Lethal mutagenesis as an antiviral strategy

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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Article Biochemistry & Molecular Biology

Molnupiravir promotes SARS-CoV-2 mutagenesis via the RNA template

Calvin J. Gordon et al.

Summary: The study found that Molnupiravir or NHC can increase the mutation frequencies in replicating coronaviruses, leading to enhanced antiviral effects; NHC-TP primarily competes with CTP for incorporation, resulting in RNA mutations; Biochemical data support a mechanism of action of Molnupiravir that is primarily based on RNA mutagenesis mediated via the template strand.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

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Article Immunology

β-D-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells

Shuntai Zhou et al.

Summary: Mutagenic ribonucleosides can serve as broad-spectrum antiviral agents, but may pose risks to the host due to their host mutagenic activity in addition to antiviral activity.

JOURNAL OF INFECTIOUS DISEASES (2021)

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Article Multidisciplinary Sciences

Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model

Jean-Selim Driouich et al.

Summary: Despite limited pre-clinical evidence, repurposed drugs such as favipiravir are being extensively evaluated in clinical trials to combat the lack of antiviral options against SARS-CoV-2. Favipiravir shows strong antiviral efficacy in a Syrian hamster model, with high doses reducing viral infectivity while inducing mutations in viral genomes. However, toxicity concerns are noted at the highest tested dose, requiring further pharmacokinetic and tolerance studies before potential human use.

NATURE COMMUNICATIONS (2021)

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Article Cell Biology