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Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
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Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...
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Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
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Viral Structure00:56

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Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
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Related Experiment Video

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Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
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Oxadiazepinone HBV capsid assembly modulators.

Scott D Kuduk1, Bart Stoops2, Angela M Lam1

  • 1Novira Therapeutics, A Janssen Pharmaceuticals Company, 1400 McKean Road, Spring House, PA 19477, United States.

Bioorganic & Medicinal Chemistry Letters
|September 7, 2021
PubMed
Summary
This summary is machine-generated.

Researchers developed new Hepatitis B virus (HBV) capsid assembly modulators (CAMs) by optimizing a pyrazolo piperidine series into advanced oxadiazepinones, targeting persistent HBV infection.

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Area of Science:

  • Hepatology
  • Virology
  • Medicinal Chemistry

Background:

  • The Hepatitis B virus (HBV) core protein is crucial for viral replication and persistence, making it a key drug target.
  • Small molecule capsid assembly modulators (CAMs) have shown promise in clinical trials for treating chronic HBV infection by targeting HBV capsid assembly.

Purpose of the Study:

  • To describe the development and structure-activity relationship (SAR) of a novel series of HBV CAMs.
  • To evolve a pyrazolo piperidine lead series into advanced oxadiazepinone HBV CAMs for potential therapeutic use.

Main Methods:

  • Medicinal chemistry optimization of a pyrazolo piperidine lead series.
  • Structure-activity relationship (SAR) studies to guide the development of new compounds.
  • Synthesis and evaluation of novel oxadiazepinone derivatives as HBV CAMs.

Main Results:

  • Successful evolution of the pyrazolo piperidine lead series into a novel oxadiazepinone scaffold.
  • Identification of advanced HBV CAMs with potential for modulating HBV capsid assembly.

Conclusions:

  • The novel oxadiazepinone series represents a promising advancement in the development of HBV CAMs.
  • These compounds offer a potential new therapeutic strategy for managing chronic Hepatitis B virus infection.