Characterisation of SARS-CoV-2 genomic variation in response to molnupiravir treatment in the AGILE Phase IIa clinical 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 Multidisciplinary Sciences

De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report

Shiv Gandhi et al.

Summary: This article reports a case of remdesivir resistance mutation in an immunocompromised patient with SARS-CoV-2 infection. The patient developed viral shedding recurrence and whole genome sequencing identified a mutation, E802D, in the nsp12 RNA-dependent RNA polymerase. In vitro experiments showed that this mutation increased remdesivir resistance but had a fitness cost in the absence of remdesivir. The patient achieved sustained clinical and virologic response with casirivimab-imdevimab treatment.

NATURE COMMUNICATIONS (2022)

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Article Infectious Diseases

Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial

Saye H. Khoo et al.

Summary: This study aimed to evaluate the efficacy and safety of molnupiravir in patients with COVID-19 who have been vaccinated or unvaccinated. The results suggest that molnupiravir might have antiviral activity against SARS-CoV-2 infection.

LANCET INFECTIOUS DISEASES (2022)

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Article Multidisciplinary Sciences

Mechanism of SARS-CoV-2 polymerase stalling by remdesivir

Goran Kokic et al.

Summary: Remdesivir is the only FDA-approved drug for treating COVID-19 patients, working by inhibiting the RNA-dependent RNA polymerase (RdRp) of coronaviruses. It hinders RNA synthesis and impairs proofreading by the viral 3'-exonuclease, leading to a stalled replication process.

NATURE COMMUNICATIONS (2021)

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Article Virology

SARS-CoV-2 whole-genome sequencing using reverse complement PCR: For easy, fast and accurate outbreak and variant analysis.

Jordy P. M. Coolen et al.

Summary: This study introduces a novel whole genome sequencing technique for monitoring the transmission and variants of SARS-CoV-2, which proved to be effective in investigating outbreak clusters and identifying new connections amidst the emergence of variants of concern.

JOURNAL OF CLINICAL VIROLOGY (2021)

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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 Multidisciplinary Sciences

Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex

Brandon Malone et al.

Summary: Backtracking, a common regulatory feature in transcription, is found in viruses as well, with evidence suggesting that SARS-CoV-2 RdRp may utilize backtracking for viral transcription and replication. The interaction between RdRp and nsp13 helicase facilitates backtracking, which may aid in proofreading and antiviral resistance for SARS-CoV-2.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (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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Article Biochemistry & Molecular Biology

Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis

Florian Kabinger et al.

Summary: Molnupiravir is an oral antiviral drug candidate that increases viral RNA mutations frequency and inhibits replication of SARS-CoV-2 by altering the substrate preference of RdRp. This two-step mutagenesis mechanism can explain the broad-spectrum antiviral activity of molnupiravir, making it a promising COVID-19 treatment option.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2021)

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Article Biology

Patterns of within-host genetic diversity in SARS-CoV-2

Gerry Tonkin-Hill et al.

Summary: The study examines within-host diversity in 1181 samples of SARS-CoV-2, finding detectable within-host mutations in 95.1% of the samples. Analysis of the mutational spectra reveals strong strand asymmetries, suggesting that damage or RNA editing may dominate the accumulation of mutations during the SARS-CoV-2 pandemic.

ELIFE (2021)

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Article Virology

Assignment of epidemiological lineages in an emerging pandemic using the pangolin tool

Aine O'Toole et al.

Summary: The global virus genomics community has responded unprecedentedly to the SARS-CoV-2 pandemic, leading to significant advances in 'real-time' generation and sharing of genomic data. The development of new analytical methods, such as pangolin, has been necessary to handle the rapid growth in virus genome data production. Pangolin has processed nearly two million virus genomes, aiding in SARS-CoV-2 genomic epidemiology and providing researchers with valuable information about the pandemic's transmission lineages.

VIRUS EVOLUTION (2021)

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Article Cell Biology