTANCEIt is well known that due to the widespread use of vaccines, the prevalence of classical swine fever (CSF) is shifting towards atypical and invisible infections. CSF can disrupt host metabolism, leading to persistent immune suppression in the host and causing significant harm when co-infected with other diseases. Changes in the host's metabolic profiles, such as increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, can also influence virus replication. Mammals utilize various pathways to modulate immune responses through amino acid utilization, including increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, thereby limiting viral replication. Therefore, this study proposes that targeting the modulation of tryptophan metabolism may represent an effective approach to control the progression of CSF.

Keywords: autophagy; classical swine fever virus; indoleamine 2,3-dioxygenase 1 (IDO1); kynurenine; nuclear factor kappa-B (NF-κB); tryptophan

DOI: https://doi.org/10.1128/jvi.00458-24

Sci Rep. 2024 05 30. 14(1): 12406

Metformin is a potential therapeutic for COVID-19/LUAD by regulating glucose metabolism.

Yongwang Hou, Zhicong Yang, Baoli Xiang, Jiangmin Liu, Lina Geng, Dandan Xu, Minghua Zhan, Yuhuan Xu, Bin Zhang.

Lung adenocarcinoma (LUAD) is the most common and aggressive subtype of lung cancer, and coronavirus disease 2019 (COVID-19) has become a serious public health threat worldwide. Patients with LUAD and COVID-19 have a poor prognosis. Therefore, finding medications that can be used to treat COVID-19/LUAD patients is essential. Bioinformatics analysis was used to identify 20 possible metformin target genes for the treatment of COVID-19/LUAD. PTEN and mTOR may serve as hub target genes of metformin. Metformin may be able to cure COVID-19/LUAD comorbidity through energy metabolism, oxidoreductase NADH activity, FoxO signalling pathway, AMPK signalling system, and mTOR signalling pathway, among other pathways, according to the results of bioinformatic research. Metformin has ability to inhibit the proliferation of A549 cells, according to the results of colony formation and proliferation assays. In A549 cells, metformin increased glucose uptake and lactate generation, while decreasing ATP synthesis and the NAD+/NADH ratio. In summary, PTEN and mTOR may be potential targets of metformin for the treatment of COVID-19/LUAD. The mechanism by which metformin inhibits lung adenocarcinoma cell proliferation may be related to glucose metabolism regulated by PI3K/AKT signalling and mTOR signalling pathways. Our study provides a new theoretical basis for the treatment of COVID-19/LUAD.

Keywords: Bioinformatics; COVID-19; Glucose metabolism; LUAD; Metformin

DOI: https://doi.org/10.1038/s41598-024-63081-0

Infection. 2024 May 27.

The roles of the kynurenine pathway in COVID-19 neuropathogenesis.

Mona Dehhaghi, Mostafa Heydari, Hamed Kazemi Shariat Panahi, Sharon R Lewin, Benjamin Heng, Bruce J Brew, Gilles J Guillemin.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders that can be acute, lasting days to weeks or months and possibly longer. The latter is known as long-COVID or more recently post-acute sequelae of COVID (PASC). During acute COVID-19 infection, a strong inflammatory response, known as the cytokine storm, occurs in some patients. The levels of interferon-γ (IFN-γ), interferon-β (IFN-β), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) are particularly increased. These cytokines are known to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing the first step of tryptophan (Trp) catabolism through the kynurenine pathway (KP) leading to the production of several neurotoxic and immunosuppressive metabolites. There is already data showing elevation in KP metabolites both acutely and in PASC, especially regarding cognitive impairment. Thus, it is likely that KP involvement is significant in SARS-CoV-2 pathogenesis especially neurologically.

Keywords: COVID-19; Kynurenine pathway; Long COVID; Neurological manifestations; SARS-CoV-2; Tryptophan

DOI: https://doi.org/10.1007/s15010-024-02293-y