The Antiviral Compound PSP Inhibits HIV-1 Entry via PKR-Dependent Activation in Monocytic Cells

Alvarez-Rivera, Eduardo; Rodríguez-Valentín, Madeline; Boukli, Nawal M.

doi:10.3390/v15030804

Cited by 4 publications

(3 citation statements)

References 92 publications

(124 reference statements)

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“…The actin cytoskeleton plays important roles in most cellular processes, including mechanical support, cell migration, differentiation, and signaling pathways. F‐actin contributes to morphology, trafficking, migration, and adhesion through continuous polymerization and depolymerization (Alvarez‐Rivera et al., 2023 ). Cucurbitacins generally affect the organization of the actin cytoskeleton, causing changes in the cells' normal actin dynamics and actin aggregate formation.…”

Section: Discussionmentioning

confidence: 99%

Depolymerization of actin filaments by Cucurbitacin I through binding G‐actin

Haciosmanoglu Aldogan,

Önsü,

Saylan

et al. 2023

Food Science & Nutrition

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Cucurbitacins have high economic value as they are a major source of food and have pharmacological properties. Cucurbitacin I (CuI) is a plant‐derived natural tetracyclic triterpenoid compound that shows an anticancer effect via inhibiting the JAK2‐STAT3 signaling pathway. The actin cytoskeleton is the most abundant protein in cells and regulates critical events through reorganization in cells. In this study, it is aimed at determining the direct effect of CuI on actin dynamics. The fluorescence profile of G‐actin in the presence of CuI (1–200 nM) shifted to a higher temperature, suggesting that G‐actin binds CuI and that G‐actin–CuI is more thermally stable than the ligand‐free form. CuI dose‐dependently inhibited the polymerization of F‐actin in vitro and disrupted actin filaments in endothelial cells. Docking and MD simulations suggested that CuI binds to the binding site formed by residues I136, I175, D154, and A138 that are at the interface of monomers in F‐actin. The migration ability of cells treated with CuI for 24 h was significantly lower than the control group (p < .001). This study reveals the molecular mechanisms of CuI in the regulation of actin dynamics by binding G‐actin. More importantly, this study indicates a novel role of CuI as an actin‐targeting drug by binding directly to G‐actin and may contribute to the mode of action of CuI on anticancer activities.

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Section: Discussionmentioning

confidence: 99%

Depolymerization of actin filaments by Cucurbitacin I through binding G‐actin

Haciosmanoglu Aldogan,

Önsü,

Saylan

et al. 2023

Food Science & Nutrition

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“…Interestingly, PSP demonstrates the ability to extend its anti-cancer effects towards the immune system by inhibiting HIV-1 replication in THP1 and peripheral blood mononuclear cells through the upregulation of antiviral chemokines [ 187 ]. It has also been observed to target the entryway through overlapping signaling between UPR marker IRE1α and PKR in monocytes [ 188 ]. This review provides deeper insight into common overlapping pathways that are shared among predominant oncogenic disturbances as well as triggered during HIV-1 infections ( Figure 3 ).…”

Section: Signaling Pathways In Cancer: Mutual Crosstalk Between Er St...mentioning

confidence: 99%

Oncogenic Proteomics Approaches for Translational Research and HIV-Associated Malignancy Mechanisms

Alvarez-Rivera,

Ortiz-Hernández,

Lugo

et al. 2023

Proteomes

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Recent advances in the field of proteomics have allowed extensive insights into the molecular regulations of the cell proteome. Specifically, this allows researchers to dissect a multitude of signaling arrays while targeting for the discovery of novel protein signatures. These approaches based on data mining are becoming increasingly powerful for identifying both potential disease mechanisms as well as indicators for disease progression and overall survival predictive and prognostic molecular markers for cancer. Furthermore, mass spectrometry (MS) integrations satisfy the ongoing demand for in-depth biomarker validation. For the purpose of this review, we will highlight the current developments based on MS sensitivity, to place quantitative proteomics into clinical settings and provide a perspective to integrate proteomics data for future applications in cancer precision medicine. We will also discuss malignancies associated with oncogenic viruses such as Acquire Immunodeficiency Syndrome (AIDS) and suggest novel mechanisms behind this phenomenon. Human Immunodeficiency Virus type-1 (HIV-1) proteins are known to be oncogenic per se, to induce oxidative and endoplasmic reticulum stresses, and to be released from the infected or expressing cells. HIV-1 proteins can act alone or in collaboration with other known oncoproteins, which cause the bulk of malignancies in people living with HIV-1 on ART.

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“…Accordingly, new molecular insights into how UPR, IFN-IP, and cytoskeletal events interact are provided by the current study. Interestingly, the information presented in the article suggested that PSP may be utilized as a natural alternative to stop HIV-1 entrance [ 10 ]. In a communication article authored by Zhu and collaborators, the mechanism of the molecular recognition of the HIV-1 gp120 V3 loop by the coreceptor CXC chemokine receptor 4 (CXCR4) was investigated using a construct containing the V3 loop (full-length).…”

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confidence: 99%