skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Programmable icosahedral shell system for virus trapping
Broad-spectrum antiviral platforms that can decrease or inhibit viral infection would alleviate many threats to global public health. Nonetheless, effective technologies of this kind are still not available. Here, we describe a programmable icosahedral canvas for the self-assembly of icosahedral shells that have viral trapping and antiviral properties. Programmable triangular building blocks constructed from DNA assemble with high yield into various shell objects with user-defined geometries and apertures. We have created shells with molecular masses ranging from 43 to 925 MDa (8 to 180 subunits) and with internal cavity diameters of up to 280 nm. The shell interior can be functionalized with virus-specific moieties in a modular fashion. We demonstrate this virus-trapping concept by engulfing hepatitis B virus core particles and adeno-associated viruses. We demonstrate the inhibition of hepatitis B virus core interactions with surfaces in vitro and the neutralization of infectious adeno-associated viruses exposed to human cells.  more » « less
Award ID(s):
2011846
PAR ID:
10506781
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ;
Publisher / Repository:
Nature Portfolio
Date Published:
Journal Name:
Nature Materials
Volume:
20
Issue:
9
ISSN:
1476-1122
Page Range / eLocation ID:
1281 to 1289
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; (, Frontiers in Physics)
    null (Ed.)
    Pathogenic viruses cause many human, animal, and plant diseases that are associated with substantial morbidity, mortality and socio-economic impact. Although effective strategies for combatting virus transmission and associated disease are available, global outbreaks of viral pathogens such as the virus responsible for the COVID-19 pandemic demonstrate that there is still a critical need for new approaches that can be used to interrupt the chain of viral infection and mitigate virus-associated pathogenesis. Recent studies point to non-thermal plasma (NTP), a partly ionized gas comprised of a complex mixture of reactive oxygen and nitrogen species along with physical effectors, as the potential foundation for new antiviral approaches. A more thorough understanding of the antiviral properties and safety of NTP has stimulated explorations of NTP as the basis for treatments of viral diseases. The recently described immunomodulatory properties of NTP are also being evaluated for potential use in immunotherapies of viral diseases as well as in antiviral vaccination strategies. In this review, we present the current state-of-the-art in addition to compelling arguments that NTP merits further exploration for use in the prevention and management of viral infections and associated diseases. 
    more » « less
  2. ; ; ; ; (, International Journal of Biomathematics)
    Direct-acting antiviral agents (DAAs) are known to interfere with various intracellular stages of the hepatitis C virus (HCV) life cycle and have demonstrated efficacy in treating HCV infection. However, DAA monotherapy can lead to drug resistance due to mutations. This paper explores the impact of DAA therapy on HCV dynamics using a multiscale age-structured partial differential equation (PDE) model that incorporates intracellular viral RNA replication within infected cells and two strains of viruses representing a drug-sensitive strain and a drug-resistant mutant variant, respectively. We derived an equivalent ordinary differential equation (ODE) model from the PDE model to simplify mathematical analysis and numerical simulations. We studied the dynamics of the two virus strains before treatment and investigated the impact of mutations on the evolution kinetics of drug-sensitive and drug-resistant viruses, as well as the competition between the two strains during treatment. We also explored the role of DAAs in blocking HCV RNA replication and releasing new virus particles from cells. During treatment, mutations do not significantly influence the dynamics of various virus strains; however, they can generate low-level HCV that may be completely inhibited due to their poor fitness. The fitness of the mutant strain compared to the drug-sensitive strain determines which strain dominates the virus population. We also investigated the prevalence and drug resistance evolution of HCV variants during DAA treatment. 
    more » « less
  3. ; ; ; ; ; ; ; ; ; (, International Journal of Molecular Sciences)
    The emergence and mutation of pathogenic viruses have been occurring at an unprecedented rate in recent decades. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global public health crisis due to extensive viral transmission. In situ RNA mapping has revealed angiotensin-converting enzyme 2 (ACE2) expression to be highest in the nose and lower in the lung, pointing to nasal susceptibility as a predominant route for infection and the cause of subsequent pulmonary effects. By blocking viral attachment and entry at the nasal airway using a cyclodextrin-based formulation, a preventative therapy can be developed to reduce viral infection at the site of entry. Here, we assess the safety and antiviral efficacy of cyclodextrin-based formulations. From these studies, hydroxypropyl beta-cyclodextrin (HPBCD) and hydroxypropyl gamma-cyclodextrin (HPGCD) were then further evaluated for antiviral effects using SARS-CoV-2 pseudotypes. Efficacy findings were confirmed with SARS-CoV-2 Delta variant infection of Calu-3 cells and using a K18-hACE2 murine model. Intranasal pre-treatment with HPBCD-based formulations reduced viral load and inflammatory signaling in the lung. In vitro efficacy studies were further conducted using lentiviruses, murine hepatitis virus (MHV), and influenza A virus subtype H1N1. These findings suggest HPBCD may be used as an agnostic barrier against transmissible pathogens, including but not limited to SARS-CoV-2. 
    more » « less
  4. ; ; (, Studies in Applied Mathematics)
    Abstract Recent experimental evidence suggests that spatial heterogeneity plays an important role in within‐host infections caused by different viruses including hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). To examine the spatial effects of viral infections, in this paper we study the asymptotic spreading in a within‐host viral infection model, which describes the spatial expansion speeds of viruses and infected cells within an infected host. We first establish the boundedness of solutions to the Cauchy problem via local ‐estimates and dual arguments. Then the spreading speed is estimated when the basic reproduction number of the corresponding kinetic system is larger than one. More precisely, the upper bounds of the spreading speed are given by constructing suitable upper solutions while the lower bounds of the spreading speed are obtained by introducing an auxiliary equation with nonlocal delay. When the basic reproduction number of the corresponding kinetic system is less than or equal to one, the virus dies out uniformly. Finally, we present some numerical simulations to illustrate our theoretical findings and discuss the biological relevance of these results. 
    more » « less
  5. ; ; (, Bulletin of Mathematical Biology)
    Abstract Analyzing the impact of the adaptive immune response during acute hepatitis B virus (HBV) infection is essential for understanding disease progression and control. Here we developed mathematical models of HBV infection which either lack terms for adaptive immune responses, or assume adaptive immune responses in the form of cytolytic immune killing, non-cytolytic immune cure, or non-cytolytic-mediated block of viral production. We validated the model that does not include immune responses against temporal serum hepatitis B DNA (sHBV) and temporal serum hepatitis B surface-antigen (HBsAg) experimental data from mice engrafted with human hepatocytes (HEP). Moreover, we validated the immune models against sHBV and HBsAg experimental data from mice engrafted with HEP and human immune system (HEP/HIS). As expected, the model that does not include adaptive immune responses matches the observed high sHBV and HBsAg concentrations in all HEP mice. By contrast, while all immune response models predict reduction in sHBV and HBsAg concentrations in HEP/HIS mice, the Akaike Information Criterion cannot discriminate between non-cytolytic cure (resulting in a class of cells refractory to reinfection) and antiviral block functions (of up to$$99\%$$ 99 % viral production 1–3 weeks following peak viral load). We can, however, reject cytolytic killing, as it can only match the sHBV and HBsAg data when we predict unrealistic levels of hepatocyte loss. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email