Nanocarbon-Based Glycoconjugates as Multivalent Inhibitors of Ebola Virus Infection

Rodríguez‐Pérez, Laura; Ramos‐Soriano, Javier; Pérez‐Sánchez, Alfonso; Illescas, Beatriz M.; Muñoz, Antonio; Luczkowiak, Joanna; Lasala, Fátima; Rojo, Javier; Delgado, Rafaël; Martín, Nazario

doi:10.1021/jacs.8b03847

Cited by 65 publications

(51 citation statements)

References 100 publications

(58 reference statements)

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“…Graphene can disrupt the C-terminal domain interface of VP40 hexamers being crucial in forming the Ebola viral matrix, suggesting that graphene or similar NPs-based solutions used as a disinfectant could notably reduce the spread of the disease and prevent an Ebola epidemic (Gc et al 2017). Rodriguez-Perez et al (2018) found that MWCNTs functionalized with glycofullerenes can be considered as potent inhibitors of Ebola infection. In two mRNA vaccines based on the EBOV envelope glycoprotein, differing by the nature of signal peptide for improved glycoprotein posttranslational translocation, the mRNAs were formulated with LNPs to facilitate delivery.…”

Section: Ebola and Marburg Virusmentioning

confidence: 99%

Nanoformulations: A Valuable Tool in the Therapy of Viral Diseases Attacking Humans and Animals

Jampílek

Kráľová

2019

Nanotheranostics

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Various viruses can be considered as one of the most frequent causes of human diseases, from mild illnesses to really serious sicknesses that end fatally. Numerous viruses are also pathogenic to animals and plants, and many of them, mutating, become pathogenic also to humans. Several cases of affecting humans by originally animal viruses have been confirmed. Viral infections cause significant morbidity and mortality in humans, the increase of which is caused by general immunosuppression of the world population, changes in climate, and overall globalization. In spite of the fact that the pharmaceutical industry pays great attention to human viral infections, many of clinically used antivirals demonstrate also increased toxicity against human cells, limited bioavailability, and thus, not entirely suitable therapeutic profile. In addition, due to resistance, a combination of antivirals is needed for life-threatening infections. Thus, the development of new antiviral agents is of great importance for the control of virus spread. On the other hand, the discovery and development of structurally new antivirals represent risks. Therefore, another strategy is being developed, namely the reformulation of existing antivirals into nanoformulations and investigation of various metal and metalloid nanoparticles with respect to their diagnostic, prophylactic, and therapeutic antiviral applications. This chapter is focused on nanoscale materials/formulations with the potential to be used for the treatment or inhibition of the spread of viral diseases caused by human immunodeficiency virus, influenza A viruses (subtypes H3N2 and H1N1), avian influenza and swine influenza viruses, respiratory syncytial virus, herpes simplex virus, hepatitis B and C viruses, Ebola and Marburg viruses, Newcastle disease virus, dengue and Zika viruses, and pseudorabies virus. Effective antiviral long-lasting and target-selective nanoformulations developed for oral, intravenous, intramuscular, intranasal, intrarectal, intravaginal, and intradermal applications are discussed.

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Section: Ebola and Marburg Virusmentioning

confidence: 99%

Nanoformulations: A Valuable Tool in the Therapy of Viral Diseases Attacking Humans and Animals

Jampílek

Kráľová

2019

Nanotheranostics

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“…An increasing number of antiviral nanomaterials have been developed by interfering with the interaction between virus and its associated cell receptor to achieve broad-spectrum efficacy. 14,15 Heparan sulfate proteoglycans (HSPGs) are reported to act as receptors of many viruses, such as dengue virus, human cytomegalovirus (HCMV), human immunodeciency virus (HIV), respiratory syncytial virus (RSV), herpes simplex virus (HSV), loviruses and human papillomavirus (HPV). 16 Heparan sulfates (HS), an important constituent of HSPG, are structurally similar to heparin.…”

Section: Introductionmentioning

confidence: 99%

High antiviral activity of mercaptoethane sulfonate functionalized Te/BSA nanostars against arterivirus and coronavirus

et al. 2020

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“…[23] With this background, inhibition of DC-SIGN-mediated attachment of viral particles to innate immune cells represents a promising strategy for the development of antiviral drugs. [24][25][26] In the past, this strategy has been investigated for the treatment of HIV, [20] ebola, [27] zika, [28] and dengue infections. [28] In view of the recent emergence of the SARS-CoV-2 pandemic, DC-SIGN-targeted antivirals could represent a promising host-directed treatment option for COVID-19.…”

Section: Introductionmentioning

confidence: 99%

“…This mechanism leads to an increase in apparent binding affinity of protein-carbohydrate interactions of up to a factor of 10 6 . [32,33] In this context, functionalized polymeric supports, [34] peptides, [35] dendrimers, [36] nanoparticles, [37] fullerenes, [28] carbon nanotubes, [27] and thiacalixarenes [38] have been studied. However, a severe drawback of some of these nonbiodegradable multivalent scaffolds is their potential accumulation and associated toxicity, especially when prolonged pulmonary applications are considered.…”

Section: Introductionmentioning

confidence: 99%

Poly-L-lysine Glycoconjugates Inhibit DC-SIGN-mediated Attachment of Pandemic Viruses

Cramer¹,

Aliu²,

Jiang³

et al. 2020

Preprint

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Envelope glycoproteins of many viruses are heavily glycosylated. Among other functions, virus glycans can mediate interactions with host receptors and contribute to internalization and virus dissemination. The C-type lectin receptor DC-SIGN, which is expressed by cells of the innate immune system, can act as an entry receptor for pathogens, including pandemic viruses such as SARS-CoV-2, ebola, and HIV. In the context of the recent SARS-CoV-2 pandemic, this mechanism has been linked to severe cases of COVID-19. Inhibition of the interaction between DC-SIGN and viral envelope glycoproteins has therefore the potential to generate broad spectrum antivirulent agents. Moreover, the important role of this mechanism in numerous viral infections, as well as an interaction partner conserved in the host genome highlight the potential of DC-SIGN-targeted therapeutics not only for the treatment of existing infections, but also for the rapid response to future pandemics with newly emerging virus serotypes. Here, we demonstrate that mannose-functionalized poly-L-lysine glycoconjugates efficiently inhibit the attachment of viral glycoproteins from SARS-CoV-2, ebola, and HIV to DC-SIGN-presenting cells with up to picomolar affinity. Treatment of susceptible cells leads to prolonged receptor internalization and statistically significant inhibition of virus binding for up to 6 h. Furthermore, the polymers are fully biocompatible and readily cleared by the target cells. Finally, the thermodynamic analysis of these multivalent interactions revealed an entropy-driven affinity enhancement, opening promising perspectives for the future development of multivalent therapeutics.

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Nanocarbon-Based Glycoconjugates as Multivalent Inhibitors of Ebola Virus Infection

Cited by 65 publications

References 100 publications

Nanoformulations: A Valuable Tool in the Therapy of Viral Diseases Attacking Humans and Animals

Nanoformulations: A Valuable Tool in the Therapy of Viral Diseases Attacking Humans and Animals

High antiviral activity of mercaptoethane sulfonate functionalized Te/BSA nanostars against arterivirus and coronavirus

Poly-L-lysine Glycoconjugates Inhibit DC-SIGN-mediated Attachment of Pandemic Viruses

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