Perceived Risk for Severe COVID-19 and Oral Antiviral Use Among Antiviral-Eligible US Adults DOI Creative Commons
Kate Penrose, Avantika Srivastava, Yanhan Shen

и другие.

Infectious Diseases and Therapy, Год журнала: 2024, Номер 13(8), С. 1743 - 1757

Опубликована: Июнь 23, 2024

Oral antiviral medications are important tools for preventing severe COVID-19 outcomes. However, their uptake remains low reasons that not entirely understood. Our study aimed to assess the association between perceived risk outcomes and oral use among those who were eligible treatment based on Centers Disease Control Prevention (CDC) guidelines. We surveyed 4034 non-institutionalized US adults in April 2023, report findings from 934 antiviral-eligible participants with at least one confirmed SARS-CoV-2 infection since December 1, 2021 no current long COVID symptoms. Survey weights used yield nationally representative estimates. The primary exposure of interest was whether themselves be "at high COVID-19." outcome a within 5 days suspected infection. Only 18.5% considered 16.8% 15.9% took antivirals any time or infection, respectively. In contrast, 79.8% aware treatments COVID-19. Perceived high-risk status associated being more likely (adjusted prevalence ratio [aPR]: 1.11 [95% confidence interval (CI) 1.03–1.20]), prescribed (aPR 1.47 CI 1.08–2.01]), take 1.61 1.16–2.24]) 1.72 1.23–2.40]). Despite widespread awareness availability antivirals, than 80% did receive them. suggest differences actual (based CDC guidelines) may partially explain this uptake.

Язык: Английский

Computer-aided drug design of novel nirmatrelvir analogs inhibiting main protease of Coronavirus SARS-CoV-2 DOI Open Access
Kateryna Lohachova,

Anastasiia S . Sviatenko,

Alexander Kyrychenko

и другие.

Journal of Applied Pharmaceutical Science, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

A computer-aided drug design of new derivatives nirmatrelvir, an orally active inhibitor the main-protease (Mpro) severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), was performed to identify its analogues with a higher antiviral potency. The following workflow used: first, evolutionary library composed 1,866 generated starting from parent nirmatrelvir scaffold and going through small mutation, fitness scoring, ranking, selection. Second, preprocessed filtered against 3-D pharmacophore model built X-ray structure in co-crystalized complex Mpro enzyme, allowing us reduce chemical space 32 analogues. Third, structure-based molecular docking two different enzyme structures further ranked these candidates, so that up eight better-binding analogs were identified. selected hit-analogues target enzymes SARS-CoV-2 binding affinity than nirmatrelvir. main structural modifications increase overall inhibitory are identified at azabicyclo[3.1.0] hexane 2-oxopyrrolidine fragments. characteristic feature centre is similar location trifluoroacetylamino fragment, which observed for most hit-analogues. suggested rational noncovalent inhibitors based on approved drugs promising, extremely low-cost, time-efficient approach development potential pharmaceutical ingredients treatment Disease 2019.

Язык: Английский

Процитировано

6
Comparison of azvudine, molnupiravir, and nirmatrelvir/ritonavir in adult patients with mild-to-moderate COVID-19: a retrospective cohort study DOI Creative Commons
Meiping Chen,

Dixuan Jiang,

Jiaxi Rang

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Фев. 9, 2024

Abstract This study aimed to explore the effectiveness and safety of azvudine, nirmatrelvir/ritonavir, molnupiravir in adult patients with mild-to-moderate COVID-19. retrospective cohort included COVID-19 (asymptomatic, mild, common types) at First Hospital Changsha (Hunan Province, China) between March November 2022. Eligible were classified into or groups according antiviral agents they received. The outcomes times nucleic acid negative conversion (NANC). 157 treated azvudine (n = 66), nirmatrelvir/ritonavir 25). There no statistically significant differences time from diagnosis NANC among molnupiravir, [median, 9 (95% CI 9–11) vs. 11 10–12) 8–12) days, P 0.15], administration 8–10) 10 9.48–11) 8.708 7.51–11) 0.50], hospital stay 11–13) 13 12–14) 12 10–14) 0.14], even after adjustment for sex, age, type, comorbidities, Ct level, treatment, number symptoms. cumulative rates 15.2%/12.3%/16.0% day 5 ( 0.858), 34.8%/21.5%/32.0% 7 0.226), 66.7%/52.3%/60.0% days 0.246), 86.4%/86.2%/80.0% 14 0.721). No serious adverse events reported. Azvudine may be comparable regarding NANC, stay, AEs.

Язык: Английский

Процитировано

5
Effectiveness of nirmatrelvir/ritonavir and molnupiravir in non-hospitalized adults with COVID-19: systematic review and meta-analysis of observational studies DOI Creative Commons
Yonatan Moges Mesfin, Joseph E. Blais, Kelemu Tilahun Kibret

и другие.

Journal of Antimicrobial Chemotherapy, Год журнала: 2024, Номер 79(9), С. 2119 - 2131

Опубликована: Май 31, 2024

To determine the effectiveness of nirmatrelvir/ritonavir and molnupiravir among vaccinated unvaccinated non-hospitalized adults with COVID-19.

Язык: Английский

Процитировано

5
Effectiveness of Oral Nirmatrelvir/Ritonavir vs. Intravenous Three-Day Remdesivir in Preventing Progression to Severe COVID-19: A Single-Center, Prospective, Comparative, Real-Life Study DOI Creative Commons
Dimitrios Basoulis,

Aristeidis Tsakanikas,

Aikaterini Gkoufa

и другие.

Viruses, Год журнала: 2023, Номер 15(7), С. 1515 - 1515

Опубликована: Июль 7, 2023

Background: Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce. Methods: Prospective, observational study conducted a tertiary care hospital, from 1 January 2022 until 15 March 2023, during prevalence Omicron variant. Inverse probability treatment weighting (IPTW) was used to account differences between groups. Results: We included 521, mainly (56%), our analysis; 356 (68.3%) received 3RDV 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) met primary end-point at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r 5/165, 3%, p = 1). On IPTW-adjusted univariable analysis, choice did affect outcomes. In multivariable logistic regression we found that one (OR 0.26, 95%CI 0.07–0.99, 0.049) two 0.06, 0.01–0.55, 0.014) vaccine booster shots reduced risk adverse Conclusion: patient population high-risk, immunocompromised, vaccinated variant, were equally effective prevention death.

Язык: Английский

Процитировано

11
Effectiveness of nirmatrelvir‐ritonavir on severe outcomes of COVID‐19 in the era of vaccination and Omicron: An updated meta‐analysis DOI Creative Commons
Sien Ombelet, Diego Castanares‐Zapatero, Fabian Desimpel

и другие.

Journal of Medical Virology, Год журнала: 2024, Номер 96(2)

Опубликована: Фев. 1, 2024

Abstract Nirmatrelvir‐ritonavir (NR) was approved to treat SARS‐CoV‐2 positive outpatients at high risk of progression severe disease, based on a randomized trial in unvaccinated patients. Effectiveness vaccinated patients and against Omicron has not yet been confirmed by clinical data, but recent meta‐analysis suggested good real‐world effectiveness 12 studies. We updated this searching Medline Embase databases for studies assessing NR mortality, hospitalization, composite outcome hospitalization and/or death, published between October 1, 2022 May 22, 2023. Random effects subgroup analysis performed. A total 32 were included the meta‐analysis. Pooled RR effect disease 0.36 (95% confidence interval [CI]: 0.25−0.52), 0.43 (CI: 0.37−0.51), 0.52 0.45−0.61) 0.54 0.41−0.73), respectively. indicated lower mortality (RR: 0.55, CI: 0.45−0.68), similar or 0.52, 0.58, 0.66, respectively). This robustly confirms protective COVID‐19 outcomes.

Язык: Английский

Процитировано

4
Safety and Effectiveness of Nirmatrelvir-Ritonavir in Patients With Advanced Kidney Dysfunction and COVID-19 DOI
Marimar Contreras Nieves, Shuchi Anand, I‐Chun Thomas

и другие.

American Journal of Kidney Diseases, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2 DOI Creative Commons

Larysa V. Yevsieieva,

Kateryna Lohachova, Alexander Kyrychenko

и другие.

RSC Advances, Год журнала: 2023, Номер 13(50), С. 35500 - 35524

Опубликована: Янв. 1, 2023

The pandemic caused by the coronavirus SARS-CoV-2 led to a global crisis in world healthcare system. Despite some progress creation of antiviral vaccines and mass vaccination population, number patients continues grow because spread new mutations. There is an urgent need for direct-acting drugs capable suppressing or stopping main mechanisms reproduction SARS-CoV-2. Several studies have shown that successful replication virus cell requires proteolytic cleavage protein structures virus. Two proteases are crucial replicating other coronaviruses: protease (Mpro) papain-like (PLpro). In this review, we summarize essential viral proteins required its life cycle as targets chemotherapy infection provide critical summary development against COVID-19 from drug repurposing strategy up molecular design novel covalent non-covalent agents inhibiting replication. We overview choice Mpro PLpro promising pharmacological impact on cycle.

Язык: Английский

Процитировано

10
Viral Rebound After Antiviral Treatment: A Mathematical Modeling Study of the Role of Antiviral Mechanism of Action DOI

A. Chiarelli,

Hana M. Dobrovolny

Interdisciplinary Sciences Computational Life Sciences, Год журнала: 2024, Номер 16(4), С. 844 - 853

Опубликована: Июль 21, 2024

Язык: Английский

Процитировано

3
Phase I study, and dosing regimen selection for a pivotal COVID-19 trial of GST-HG171 DOI
H Zhang, Jing Zhou, Hong Chen

и другие.

Antimicrobial Agents and Chemotherapy, Год журнала: 2023, Номер 68(1)

Опубликована: Дек. 15, 2023

This study is aimed to evaluate the safety, tolerability, and pharmacokinetics (PK), as well select an appropriate dosing regimen for pivotal clinical trial of GST-HG171, orally bioavailable, potent, selective 3CL protease inhibitor by a randomized, double-blind, placebo-controlled phase I in healthy subjects. We conducted Ph1 involving 78 subjects assess PK single ascending doses (150-900 mg) multiple (MADs) (150 300 GST-HG171. Additionally, we examined food effect drug-drug interaction GST-HG171 combination with ritonavir through MAD GST-HG171/ritonavir (BID or TID) 5 days. Throughout course these studies, no serious AEs deaths occurred, necessitated discontinuation. observed that had significant impact on exposure However, presence substantially increased which facilitated selection dose (150/100 mg BID) subsequent II/III trials. The selected was achieved concentrations continuously at 6.2-9.9-fold above levels required protein-binding adjusted 50% inhibition (IC50) viral replication

Язык: Английский

Процитировано

9
Low Prevalence of Nirmatrelvir-Ritonavir Resistance-Associated Mutations in SARS-CoV-2 Lineages From Botswana DOI Creative Commons
Wonderful T. Choga, Ontlametse T. Bareng, Natasha O. Moraka

и другие.

Open Forum Infectious Diseases, Год журнала: 2024, Номер 11(7)

Опубликована: Июнь 28, 2024

We evaluated naturally occurring nirmatrelvir-ritonavir (NTV/r) resistance-associated mutations (RAMs) among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from Botswana, a country with no NTV/r use to date, in order recommend the usage of agent for high-risk patients disease 2019 (COVID-19).

Язык: Английский

Процитировано

2