FDA approved fluorine-containing drugs in 2023

Chinese Chemical Letters, Journal Year: 2024, Volume and Issue: 35(11), P. 109780 - 109780

Published: March 15, 2024

Language: Английский

---

The Design, Synthesis and Mechanism of Action of Paxlovid, a Protease Inhibitor Drug Combination for the Treatment of COVID-19

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(2), P. 217 - 217

Published: Feb. 2, 2024

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented an enormous challenge to health care systems and medicine. As a result of global research efforts aimed at preventing effectively treating SARS-CoV-2 infection, vaccines with fundamentally new mechanisms action some small-molecule antiviral drugs targeting key proteins in the viral cycle have been developed. most effective drug approved date for treatment is PaxlovidTM, which combination two protease inhibitors, nirmatrelvir ritonavir. Nirmatrelvir reversible covalent peptidomimetic inhibitor main (Mpro) SARS-CoV-2, enzyme plays crucial role reproduction. In this combination, ritonavir serves as pharmacokinetic enhancer, it irreversibly inhibits cytochrome CYP3A4 responsible rapid metabolism nirmatrelvir, thereby increasing half-life bioavailability nirmatrelvir. tutorial review, we summarize development pharmaceutical chemistry aspects Paxlovid, covering evolution warhead design, synthesis mechanism well its inhibition mechanism. efficacy Paxlovid novel virus mutants also overviewed.

Language: Английский

---

Real-world Plasma Exposure of Nirmatrelvir/Ritonavir in Chinese Hospitalized Patients With COVID-19: A Multicenter Retrospective Study

Therapeutic Drug Monitoring, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Nirmatrelvir/ritonavir is licensed for the treatment of mild-to-moderate coronavirus disease (COVID-19) in patients at an increased risk progression to severe disease. However, data on real-world plasma exposure nirmatrelvir/ritonavir remain limited, particularly Chinese patients. This study aimed assess trough concentration (Ctrough) and identify its critical factors hospitalized treated with 300 mg/100 mg twice daily over a 5-day course. A high-performance liquid chromatography-tandem mass spectrometry assay was developed validated measure Ctrough. Correlation analyses were performed variables influencing Among 110 patients, 100% had concentrations above antiviral vitro 90% effective concentration. The median Ctrough nirmatrelvir 4.55 mcg/mL (15.6× concentration), ranging from 0.65 12.44 mcg/mL. Nirmatrelvir normal mild renal impairment cohorts comparable (4.09 ± 1.97 4.57 2.21 mcg/mL) but significantly moderate cohort (6.41 2.31 mcg/mL). Sex, age, obesity not associated exposure. high COVID-19, therapeutic drug monitoring should be routinely recommended, except impairment.

Language: Английский

---

A patent review of CYP3A4 inhibitors (2018 - present)

Expert Opinion on Therapeutic Patents, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Introduction Cytochrome P450 3A4 (CYP3A4), one of the most important xenobiotic-metabolizing enzymes, plays a central role in drug metabolism and acts as key mediator drug-drug interactions. CYP3A4 inhibitors can potentiate vivo therapeutic effects CYP3A4-substrate drugs via enhancing their systematic exposure levels. Two (ritonavir cobicistat) have already been approved for modulating levels drugs.

Language: Английский

---

Lessons for Medical Countermeasure Development from Unforeseen Outbreaks

Emerging Microbes & Infections, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

The unanticipated emergence of the COVID-19 pandemic and rapid spread mpox epidemic in 2022 2024 brought unforeseen challenges to public health. While distinct nature, these outbreaks share some similarities offer valuable insights into responding novel virus dissemination vulnerable populations. In light two experiences, we aim discern prioritization medical countermeasures (MCM) among antivirals, antibodies vaccines.

Language: Английский

---

Efficacy and Safety of Sotrovimab Versus Oral Antiviral for Early Treatment in High-Risk Patients in Omicron Era: A Multicenter Retrospective Study

Pathogens, Journal Year: 2025, Volume and Issue: 14(3), P. 216 - 216

Published: Feb. 22, 2025

Introduction: High-risk patients with COVID-19 benefit from early treatment to prevent severe outcomes. Sotrovimab, a monoclonal antibody, and oral antivirals such as nirmatrelvir/ritonavir molnupiravir have been used for intervention, but their comparative efficacy safety, particularly during the Omicron-dominant phase, require further evaluation. Methods: A multicenter, retrospective study performed in southern Italy including all adult who received antiviral (sotrovimab or nirmatrelvir/r molnupiravir) between January 2022 February 2024 (omicron phase). Demographic, clinical, treatment-related data were analyzed assess primary endpoints of 28-day mortality hospitalization. Logistic regression models identified predictors key Results: total 668 high-risk treated sotrovimab (n = 326) 342: 69 273 nirmatrelvir/ritonavir) included. There was no significant difference groups (0.8% vs. 1.8% antivirals; p 0.679). However, exhibited longer median time SARS-CoV-2 negativization (13 11 days; 0.008) higher non–COVID-19-related hospitalizations (2.45% 0%; 0.003). Multivariable analysis cardiovascular cerebrovascular diseases sole predictor prolonged viral positivity (OR 1.585, 95% CI 1.072–2.345; 0.021). Additionally, immunocompromised status 16.929, 1.835–156.170; 0.013) chronic non-COVID-19 oxygen therapy 10.714, 1.623–70.725; 0.014) strongly associated mortality. Conclusions: Sotrovimab demonstrated similar preventing hospitalization among patients. Patient-specific factors, comorbidities immunosuppression, significantly influenced outcomes should guide choices.

Language: Английский

---

Real-World Experience with the Available Outpatient COVID-19 THErapies in Patients with canceR (CO.THER)

Cancers, Journal Year: 2025, Volume and Issue: 17(6), P. 999 - 999

Published: March 17, 2025

Background/Objectives: Cancer represents an important risk factor for acquiring severe acute respiratory syndrome by Coronavirus-2 (SARS-CoV-2) and subsequent hospitalization. The utility of early antiviral therapies, including their protective effect on long COVID outcomes, in cancer patients has not yet been clearly demonstrated. We conducted the CO.THER study (COVID-19 THErapies with canceR) to address this knowledge gap. Methods: designed ambispective single-center cohort study. collected clinical oncological data from hospital’s electronic patient records at start COVID-19 therapy (T0), seven days after T0 (T1), two weeks (T2), one month (T3), three months (T4), six (T5), twelve (T6). primary endpoint was rate hospitalization disease within 14 using anti-SARS-CoV-2 therapies. proportion hospitalizations (primary endpoint) computed together its exact binomial 95% confidence interval (95%CI). Results: 131 patients’ (53M [40.5%], 78F, [59.5%]; median age 62.45, interquartile range [IQR] 56–71) were enrolled. As shown Kaplan–Meier hospitalization-free estimate, only (2.1%) hospitalized a related cause starting treatment (95%CI 0.5–6.6%). cumulative survival probability beyond 12 98% 93–99%). Twelve (9.2%) reported another infection during follow-up they all retreated Nirmatrelvir–Ritonavir. reinfection-free 90% 83–95%). Further, 15 123 evaluable 3 (median 51 years, IQR 40–68) symptoms (12.2%, 95%CI 7.0–19.3%). Conclusions: Our demonstrate low reassuring safety high-risk subjects.

Language: Английский

---

Nirmatrelvir-Ritonavir Significantly Reduces Severe COVID-19 Outcomes in Diverse Taiwanese Populations: Comprehensive Evidence from a Large-Scale Longitudinal Cohort Study in Taiwan

Journal of Infection and Public Health, Journal Year: 2025, Volume and Issue: unknown, P. 102760 - 102760

Published: March 1, 2025

Nirmatrelvir-Ritonavir (NR) has proven effective for mild to moderate COVID-19 patients at risk of disease progression. Following its emergency use authorization in Taiwan January 2022, this study aims evaluate impact on severe outcomes across different patient demographics Taiwan. We performed a retrospective analysis database that includes data from three hospitals Northern Patients with 2022 were paired by propensity score matching based NR prescription. Cox proportional hazard regression calculated ratios (HR), adjusting confounding factors. Subgroup determined HRs characteristics. Among 95,096 patients, 3329 the group, and 12,807 non-NR group. users demonstrated significantly better prevention outcomes: intubation (HR=0.296 [95 % CI: 0.187-0.469], p = 0.0482); ICU admission (HR=0.327[0.108-0.991], < 0.001); mortality (HR=0.195 [0.101-0.378], 0.001). revealed lower risks among both sexes, aged 18-65 or ≥ 65 years, BMI 30, diabetes mellitus (DM), cardiovascular (CVD), chronic obstructive pulmonary (COPD). was males, 30. Mortality DM, CVD, COPD. reduces COVID-19, particularly older adults those pre-existing conditions, supporting as an essential treatment high-risk patients.

Language: Английский

---

Antivirals in COVID‐19: A Focus on Pediatric Cardiac Patients

Canadian Journal of Infectious Diseases and Medical Microbiology, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

The COVID‐19 pandemic created an unprecedented public health crisis, driven by its rapid global spread and the urgent need for worldwide collaborative interventions to contain it. This urgency spurred search therapeutic agents prevent or manage infection. Among these, various types of antivirals emerged as a prominent treatment option, supported wealth observational studies randomized controlled trials. results from such conflict, with some concluding efficacy others lack thereof, variability also occurring depending on severity in studied population. In addition, many have been explored using trials—the gold standard evaluating intervention—to only limited degree, most evidence behind their use concluded studies. Thus, sheer volume data has made it challenging resolve inconsistencies determine true efficacy. Furthermore, there is paucity literature regarding pediatric population infected COVID‐19, being extrapolated done adult patients. As such, additional trials are needed solidify effectiveness managing particularly underexplored especially vulnerable cardiac Therefore, utilizing trials, this narrative review evaluates rationale antivirals, summarizes findings literature, concludes focused discussion application

Language: Английский

---

Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections

Viruses, Journal Year: 2024, Volume and Issue: 16(4), P. 651 - 651

Published: April 22, 2024

Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC50, CC50) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios reported unbound peak plasma concentrations, (Cmax)/EC50, were used to predict the potential vivo efficacy. The 20 with highest ratios retested human Calu-3 Caco-2 cells, their CC50 was determined an expanded panel cell lines. Many inactive Antivirals controlled trials had Cmax/EC50 ≥ 6.8 or EC50 nucleoside analogs dependent. This approach earlier availability more relevant cultures could reduced number unwarranted trials.

Language: Английский

---