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Related Concept Videos

Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
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Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), are enveloped viruses characterized by their single-stranded, positive-sense RNA genome and helical nucleocapsid structure. The hallmark of these viruses is their club-shaped spike (S) glycoproteins that protrude from the viral envelope, facilitating attachment to host cells. Typically, coronaviruses infect the upper respiratory tract, often causing mild or asymptomatic disease. However, certain strains like...
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Human respiratory syncytial virus (RSV) is a widespread pathogen that primarily targets infants and young children but also poses a serious health risk to elderly and immunocompromised individuals. Belonging to the Pneumoviridae family, RSV is a negative-sense, single-stranded RNA virus within the Pneumovirus genus. Its global health burden is significant, with millions of cases annually resulting in hospitalizations and mortality, particularly in resource-limited settings. Although most...
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Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
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Related Experiment Video

Updated: Jun 15, 2026

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
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Variant-proof high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways.

Matthew Gagne1, Barbara J Flynn1, Christopher Cole Honeycutt1

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A novel protein, RBD-62, effectively suppressed SARS-CoV-2 Delta variant replication in macaques. This variant-agnostic therapeutic agent prevented severe disease without hindering immune responses, offering a promising approach against evolving viruses.

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Area of Science:

  • Virology
  • Immunology
  • Biomedical Engineering

Background:

  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) evolves rapidly, developing mutations that confer resistance to vaccines, prior infection immunity, and antiviral medications.
  • The emergence of new SARS-CoV-2 variants necessitates the development of variant-agnostic therapeutic agents that can maintain efficacy against diverse viral strains and avoid exerting selective pressure.
  • A therapeutic agent that prevents severe disease without promoting viral resistance would be a significant advancement in managing the ongoing pandemic.

Purpose of the Study:

  • To evaluate the efficacy of aerosolized RBD-62, a protein engineered for enhanced binding to the SARS-CoV-2 receptor-binding domain (RBD), in preventing severe disease caused by the Delta variant.
  • To assess whether RBD-62 treatment impacts the development of virus-specific T- and B-cell responses or elicits anti-drug immunity.
  • To demonstrate proof-of-concept for RBD-62 as a potential therapeutic intervention against highly virulent SARS-CoV-2 variants.

Main Methods:

  • Male rhesus macaques were challenged with the SARS-CoV-2 Delta variant, a highly pathogenic strain.
  • At the time of challenge, macaques were treated with aerosolized RBD-62, a protein with a 1000-fold enhanced ACE2 binding affinity compared to the wild-type RBD.
  • Virus replication was assessed in both upper and lower airways, and virus-specific T- and B-cell responses were monitored. Anti-drug immunity was also evaluated.

Main Results:

  • Aerosolized RBD-62 treatment effectively suppressed SARS-CoV-2 Delta variant replication in both the upper and lower airways of macaques.
  • This suppression of viral replication was observed to be equivalent across both airway compartments, a finding not previously documented with clinically approved vaccines.
  • Importantly, RBD-62 treatment did not impede the development of virus-specific T- and B-cell responses and did not induce anti-drug immunity in the treated animals.

Conclusions:

  • RBD-62 demonstrates significant potential as a variant-agnostic therapeutic agent against SARS-CoV-2.
  • The ability of RBD-62 to suppress replication without compromising host immune responses or inducing drug resistance is a key advantage.
  • These findings provide strong preclinical evidence supporting the development of RBD-62 for preventing severe COVID-19, even in the face of emerging viral variants.