Long COVID science, research and policy

Nature Medicine, Год журнала: 2024, Номер 30(8), С. 2148 - 2164

Опубликована: Авг. 1, 2024

Long COVID represents the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection; it is a complex, multisystem disorder that can affect nearly every organ system be severely disabling. The cumulative global incidence long around 400 million individuals, which estimated to have an annual economic impact approximately $1 trillion-equivalent about 1% economy. Several mechanistic pathways are implicated in COVID, including viral persistence, immune dysregulation, mitochondrial dysfunction, complement endothelial inflammation microbiome dysbiosis. devastating impacts on individual lives and, due its complexity prevalence, also has major ramifications for systems economies, even threatening progress toward achieving Sustainable Development Goals. Addressing challenge requires ambitious coordinated-but so far absent-global research policy response strategy. In this interdisciplinary review, we provide synthesis state scientific evidence assess human health, systems, economy metrics, forward-looking roadmap.

Язык: Английский

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SARS-CoV-2 Drug Resistance and Therapeutic Approaches

Heliyon, Год журнала: 2025, Номер 11(2), С. e41980 - e41980

Опубликована: Янв. 1, 2025

Язык: Английский

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Treating Acute Covid-19 — Final Chapters Still Unwritten

New England Journal of Medicine, Год журнала: 2024, Номер 390(13), С. 1234 - 1236

Опубликована: Апрель 3, 2024

treatment with lixisenatide was statistically significant but small.The importance of this finding is not the magnitude change what it portends.Indeed, primary concern most patients Parkinson's disease their present condition -it fear progression disease.If a three-point improvement in score on MDS-UPDRS that can be achieved lixisenatide, then value drug may limited (especially view adverse effects).On other hand, if benefit cumulative, adding another three points each year over period 5 to 10 years or more, could truly transformative treatment.The next step clearly trials longer duration see whether GLP-1 receptor agonists live up Dr. prediction.

Язык: Английский

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An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations

Science Translational Medicine, Год журнала: 2024, Номер 16(738)

Опубликована: Март 13, 2024

Inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M pro ) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing severity COVID-19, but presence resistance-conferring mutations sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function against these mutants are thus urgently needed. We hypothesized covalent hepatitis C virus inhibitor boceprevir (BPV) could serve basis for orally bioavailable inhibit SARS-CoV-2 M more efficiently than existing drugs. Performing structure-guided modifications BPV, we developed a picomolar-affinity inhibitor, ML2006a4, with antiviral activity, pharmacokinetics, therapeutic efficacy similar or superior to those NTV. A crucial feature ML2006a4 is derivatization ketoamide reactive group improves cell permeability bioavailability. Last, was found be less sensitive several cause resistance NTV ETV occur natural population. Thus, anticipatory design can preemptively address potential mechanisms expand treatment options variants.

Язык: Английский

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Drug Repurposing Using FDA Adverse Event Reporting System (FAERS) Database

Current Drug Targets, Год журнала: 2024, Номер 25(7), С. 454 - 464

Опубликована: Апрель 3, 2024

Drug repurposing is an emerging approach to reassigning existing pre-approved therapies for new indications. The FDA Adverse Event Reporting System (FAERS) a large database of over 28 million adverse event reports submitted by medical providers, patients, and drug manufacturers provides extensive safety signal data. In this review, four common strategies using FAERS are described, including inverse detection single disease, drug-drug interactions that mitigate target ADE, identifying drug-ADE pairs with opposing gene perturbation signatures congruent signatures. purpose review provide overview these different approaches successful applications in the literature. With fast expansion reports, FAERS-based represents promising strategy discovering uses therapies.

Язык: Английский

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Inhibitors of SARS-CoV-2 Main Protease (Mpro) as Anti-Coronavirus Agents

Biomolecules, Год журнала: 2024, Номер 14(7), С. 797 - 797

Опубликована: Июль 4, 2024

The main protease (Mpro) of SARS-CoV-2 is an essential enzyme that plays a critical part in the virus’s life cycle, making it significant target for developing antiviral drugs. inhibition Mpro has emerged as promising approach therapeutic agents to treat COVID-19. This review explores structure protein and analyzes progress made understanding protein–ligand interactions inhibitors. It focuses on binding kinetics, origin, chemical these provides in-depth analysis recent clinical trials involving covalent non-covalent inhibitors emerging dual targeting Mpro. By integrating findings from literature ongoing trials, this captures current state research into inhibitors, offering comprehensive challenges directions their future development anti-coronavirus agents. information new insights inspiration medicinal chemists, paving way more effective novel COVID-19 therapies.

Язык: Английский

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Efficacy and safety of GST-HG171 in adult patients with mild to moderate COVID-19: a randomised, double-blind, placebo-controlled phase 2/3 trial

EClinicalMedicine, Год журнала: 2024, Номер 71, С. 102582 - 102582

Опубликована: Апрель 10, 2024

GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed evaluate the safety of administered plus Ritonavir patients with coronavirus disease 2019 (COVID-19) infected emerging XBB non-XBB variants.

Язык: Английский

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Real‐world effectiveness and safety of oral azvudine versus nirmatrelvir‒ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 16, 2025

Azvudine and nirmatrelvir-ritonavir (Paxlovid) were widely used to treat patients with COVID-19 in China during the Omicron wave. However, efficacy safety of azvudine versus Paxlovid are poorly established. This study included 40,876 hospitalized from eleven hospitals Henan Xinjiang Provinces, China. Clinical outcomes compared between two drugs via Kaplan-Meier analysis Cox regression models. Additionally, vitro vivo experiments evaluate antitumor effects both drugs. Single-cell RNA sequencing was performed elucidate tumor immune landscape after treatment. After propensity score matching, 2404 1202 recipients Province included. revealed that related an 18% lower risk all-cause death than (95% CI: 0.676-0.987), not obviously different composite disease progression. The robustness findings verified by cohort three sensitivity analyses. Fewer adverse events observed group. Subgroup provided greater benefits for malignant tumors, significantly reducing (hazard ratio [HR]: 0.33, 95% 0.20-0.54) progression (HR: 0.54, 0.33-0.88). Furthermore, can suppress growth hepatocellular carcinoma (HCC) regulating CD4+ T CD8+ cells vivo. These suggest therapy is inferior has fewer effects. Notably, may offer clinical benefit HCC.

Язык: Английский

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Predicting the hub interactome of COVID-19 and oral squamous cell carcinoma: uncovering ALDH-mediated Wnt/β-catenin pathway activation via salivary inflammatory proteins

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 3, 2025

Язык: Английский

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Ensitrelvir for the Treatment of Nonhospitalized Adults with COVID-19: Results from the SCORPIO-HR, Phase 3, Randomized, Double-blind, Placebo-Controlled Trial

Clinical Infectious Diseases, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Ensitrelvir, a severe acute respiratory syndrome coronavirus-2 main protease inhibitor, has demonstrated clinical and virologic efficacy in previous studies. In this global phase 3 trial, nonhospitalized adults with mild-to-moderate coronavirus disease 2019 (COVID-19) symptom onset within 5 days were randomized (1:1) to receive once-daily ensitrelvir (375 mg day 1, 125 2-5) or blinded matching placebo. The primary endpoint was the restricted mean time sustained (≥2 days) resolution of 15 COVID-19 symptoms, recorded participant daily diaries, through 29 participants starting treatment after onset. Virologic safety assessed. Of 2093 participants, 1888 started Mean 12.5 13.1 placebo, respectively (difference, -0.6 days; 95% confidence interval, -1.38 0.19; P = .14). On 4, reduced least-squares RNA by 0.72 log10 copies/mL more than placebo (95% 0.55-0.90). Among those positive viral cultures at enrollment, 274/287 (95.5%) ensitrelvir-treated versus 210/280 (75.0%) placebo-treated had negative on 4. rebound similar (<1.5%) between groups. proportion ≥1 adverse event (61.5%) (60.6%). No treatment-related serious events deaths occurred. Three (0.3%) 1 (0.1%) COVID-19-related hospitalizations 29. Despite evidence antiviral activity ensitrelvir, trial did not demonstrate significant difference resolution.

Язык: Английский

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