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A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin.
De Jesús-González, LA, Del Ángel, RM, Palacios-Rápalo, SN, Cordero-Rivera, CD, Rodríguez-Carlos, A, Trujillo-Paez, JV, Farfan-Morales, CN, Osuna-Ramos, JF, Reyes-Ruiz, JM, Rivas-Santiago, B, et al
Microorganisms. 2024;(2)
Abstract
Metformin (MET) and atorvastatin (ATO) are promising treatments for COVID-19. This review explores the potential of MET and ATO, commonly prescribed for diabetes and dyslipidemia, respectively, as versatile medicines against SARS-CoV-2. Due to their immunomodulatory and antiviral capabilities, as well as their cost-effectiveness and ubiquitous availability, they are highly suitable options for treating the virus. MET's effect extends beyond managing blood sugar, impacting pathways that can potentially decrease the severity and fatality rates linked with COVID-19. It can partially block mitochondrial complex I and stimulate AMPK, which indicates that it can be used more widely in managing viral infections. ATO, however, impacts cholesterol metabolism, a crucial element of the viral replicative cycle, and demonstrates anti-inflammatory characteristics that could modulate intense immune reactions in individuals with COVID-19. Retrospective investigations and clinical trials show decreased hospitalizations, severity, and mortality rates in patients receiving these medications. Nevertheless, the journey from observing something to applying it in a therapeutic setting is intricate, and the inherent diversity of the data necessitates carefully executed, forward-looking clinical trials. This review highlights the requirement for efficacious, easily obtainable, and secure COVID-19 therapeutics and identifies MET and ATO as promising treatments in this worldwide health emergency.
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Collateral Damage in the Placenta during Viral Infection in Pregnancy: A Possible Mechanism for Vertical Transmission and an Adverse Pregnancy Outcome.
Cruz-Holguín, VJ, González-García, LD, Velázquez-Cervantes, MA, Arévalo-Romero, H, De Jesús-González, LA, Helguera-Repetto, AC, León-Reyes, G, Salazar, MI, Cedillo-Barrón, L, León-Juárez, M
Diseases (Basel, Switzerland). 2024;(3)
Abstract
In mammals, the placenta is a connection between a mother and a new developing organism. This tissue has a protective function against some microorganisms, transports nutrients, and exchanges gases and excretory substances between the mother and the fetus. Placental tissue is mainly composed of chorionic villi functional units called trophoblasts (cytotrophoblasts, the syncytiotrophoblast, and extravillous trophoblasts). However, some viruses have developed mechanisms that help them invade the placenta, causing various conditions such as necrosis, poor perfusion, and membrane rupture which, in turn, can impact the development of the fetus and put the mother's health at risk. In this study, we collected the most relevant information about viral infection during pregnancy which can affect both the mother and the fetus, leading to an increase in the probability of vertical transmission. Knowing these mechanisms could be relevant for new research in the maternal-fetal context and may provide options for new therapeutic targets and biomarkers in fetal prognosis.
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Dynamics of the Microbiota and Its Relationship with Post-COVID-19 Syndrome.
Moreno-Corona, NC, López-Ortega, O, Pérez-Martínez, CA, Martínez-Castillo, M, De Jesús-González, LA, León-Reyes, G, León-Juárez, M
International journal of molecular sciences. 2023;(19)
Abstract
Coronavirus disease (COVID-19) is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be asymptomatic or present with multiple organ dysfunction. Many infected individuals have chronic alterations associated with neuropsychiatric, endocrine, gastrointestinal, and musculoskeletal symptoms, even several months after disease onset, developing long-COVID or post-acute COVID-19 syndrome (PACS). Microbiota dysbiosis contributes to the onset and progression of many viral diseases, including COVID-19 and post-COVID-19 manifestations, which could serve as potential diagnostic and prognostic biomarkers. This review aimed to discuss the most recent findings on gut microbiota dysbiosis and its relationship with the sequelae of PACS. Elucidating these mechanisms could help develop personalized and non-invasive clinical strategies to identify individuals at a higher risk of experiencing severe disease progression or complications associated with PACS. Moreover, the review highlights the importance of targeting the gut microbiota composition to avoid dysbiosis and to develop possible prophylactic and therapeutic measures against COVID-19 and PACS in future studies.
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Anti-flavivirus Properties of Lipid-Lowering Drugs.
Farfan-Morales, CN, Cordero-Rivera, CD, Reyes-Ruiz, JM, Hurtado-Monzón, AM, Osuna-Ramos, JF, González-González, AM, De Jesús-González, LA, Palacios-Rápalo, SN, Del Ángel, RM
Frontiers in physiology. 2021;:749770
Abstract
Although Flaviviruses such as dengue (DENV) and zika (ZIKV) virus are important human pathogens, an effective vaccine or antiviral treatment against them is not available. Hence, the search for new strategies to control flavivirus infections is essential. Several studies have shown that the host lipid metabolism could be an antiviral target because cholesterol and other lipids are required during the replicative cycle of different Flaviviridae family members. FDA-approved drugs with hypolipidemic effects could be an alternative for treating flavivirus infections. However, a better understanding of the regulation between host lipid metabolism and signaling pathways triggered during these infections is required. The metabolic pathways related to lipid metabolism modified during DENV and ZIKV infection are analyzed in this review. Additionally, the role of lipid-lowering drugs as safe host-targeted antivirals is discussed.
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5.
Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry.
Palacios-Rápalo, SN, De Jesús-González, LA, Cordero-Rivera, CD, Farfan-Morales, CN, Osuna-Ramos, JF, Martínez-Mier, G, Quistián-Galván, J, Muñoz-Pérez, A, Bernal-Dolores, V, Del Ángel, RM, et al
Frontiers in immunology. 2021;:796855
Abstract
Since its appearance, the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), the causal agent of Coronavirus Disease 2019 (COVID-19), represents a global problem for human health that involves the host lipid homeostasis. Regarding, lipid rafts are functional membrane microdomains with highly and tightly packed lipid molecules. These regions enriched in sphingolipids and cholesterol recruit and concentrate several receptors and molecules involved in pathogen recognition and cellular signaling. Cholesterol-rich lipid rafts have multiple functions for viral replication; however, their role in SARS-CoV-2 infection remains unclear. In this review, we discussed the novel evidence on the cholesterol-rich lipid rafts as a platform for SARS-CoV-2 entry, where receptors such as the angiotensin-converting enzyme-2 (ACE-2), heparan sulfate proteoglycans (HSPGs), human Toll-like receptors (TLRs), transmembrane serine proteases (TMPRSS), CD-147 and HDL-scavenger receptor B type 1 (SR-B1) are recruited for their interaction with the viral spike protein. FDA-approved drugs such as statins, metformin, hydroxychloroquine, and cyclodextrins (methyl-β-cyclodextrin) can disrupt cholesterol-rich lipid rafts to regulate key molecules in the immune signaling pathways triggered by SARS-CoV-2 infection. Taken together, better knowledge on cholesterol-rich lipid rafts in the SARS-CoV-2-host interactions will provide valuable insights into pathogenesis and the identification of novel therapeutic targets.