The Potential of Peptide-Based Inhibitors in Disrupting Protein–Protein Interactions for Targeted Cancer Therapy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3117 - 3117

Published: March 28, 2025

Protein-protein interactions (PPIs) form an intricate cellular network known as the interactome, which is essential for various processes, such gene regulation, signal transduction, and metabolic pathways. The dysregulation of this has been closely linked to disease states. In cancer, these aberrant PPIs, termed oncogenic PPIs (OncoPPIs), are involved in tumour formation proliferation. Therefore, inhibition OncoPPIs becomes a strategy targeted cancer therapy. Small molecule inhibitors have dominant PPI owing their small size ability cross cell membranes. However, peptide-based emerged compelling alternatives, offering distinct advantages over inhibitors. Peptides, with larger flexible backbones, can effectively engage broad interfaces PPIs. Their high specificity, lower toxicity, ease modification make them promising candidates Over past decade, significant advancements made developing This review discusses critical aspects targeting emphasizes significance therapy, explores using therapeutic agents. It also highlights recent progress peptide design aimed at overcoming limitations therapeutics, comprehensive overview current landscape potential treatment.

Language: Английский

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Paxlovid for nonhospitalized patients with COVID‐19

Academic Emergency Medicine, Journal Year: 2024, Volume and Issue: 31(6), P. 621 - 623

Published: March 22, 2024

The authors declare no conflicts of interest.

Language: Английский

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Antiviral properties of milk proteins and peptides against SARS-COV-2: A review

Journal of Functional Foods, Journal Year: 2024, Volume and Issue: 117, P. 106237 - 106237

Published: May 15, 2024

Certain milk proteins and peptides exhibit promising immunogenic antiviral properties, particularly against coronaviruses like SARS-CoV-2. Amidst the global pandemic, these bioactive components present potential alternatives for combating viral diseases. Milk are known to play important roles functioning in various stages of SARS-CoV-2 replication cycle, including entry, endocytic processes, replication, cell signaling modulation. Notably, bovine lactoferrin, is reported synergistically enhance effects remdesivir, an FDA-approved anti-SARS-CoV-2 drug. Peptides derived from have demonstrated some efficacy both vitro silico studies. While findings highlight as natural agents, further validation through vivo studies clinical trials imperative determine their efficacy, safety, optimal dosages. This review provides a comprehensive exploration specific peptides.

Language: Английский

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Clinical rebound after treatment with nirmatrelvir/ritonavir in COVID-19

BMC Infectious Diseases, Journal Year: 2024, Volume and Issue: 24(1)

Published: Sept. 12, 2024

Language: Английский

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Differences in COVID-19 Outpatient Antiviral Treatment Among Adults Aged ≥65 Years by Age Group — National Patient-Centered Clinical Research Network, United States, April 2022–September 2023

MMWR Morbidity and Mortality Weekly Report, Journal Year: 2024, Volume and Issue: 73(39), P. 876 - 882

Published: Oct. 3, 2024

Adults aged ≥65 years experience the highest risk for COVID-19-related hospitalization and death, with increasing age; outpatient antiviral treatment reduces these severe outcomes. Despite proven benefit of COVID-19 treatment, information on differences in use among older adults by age group is limited. Nonhospitalized patients during April 2022-September 2023 were identified from National Patient-Centered Clinical Research Network. Differences 65-74, 75-89, ≥90 assessed. Multivariable logistic regression was used to estimate association between nonreceipt treatment. Among 393,390 persons years, 45.9% received antivirals, including 48.4%, 43.5%, 35.2% those 65-75, 76-89, respectively. Patients 75-89 had 1.17 (95% CI = 1.15-1.19) 1.54 1.49-1.61) times adjusted odds being untreated, respectively, compared 65-74 years. 12,543 outcomes, 2,648 (21.1%) an medication, 177,874 (46.7%) 380,847 without Antiviral underutilized years; oldest are least likely receive To prevent COVID-19-associated morbidity mortality, increased medications needed.

Language: Английский

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COVID-19 Therapeutics for Nonhospitalized Older Adults

JAMA, Journal Year: 2024, Volume and Issue: 332(18), P. 1511 - 1511

Published: Oct. 7, 2024

This Viewpoint summarizes the factors contributing to increased risk of severe outcomes and hospitalization associated with COVID-19 among older adults, stresses importance assessing before infection occurs, calls for all immunocompromised adults be considered treatment, details 3 recommended therapies.

Language: Английский

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Virologic Response and Safety of Ibuzatrelvir, a Novel SARS-CoV-2 Antiviral, in Adults With COVID-19

Clinical Infectious Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Abstract Background Despite effective vaccines and treatments for COVID-19, clinical burden persists. An unmet need exists additional agents with safety profiles allowing use across a broad population. Ibuzatrelvir is an orally bioavailable SARS-CoV-2 Mpro inhibitor demonstrated in vitro antiviral activity low potential concerns, including drug–drug interactions. Methods This phase 2b, double-blind, randomized trial enrolled US adults aged 18 to <65 years symptomatic COVID-19 no risk factors severe disease. Participants were 1:1:2:2 receive 100, 300, or 600 mg ibuzatrelvir placebo twice daily 5 days. Nasopharyngeal specimens collected on days 1 (baseline), 3, 5, 10, 14, 21; adverse events (AEs) recorded through day 33. The primary end point was change RNA level (viral load [VL]) from baseline among participants VL ≥4 log10 copies/mL. Results Of 240 enrollees, 237 received ≥1 dose; 199 included the analysis. Placebo-adjusted least squares mean (80% confidence interval) (log10 copies/mL) at significant all doses: 100 mg, ‒0.7 (‒1.1 ‒0.3) copies/mL, P = .02; 300 ‒0.8 (‒1.3 ‒0.3), .01; ‒1.2 (‒1.5 ‒0.8), < .0001. AEs occurred similar percentages of groups. No deaths any cause treatment-related serious 33, reported dysgeusia. Conclusions All 3 doses associated robust acceptable profile, supporting continued development. Clinical Trials Registration NCT05799495.

Language: Английский

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Viral SARS-CoV-2 Rebound Rates in Linked Commercial Pharmacy-Based Testing and Health Care Claims

Open Forum Infectious Diseases, Journal Year: 2024, Volume and Issue: 11(6)

Published: April 29, 2024

Abstract Background Viral SARS-CoV-2 rebound (viral RNA rebound) is challenging to characterize in large cohorts due the logistics of collecting frequent and regular diagnostic test results. Pharmacy-based testing data provide an opportunity study phenomenon a population, also enabling subgroup analyses. The current real-world evidence approach complements approaches focused on smaller, prospective designs. Methods We linked real-time reverse transcription quantitative polymerase chain reaction from national pharmacy-based health care claims via tokenization calculate cumulative incidence viral within 28 days following positive results nirmatrelvir/ritonavir (NMV-r)–treated untreated individuals during Omicron era (December 2021–November 2022) prior (October 2020–November 2021). Results Among 30 646 patients, rate was 3.5% (95% CI, 2.0%–5.7%) NMV-r–treated infections as compared with 1.5% 1.3%–1.7%) 1.9% 1.7%–2.1%) era. patients who were vaccinated (n = 8151), high risk 4411), or older (≥65 years, n 4411) occurred at comparable rates overall cohort (range, 1.1%–4.8%). rebounds levels 8% 5% 11% infections. Rates hospitalization between (0%) (0%–1.2%). Conclusions Our findings suggest rare (< 5%), that consistent those EPIC-HR trial (Evaluation Protease Inhibition for COVID-19 High-Risk Patients). Most occurrences associated low levels, progression severe disease not observed.

Language: Английский

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COVID-19 clinical rebound after treatment with nirmatrelvir/ritonavir

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 21, 2024

Background: Nirmatrelvir/ritonavir (NM/r) is a safe and effective oral antiviral therapeutic used for treatment of mild-to-moderate COVID-19. Case reports described clinical rebound syndrome whereby individuals experience relapse symptoms shortly after completing successful treatment. There lack information on frequency COVID-19 NM/r in routine care, contributing factors, outcomes. Methods: We reviewed electronic medical records to verify diagnosis, symptoms, with from January-June 2022. defined as clear improvement followed by recurrence or worsening within 30 days five-day course NM/r. Results: studied 268 adults median age 57 (IQR 47, 68), 80% White race, 85% non-Hispanic ethnicity, 55% female, vaccinated boosted against SARS-CoV-2, 68% any co-morbidity. Sixteen (6.0%) patients were determined have rebound. The time starting was 11 9, 13). Notable demographic factors higher proportion (not statistically significant) among female sex (75% vs 54.5% no rebound), Black race (12.5% 4.9% presence at least one co-morbidity (81.3% 67.5% prior SARS-CoV-2 infection (100% 92.9% rebound). Only patient (6.25%) hospitalized Conclusions: mild favorable outcomes more common than previously reported real-world care studies.

Language: Английский

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EFFECTS OF ANTIVIRAL THERAPEUTIC DRUGS FOR SARS-COV-2 ON TREATMENT OUTCOMES AND CLINICAL PARAMETERS

Eurasian Journal of Ecology, Journal Year: 2024, Volume and Issue: 79(2), P. 136 - 146

Published: Jan. 1, 2024

The emergence of SARS-CoV-2, the virus responsible for COVID-19 pandemic, has prompted extensive research into antiviral therapeutic interventions aimed at improving treatment outcomes and clinical parameters. It provides a concise overview conducted in this field, focusing on impact significance various drugs. By analyzing key studies trials, it aims to elucidate efficacy safety profiles drugs such as remdesivir, favipiravir, molnupiravir, Paxlovid managing COVID-19. scientific practical lies its contribution understanding role combating SARS-CoV-2 infection. This knowledge is crucial optimizing strategies patient during ongoing pandemic. Methodologically, involves reviewing synthesizing data from reputable published peer-reviewed journals. Key parameters assessed include viral clearance, mortality rates, hospitalization duration, adverse effects associated with drug administration. main results analysis highlight varying impacts different outcomes. For instance, remdesivir shows promise reducing recovery time mortality, while favipiravir demonstrates enhanced clearance but may cause transient liver enzyme elevations. In conclusion, underscores value mitigating findings contribute evolving offer insights care protocols. these informing healthcare professionals policymakers about effective options cases, ultimately abstract encapsulates essential aspects emphasizing scientific, practical, methodological advancing our response global

Language: Английский

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