Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

Article Medicine, General & Internal

Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients

A. Jayk Bernal et al.

Summary: This study found that early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Cell Biology

A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus

William A. Fischer et al.

Summary: In a clinical trial, the safety, tolerability, and antiviral efficacy of molnupiravir were evaluated in unvaccinated individuals with confirmed SARS-CoV-2 infection. The study found that participants receiving high-dose molnupiravir had a shorter time to viral RNA clearance and a lower detection rate of infectious virus. Molnupiravir was well tolerated across all doses.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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News Item Critical Care Medicine

Omicron variant and booster COVID-19 vaccines

Talha Khan Burki

LANCET RESPIRATORY MEDICINE (2022)

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Article Public, Environmental & Occupational Health

Making Statistical Sense of the Molnupiravir MOVe-OUT Clinical Trial

Kristian Thorlund et al.

Summary: This article discusses the issues and flaws in a clinical trial of an oral therapeutic drug called molnupiravir, and suggests the need for independent external trials to determine the efficacy of this drug.

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE (2022)

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Article Primary Health Care

Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial

Jienchi Dorward et al.

Summary: This study aimed to determine the effects of colchicine on recovery time and hospitalization/death related to COVID-19. The results showed that colchicine did not reduce recovery time or decrease the risk of hospitalization/death related to COVID-19 among participants in the community.

BRITISH JOURNAL OF GENERAL PRACTICE (2022)

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Article Medicine, General & Internal

Favipiravir, lopinavir-ritonavir, or combination therapy (FLARE): A randomised, double-blind, 2 x 2 factorial placebo-controlled trial of early antiviral therapy in COVID-19

David M. Lowe et al.

Summary: This study aimed to evaluate the effect of early administration of favipiravir, lopinavir-ritonavir, or both on the viral load trajectory of SARS-CoV-2. The results showed that none of the treatment regimens significantly reduced the viral load in the primary analysis. Further evaluation of favipiravir with dose escalation is needed.

PLOS MEDICINE (2022)

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Article Microbiology

Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets

Robert M. Cox et al.

Summary: Treating SARS-CoV-2-infected ferrets with nucleoside analogue MK-4482/EIDD-2801 reduced viral load and suppressed virus spread. This therapeutic approach shows promise in breaking transmission chains of the COVID-19 pandemic.

NATURE MICROBIOLOGY (2021)

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Article Microbiology

Human Safety, Tolerability, and Pharmacokinetics of Molnupiravir, a Novel Broad-Spectrum Oral Antiviral Agent with Activity against SARS-CoV-2

Wendy P. Painter et al.

Summary: Molnupiravir showed rapid appearance and dose-proportional increase in plasma, with good tolerability in healthy volunteers. The study evaluated single and multiple doses of molnupiravir and the impact of food on pharmacokinetics in subjects, showing no accumulation following multiple doses and a decrease in absorption rate when administered with food, but no decrease in overall exposure.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

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Review Pharmacology & Pharmacy

Systematic Review and Patient-Level Meta-Analysis of SARS-CoV-2 Viral Dynamics to Model Response to Antiviral Therapies

Silke Gastine et al.

Summary: A meta-analysis was conducted to study the viral dynamics of SARS-CoV-2 in humans, revealing that older age, male gender, and more severe illness are associated with longer viral clearance times. Remdesivir and interferon combined with ribavirin were found to accelerate viral clearance, suggesting further investigation into combination therapy. The study has established a viral dynamic dataset and NLME model for designing and analyzing antiviral trials.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2021)

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Article Multidisciplinary Sciences

SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801

Angela Wahl et al.

Summary: The study suggests that bats may be the source of coronaviruses that can be directly transmitted to humans. Using the LoM model, efficient replication of SARS-CoV, MERS-CoV, SARS-CoV-2, and two SARS-like bat coronaviruses in human lung tissue was demonstrated. Infection with SARS-CoV-2 predominantly targets human lung epithelial cells and induces a sustained inflammatory response. The broad-spectrum antiviral agent EIDD-2801 significantly inhibits SARS-CoV-2 replication in vivo, showing potential for prevention and treatment of COVID-19.

NATURE (2021)

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Article Medicine, General & Internal

The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model

Rana Abdelnabi et al.

Summary: The combination of Molnupiravir and Favipiravir demonstrated a significant antiviral effect in a Syrian hamster model infected with SARS-CoV-2, reducing infectious virus titers in the lungs and preventing transmission to co-housed untreated sentinels. Mutation frequency in the viral RNA recovered from the lungs of treated animals increased, with a higher frequency of C-to-T mutations observed in the combo treatment group, explaining the pronounced antiviral potency of the combination.

EBIOMEDICINE (2021)

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Article Multidisciplinary Sciences

Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model

Kyle Rosenke et al.

Summary: Orally administered nucleoside analog MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model, with an inhibitory effect observed whether the drug is given 12 hours before or 12 hours after infection. This suggests the potential of MK-4482 for controlling SARS-CoV-2 infection in humans following high-risk exposure and for treating COVID-19 patients.

NATURE COMMUNICATIONS (2021)

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Article Infectious Diseases

Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label, dose-escalating, randomized controlled study

Saye H. Khoo et al.

Summary: The study found that molnupiravir is safe and well tolerated in treating early COVID-19 patients. A dose of 800mg twice daily for 5 days was recommended for Phase II evaluation.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2021)

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Editorial Material Biochemistry & Molecular Biology

Molnupiravir: coding for catastrophe

Brandon Malone et al.

Summary: Molnupiravir disrupts the accuracy of SARS-CoV-2 genome replication and prevents viral propagation by fostering error accumulation, a process known as 'error catastrophe'.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2021)

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Article Medicine, General & Internal

Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE): protocol for a randomised, controlled, open-label, adaptive platform, trial of community treatment of COVID-19 syndromic illness in people at higher risk

Gail Hayward et al.

Summary: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE trial is an open-label, multiarm, prospective, adaptive platform, randomized clinical trial aimed at evaluating potential treatments for COVID-19. The trial includes interventions such as hydroxychloroquine, azithromycin, and doxycycline, with randomization probabilities being modified based on pre-specified interim analyses to allocate more participants to interventions with better outcomes. Ethics approval has been obtained, and the results will be disseminated to policymakers and published in peer-reviewed journals.

BMJ OPEN (2021)

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Article Critical Care Medicine

Doxycycline for community treatment of suspected COVID-19 in people at high risk of adverse outcomes in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial

Christopher C. Butler et al.

Summary: In high-risk individuals, treatment with doxycycline for COVID-19 did not result in meaningful reductions in recovery time or hospitalization/death rates related to the disease.

LANCET RESPIRATORY MEDICINE (2021)

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Article Cell Biology