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Viral Structure00:56

Viral Structure

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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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Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
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Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
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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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Viruses are unique biological entities that blur the boundary between living and non-living systems. Although they lack cellular structure and metabolic processes, they can exhibit characteristics of life when infecting a host. Their defining feature is a nucleic acid core, composed of either DNA or RNA, encapsulated within a protein coat called a capsid. This simple structure allows them to invade host cells and use their machinery for replication efficiently.Viral Structure and...
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Related Experiment Video

Updated: Jan 15, 2026

Nucleocapsid Annealing-Mediated Electrophoresis NAME Assay Allows the Rapid Identification of HIV-1 Nucleocapsid Inhibitors
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Delineating Structural Functionalities of Lenacapavir Amenable to Modifications for Targeting Emerging Drug-Resistant

Daniel Adu-Ampratwum1, Arun S Annamalai2, Tung Dinh2

  • 1Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.

ACS Medicinal Chemistry Letters
|October 15, 2025
PubMed
Summary

Lenacapavir is a novel HIV-1 capsid inhibitor for multidrug-resistant infections. A new analog, KFA-027, shows improved activity against emerging resistant mutations like M66I.

Keywords:
GS-6207HIV-1Lenacapavir (LEN)antiretroviral therapycapsiddrug-resistant mutationsfirst-in-classinhibitorlong-actingresistance-associated-mutations (RAMs)structure−activity relationship (SAR) study

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Area of Science:

  • Virology
  • Medicinal Chemistry
  • Drug Discovery

Background:

  • Lenacapavir (LEN) is a first-in-class, long-acting HIV-1 capsid inhibitor for multidrug-resistant HIV-1.
  • LEN offers a vital treatment option for heavily treatment-experienced adults but has a low barrier to resistance.
  • Emerging resistance, particularly the M66I variant, necessitates the development of next-generation inhibitors.

Purpose of the Study:

  • To identify structural modifications of LEN to overcome resistance.
  • To develop LEN analogs with enhanced antiviral activity against LEN-resistant HIV-1 variants, specifically M66I.

Main Methods:

  • Structure-based drug design to identify modification sites on LEN.
  • Synthesis and characterization of novel LEN analogs.
  • Antiviral assays to evaluate activity against wild-type (WT) and M66I mutant HIV-1.

Main Results:

  • A new LEN analog, KFA-027, was developed.
  • KFA-027 demonstrated significantly improved antiviral activity against the M66I variant (EC50 ~ 444 nM, >20-fold increase compared to LEN).
  • The findings highlight a promising strategy for next-generation capsid inhibitors.

Conclusions:

  • KFA-027 represents a promising next-generation inhibitor effective against LEN-resistant HIV-1 M66I mutation.
  • This work provides a roadmap for developing novel capsid inhibitors to combat emerging drug resistance in HIV-1 treatment.
  • Continued research into LEN analogs is crucial for sustained efficacy against evolving HIV-1 strains.