Modeling vaccination rollouts, SARS-CoV-2 variants and the requirement for non-pharmaceutical interventions in Italy

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(6), P. 993 - 998

Published: April 16, 2021

Despite the progress in medical care, combined population-wide interventions (such as physical distancing, testing and contact tracing) are still crucial to manage SARS-CoV-2 pandemic, aggravated by emergence of new highly transmissible variants. We combine compartmental SIDARTHE model, predicting course COVID-19 infections, with a data-based model that projects cases onto casualties healthcare system costs. Based on Italian case study, we outline several scenarios: mass vaccination campaigns different paces, transmission rates due variants, enforced countermeasures, including alternation opening closure phases. Our results demonstrate non-pharmaceutical (NPIs) have higher impact epidemic evolution than vaccination, which advocates for need keep containment measures place throughout campaign. also show that, if intermittent open-close strategies adopted, deaths costs can be drastically reduced, without any aggravation socioeconomic losses, long one has foresight start closing phase rather an one.

Language: Английский

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Glycyrrhizin Effectively Inhibits SARS-CoV-2 Replication by Inhibiting the Viral Main Protease

Viruses, Journal Year: 2021, Volume and Issue: 13(4), P. 609 - 609

Published: April 2, 2021

The outbreak of SARS-CoV-2 developed into a global pandemic affecting millions people worldwide. Despite one year intensive research, the current treatment options for infected are still limited. Clearly, novel antiviral compounds patients urgently needed. Complementary medicine is used along with standard medical and accessible to vast majority Natural products activity may contribute improve overall condition individuals. In present study, we investigated glycyrrhizin, primary active ingredient licorice root, against SARS-CoV-2. We demonstrated that glycyrrhizin potently inhibits replication in vitro. Furthermore, uncovered underlying mechanism showed blocks viral by inhibiting main protease Mpro essential replication. Our data indicate consumption glycyrrhizin-containing such as root tea black be great benefit people. good candidate further investigation clinical use treat COVID-19 patients.

Language: Английский

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Antimicrobial Resistance Threats in the emerging COVID-19 pandemic: Where do we stand?

Journal of Infection and Public Health, Journal Year: 2021, Volume and Issue: 14(5), P. 555 - 560

Published: March 7, 2021

Antimicrobial resistance (AMR) continues to exert a substantial toll on the global health and world economy is now expected be hidden by COVID-19 for while. The wrong consumption of antibiotics during pandemic will raise disastrous effects AMR management antibiotic stewardship programs. This related concerns extrapolated due an increase in mortality rates patients with bacterial coinfections. Importantly, immune system regions high may fighting two fronts altogether, virus MDR bacteria. Current control policies manage prioritization plans are mandatory this pandemic. review aims discuss rising excess use highlighting role coinfections these patients. Types prescribed development addressed as well.

Language: Английский

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Fungal and bacterial coinfections increase mortality of severely ill COVID-19 patients

Journal of Hospital Infection, Journal Year: 2021, Volume and Issue: 113, P. 145 - 154

Published: April 21, 2021

SARS-CoV-2 predisposes patients to secondary infections; however, a better understanding of the impact coinfections on outcome hospitalized COVID-19 is still necessary.To analyse death risk due in patients.The odds 212 severely ill were evaluated, with detailed focus risks for each pathogen, site infection, comorbidities and length hospitalization.The mortality rate was 50.47%. Fungal and/or bacterial isolation occurred 89 patients, whom 83.14% died. Coinfected stayed longer had an increased dying (odds ratio (OR): 13.45; R2 = 0.31). The by (OR: 11.28) fungal 5.97) coinfections, levels creatinine, leucocytes, urea C-reactive protein. Coinfections if suffered from cardiovascular disease 11.53), diabetes 6.00) or obesity 5.60) comparison these but without pathogen isolation. detected coagulase-negative Staphylococcus 25.39), Candida non-albicans 11.12), S. aureus 10.72), Acinetobacter spp. 6.88), Pseudomonas 4.77), C. albicans 3.97). high-risk sites infection blood, tracheal aspirate, urine. Patients coinfection undergoing invasive mechanical ventilation 3.8 times more likely die than those positive cultures.Severe required hospitalization higher death. early diagnosis essential identify determine right interventions reduce mortality.

Language: Английский

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Fatal COVID-19 pulmonary disease involves ferroptosis

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 20, 2024

Abstract SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining lipidomic analysis autopsies reveal increases ferroptosis markers, including transferrin receptor 1 malondialdehyde accumulation fatal cases. lungs display dysregulation of lipids involved metabolism ferroptosis. We find increased ferritin light chain associated pathology. Iron overload promotes both primary cells cancerous epithelial cells. In addition, markers strongly correlate injury severity a disease model using male Syrian hamsters. These results role for disease; pharmacological inhibition serve as adjuvant therapy to prevent damage during infection.

Language: Английский

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Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

Pathogens, Journal Year: 2021, Volume and Issue: 10(5), P. 565 - 565

Published: May 7, 2021

The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for has been discovered. Recent investigations research studies primarily focus immunopathology disease. A healthy immune system responds immediately after viral entry, causing immediate annihilation recovery. However, an impaired causes extensive systemic damage due to unregulated response characterized hypersecretion chemokines cytokines. elevated levels cytokine or hypercytokinemia leads distress (ARDS) along with multiple organ damage. Moreover, against SARS-CoV-2 linked race, gender, age; hence, this infection's outcome differs among patients. Many therapeutic strategies focusing immunomodulation have tested assuage storm in patients COVID-19. thorough understanding diverse signaling pathways triggered virus essential before contemplating relief measures. This present review explains interrelationships hyperinflammatory severity. Furthermore, we thrown light mechanisms risk factors that influence molecular lead infection Recognition altered dysregulated can be loophole identify potential target markers. Identifying biomarkers pathway aid better clinical management COVID-19 special also given potent inhibitors proinflammatory cytokines, immunomodulatory immunotherapeutic options ameliorate inflammatory responses affected

Language: Английский

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Haste makes waste: A critical review of docking‐based virtual screening in drug repurposing for SARS‐CoV‐2 main protease (M‐pro) inhibition

Medicinal Research Reviews, Journal Year: 2021, Volume and Issue: 42(2), P. 744 - 769

Published: Oct. 26, 2021

This review makes a critical evaluation of 61 peer-reviewed manuscripts that use docking step in virtual screening (VS) protocol to predict SARS-CoV-2 M-pro (M-pro) inhibitors approved or investigational drugs. Various different compounds, even when they similar initial dataset and methodology, most them do not validate their methodology results. In addition, set known 150 extracted from the literature second 81 113 inactive compounds obtained COVID Moonshot project were used evaluate reliability using scores as feasible predictors potency inhibitor. Using two structures five protein-ligand programs, we proved correlation between pIC50 is good. Neither was any found ∆G calculated with an MM-GBSA method. When group experimentally added, neither able distinguish without experimental inhibitory activity. Performances improved covalent noncovalent treated separately, but good enough fully support score cutoff value for selecting new putative predicting relative bioactivity compound by comparison reference compound. The sets presented here could be validating future VS protocols which aim inhibitors.

Language: Английский

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Drug Repurposing for COVID-19: A Review and a Novel Strategy to Identify New Targets and Potential Drug Candidates

Molecules, Journal Year: 2022, Volume and Issue: 27(9), P. 2723 - 2723

Published: April 23, 2022

In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent of disease 2019 (COVID-19) was first identified in province Wuhan, China. Since then, there have been over 400 million confirmed cases and 5.8 deaths by COVID-19 reported worldwide. The urgent need for therapies against SARS-CoV-2 led researchers to use drug repurposing approaches. This strategy allows reduction risks, time, costs associated with development. many cases, a repurposed can enter directly preclinical testing clinical trials, thus accelerating whole discovery process. this work, we will give general overview main developments treatment, focusing on contribution paradigm find effective drugs disease. Finally, present our findings using new that 11 compounds may be potentially COVID-19. To knowledge, seven these never tested are potential candidates vitro vivo studies evaluate their effectiveness treatment.

Language: Английский

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Discovery and Crystallographic Studies of Trisubstituted Piperazine Derivatives as Non-Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity and Low Toxicity

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(19), P. 13343 - 13364

Published: Sept. 15, 2022

The continuous spread of SARS-CoV-2 calls for more direct-acting antiviral agents to combat the highly infectious variants. main protease (Mpro) is an promising target anti-SARS-CoV-2 drug design. Here, we report discovery potent non-covalent non-peptide Mpro inhibitors featuring a 1,2,4-trisubstituted piperazine scaffold. We systematically modified hit MCULE-5948770040 by structure-based rational design combined with multi-site binding and privileged structure assembly strategies. optimized compound GC-14 inhibits high potency (IC50 = 0.40 μM) displays excellent activity (EC50 1.1 μM), being than Remdesivir. Notably, exhibits low cytotoxicity (CC50 > 100 selectivity 50 μM cathepsins B, F, K, L, caspase 3). X-ray co-crystal structures prove that occupy multiple subpockets critical interactions. These studies may provide basis developing efficient safer therapy COVID-19.

Language: Английский

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Mitochondrial health quality control: measurements and interpretation in the framework of predictive, preventive, and personalized medicine

The EPMA Journal, Journal Year: 2022, Volume and Issue: 13(2), P. 177 - 193

Published: May 12, 2022

Abstract Mitochondria are the “gatekeeper” in a wide range of cellular functions, signaling events, cell homeostasis, proliferation, and apoptosis. Consequently, mitochondrial injury is linked to systemic effects compromising multi-organ functionality. Although stress common for many pathomechanisms, individual outcomes differ significantly comprising spectrum associated pathologies their severity grade. highly ambitious task paradigm shift from reactive predictive, preventive, personalized medicine (PPPM/3PM) distinguish between disease predisposition progression under circumstances, resulting compromised health followed by mitigating measures tailored individualized patient profile. For successful implementation PPPM concepts, robust parameters essential quantify sustainability. The current article analyses added value Mitochondrial Health Index (MHI) Bioenergetic (BHI) as potential systems relevant development its Based on pathomechanisms related context primary, secondary, tertiary care, broad conditions can benefit quantification using MHI/BHI prototype be further improved. Following that: planned pregnancies (improved mother offspring health), suboptimal with reversible damage, life-style patterns metabolic syndrome(s) predisposition, multi-factorial conditions, genotoxic environment, ischemic stroke unclear aetiology, phenotypic aggressive cancer subtypes, premature aging neuro/degeneration, acute infectious diseases such COVID-19 pandemics, among others.

Language: Английский

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