4.8 Article

Structural basis for substrate selection by the SARS-CoV-2 replicase

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Biochemistry & Molecular Biology

SARS-CoV-2 RdRp uses NDPs as a substrate and is able to incorporate NHC into RNA from diphosphate form molnupiravir

Maofeng Wang et al.

Summary: The coronavirus disease 2019 has caused significant harm to global health and economy for three years. Research on the viral RNA dependent RNA polymerase (RdRp) complex reveals its potential as a target for antiviral drug development. The study found that RdRp can efficiently synthesize RNA using nucleoside diphosphates as substrates and can incorporate molnupiravir diphosphate, leading to genome mutation and virus death. The diphosphate form of molnupiravir is shown to be a better substrate for RdRp than the triphosphate form, providing a new drug design strategy.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES (2023)

Review Cell Biology

Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design

Brandon Malone et al.

Summary: The molecular basis and complexity of coronavirus RNA-synthesizing machinery is still not fully understood. Recent research has focused on deciphering and understanding the structures, functions, and interactions of the subunits involved in SARS-CoV-2 replication and transcription. Both viral and host factors play a crucial role in coordinating RNA translation, replication, and transcription, making them potential targets for antiviral therapy.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2022)

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)

Article Multidisciplinary Sciences

A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase

Ashleigh Shannon et al.

Summary: AT-527 is a promising candidate drug that targets the SARS-CoV-2 replication machinery by inhibiting the RNA-dependent RNA polymerase.

NATURE COMMUNICATIONS (2022)

Article Biochemistry & Molecular Biology

Ensemble cryo-EM reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex

James Chen et al.

Summary: In the complex of SARS-CoV-2 nsp13 helicase and RNA polymerase, a mechanism has been revealed through cryo-EM and MD simulations that controls their movement in opposite directions on RNA. This mechanism allows the helicase to drive the polymerase backward on the RNA template and switch between RNA synthesis and backtracking.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2022)

Article Cell Biology

Mutations in the SARS-CoV-2 RNA-dependent RNA polymerase confer resistance to remdesivir by distinct mechanisms

Laura J. Stevens et al.

Summary: This study identified mutations in the nonstructural protein 12 RNA-dependent RNA polymerase of the SARS-CoV-2 virus that confer resistance to the antiviral drug remdesivir. These mutations result in decreased preference for the drug as a substrate and can be transferred to other betacoronaviruses, causing replication defects and up to 38-fold resistance. The findings highlight the importance of further research to understand and prevent the emergence of remdesivir resistance mutations in clinical settings.

SCIENCE TRANSLATIONAL MEDICINE (2022)

Article Biochemistry & Molecular Biology

Cryo-EM Structure of an Extended SARS-CoV-2 Replication and Transcription Complex Reveals an Intermediate State in Cap Synthesis

Liming Yan et al.

Summary: The study presents a structural snapshot of SARS-CoV-2 RTC during mRNA transcription, revealing the interaction between nsp9 and nsp12, as well as the catalytic activity of nsp12 NiRAN. The results demonstrate an intermediate state of RTC towards mRNA synthesis, providing valuable information for antiviral drug development.
Article Multidisciplinary Sciences

Coronavirus replication-transcription complex: Vital and selective NMPylation of a conserved site in nsp9 by the NiRAN-RdRp subunit

Heiko Slanina et al.

Summary: The study reveals that coronavirus nsp12 has NMPylation activity, catalyzing the transfer of NMP to nsp9 and essential for virus replication. It also highlights the importance of the phosphoramidate active site in the NNE tripeptide sequence.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

Article Multidisciplinary Sciences

Structure of the SARS-CoV-2 RNA-dependent RNA polymerase in the presence of favipiravir-RTP

Katerina Naydenova et al.

Summary: The structure of the RNA polymerase inhibitor favipiravir bound to the SARS-CoV-2 RNA-dependent RNA polymerase has been determined, revealing its binding mode at the catalytic site. The inhibitor is weakly incorporated into the RNA primer strand, leading to suppression of RNA replication in the presence of natural nucleotides.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

Article Virology

Developing a direct acting, orally available antiviral agent in a pandemic: the evolution of molnupiravir as a potential treatment for COVID-19

George R. Painter et al.

Summary: Although vaccines are available, there is still a critical need for antiviral drugs with potent activity against SARS-CoV-2, especially for immunosuppressed individuals and emerging variants. Molnupiravir evolved from preclinical development for influenza to a potential COVID-19 treatment, with the development timeline accelerated significantly to focus on coronavirus infections. Collaboration with regulatory authorities in real time played a key role in expediting the program.

CURRENT OPINION IN VIROLOGY (2021)

Article Biology

Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective

Mona Seifert et al.

Summary: Remdesivir, the only FDA-approved drug for SARS-CoV-2, disrupts viral replication by stopping the polymerase. Through the use of magnetic tweezers, researchers have shown how remdesivir interferes with replication.
Article Biochemistry & Molecular Biology

Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication

Jack P. K. Bravo et al.

Summary: Remdesivir, a nucleoside analog approved by the US FDA for treating COVID-19, was found to delay chain termination by blocking RNA translocation on RNA-dependent RNA polymerase, providing insights for rational design of improved antiviral drugs.

MOLECULAR CELL (2021)

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)

Article Biochemical Research Methods

Expression and purification of tag-free SARS-CoV-2 RNA-dependent RNA polymerase in Escherichia coli

Tyler L. Dangerfield et al.

Summary: The protocol details the efficient production of recombinant RdRp in E. coli for screening antivirals to treat COVID-19. Despite the added complexity of multiple purification steps, the method provides greater activity, yield at lower cost, and is faster than baculovirus expression systems.

STAR PROTOCOLS (2021)

Article Biochemistry & Molecular Biology

The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus

Calvin J. Gordon et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2020)

Article Biochemistry & Molecular Biology

Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase

Quan Wang et al.

Article Multidisciplinary Sciences

Structure of replicating SARS-CoV-2 polymerase

Hauke S. Hillen et al.

NATURE (2020)

Article Medicine, General & Internal

Remdesivir for the Treatment of Covid-19-Final Report

John H. Beigel et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Article Biochemical Research Methods

Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstruction

Ali Punjani et al.

NATURE METHODS (2020)

Article Biochemical Research Methods

MetaUniDec: High-Throughput Deconvolution of Native Mass Spectra

Deseree J. Reid et al.

JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY (2019)

Article Multidisciplinary Sciences

Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors

Robert N. Kirchdoerfer et al.

NATURE COMMUNICATIONS (2019)

Article Medicine, General & Internal

A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics

Sabue Mulangu et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

Article Biochemical Research Methods

New tools for the analysis and validation of cryo-EM maps and atomic models

Pavel V. Afonine et al.

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY (2018)

Letter Biochemical Research Methods

MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy

Shawn Q. Zheng et al.

NATURE METHODS (2017)

Article Biochemical Research Methods

cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination

Ali Punjani et al.

NATURE METHODS (2017)

Article Biochemical Research Methods

Addressing preferred specimen orientation in single-particle cryo-EM through tilting

Yong Zi Tan et al.

NATURE METHODS (2017)

Article Multidisciplinary Sciences

Structural basis of viral RNA-dependent RNA polymerase catalysis and translocation

Bo Shu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

Article Multidisciplinary Sciences

Structural basis for RNA replication by the hepatitis C virus polymerase

Todd C. Appleby et al.

SCIENCE (2015)

Article Biochemistry & Molecular Biology

One number does not fit all: Mapping local variations in resolution in cryo-EM reconstructions

Giovanni Cardone et al.

JOURNAL OF STRUCTURAL BIOLOGY (2013)

Editorial Material Biology

Collaboration gets the most out of software

Andrew Morin et al.

Article Biochemical Research Methods

MolProbity: all-atom structure validation for macromolecular crystallography

Vincent B. Chen et al.

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY (2010)

Article Biochemistry & Molecular Biology

Structural insights into mechanisms of catalysis and inhibition in Norwalk virus polymerase

Dmitry F. Zamyatkin et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2008)

Review Biochemistry & Molecular Biology

Making and breaking nucleic acids:: Two-Mg2+-ion catalysis and substrate specificity

W Yang et al.

MOLECULAR CELL (2006)

Article Biochemistry & Molecular Biology

Automated molecular microscopy: The new Leginon system

C Suloway et al.

JOURNAL OF STRUCTURAL BIOLOGY (2005)

Article Biochemistry & Molecular Biology

Structural basis for substrate selection by T7 RNA polymerase

D Temiakov et al.

Article Biochemical Research Methods

Coot:: model-building tools for molecular graphics

P Emsley et al.

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY (2004)

Article Chemistry, Multidisciplinary

UCSF chimera - A visualization system for exploratory research and analysis

EF Pettersen et al.

JOURNAL OF COMPUTATIONAL CHEMISTRY (2004)

Review Biochemistry & Molecular Biology

A structural and primary sequence comparison of the viral RNA-dependent RNA polymerases

JA Bruenn

NUCLEIC ACIDS RESEARCH (2003)