Human Colostrum and Derived Extracellular Vesicles Prevent Infection by Human Rotavirus and Respiratory Syncytial Virus in Vitro

2021 ◽  
Vol 37 (1) ◽  
pp. 122-134
Author(s):  
Andrea Civra ◽  
Rachele Francese ◽  
Manuela Donalisio ◽  
Paola Tonetto ◽  
Alessandra Coscia ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antiviral Activity ◽  
Human Milk ◽  
Extracellular Vesicles ◽  
Respiratory Infections ◽  
Extracellular Vesicle ◽  
Cross Sectional ◽  
Human Colostrum ◽  
Syncytial Virus

Background It is known that breastfeeding protects the infant from enteric and respiratory infections; however, the antiviral properties of human milk against enteric and respiratory viruses are largely unexplored. Research aims To explore the antiviral activity of human preterm colostrum against rotavirus and respiratory syncytial virus and to assess whether the derived extracellular vesicle contribute to this activity. Methods We used a cross-sectional, prospective two-group non-experimental design. Colostra were collected from mothers of preterm newborns ( N = 10) and extracellular vesicles were purified and characterized. The antiviral activity of colostra and derived extracellular vesicles were tested in vitro against rotavirus and respiratory syncytial virus and the step of viral replication inhibited by extracellular vesicles was investigated. Results Each sample of colostrum and colostrum-derived extracellular vesicles had significant antiviral activity with a wide interpersonal variability. Mechanism of action studies demonstrated that extracellular vesicles acted by interfering with the early steps of the viral replicative cycle. Conclusion We demonstrated the intrinsic antiviral activity of human colostrum against rotavirus and respiratory syncytial virus and we showed that extracellular vesicles substantially contribute to the overall protective effect. Our results contribute to unravelling novel mechanisms underlying the functional role of human milk as a protective and therapeutic agent in preterm infants.

scholarly journals Mitoxantrone Shows In Vitro, but Not In Vivo Antiviral Activity against Human Respiratory Syncytial Virus

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1176
Author(s):  
Patricia G. de la Sota ◽  
Elena Lorente ◽  
Laura Notario ◽  
Carmen Mir ◽  
Oscar Zaragoza ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Infections ◽  
The Elderly ◽  
Human Respiratory Syncytial Virus ◽  
Mice Model ◽  
Drug Candidates ◽  
Antiviral Activities ◽  
Syncytial Virus

Human respiratory syncytial virus (HRSV) is the most common cause of severe respiratory infections in infants and young children, often leading to hospitalization. In addition, this virus poses a serious health risk in immunocompromised individuals and the elderly. HRSV is also a major nosocomial hazard in healthcare service units for patients of all ages. Therefore, the development of antiviral treatments against HRSV is a global health priority. In this study, mitoxantrone, a synthetic anthraquinone with previously reported in vitro antiprotozoal and antiviral activities, inhibits HRSV replication in vitro, but not in vivo in a mice model. These results have implications for preclinical studies of some drug candidates.

scholarly journals Respiratory syncytial virus prevalence in children admitted to five Kenyan district hospitals: a cross-sectional study

2019 ◽  
Vol 3 (1) ◽  
pp. e000409
Author(s):  
Jacqueline Le Geyt ◽  
Stephanie Hauck ◽  
Mark Lee ◽  
Jennifer Mackintosh ◽  
Jessica Slater ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Infections ◽  
Cross Sectional Study ◽  
Single Centre ◽  
Cross Sectional ◽  
Virus Prevalence ◽  
District Hospitals ◽  
Positive Rate ◽  
Rsv Infection ◽  
Syncytial Virus

Acute respiratory infections (ARIs) are a leading cause of under-five mortality globally. In Kenya, the reported prevalence of respiratory syncytial virus (RSV) infections in single-centre studies has varied widely. Our study sought to determine the prevalence of RSV infection in children admitted with ARI fulfilling the WHO criteria for bronchiolitis. This was a prospective cross-sectional prevalence study in five hospitals across central and highland Kenya from April to June 2015. Two hundred and thirty-four participants were enrolled. The overall RSV positive rate was 8.1%, which is lower than in previous Kenyan studies. RSV-positive cases were on average 5 months younger than RSV-negative cases.

scholarly journals Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans

2016 ◽  
Vol 196 (6) ◽  
pp. 2699-2710 ◽  
Author(s):  
Silke M. Currie ◽  
Emily Gwyer Findlay ◽  
Amanda J. McFarlane ◽  
Paul M. Fitch ◽  
Bettina Böttcher ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antiviral Activity ◽  
Protective Function ◽  
Syncytial Virus

Antiviral activity of diarylheptanoid stereoisomers against respiratory syncytial virus in vitro and in vivo

2013 ◽  
Vol 67 (4) ◽  
pp. 773-781 ◽  
Author(s):  
Katsuhiko Konno ◽  
Motofumi Miura ◽  
Masaharu Toriyama ◽  
Shigeyasu Motohashi ◽  
Rie Sawamura ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antiviral Activity ◽  
Syncytial Virus

scholarly journals Activity and Regulation of Alpha Interferon in Respiratory Syncytial Virus and Human Metapneumovirus Experimental Infections

2005 ◽  
Vol 79 (16) ◽  
pp. 10190-10199 ◽  
Author(s):  
Antonieta Guerrero-Plata ◽  
Samuel Baron ◽  
Joyce S. Poast ◽  
Patrick A. Adegboyega ◽  
Antonella Casola ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antiviral Activity ◽  
Respiratory Infections ◽  
Significant Degree ◽  
Inhibitory Effect ◽  
Human Metapneumovirus ◽  
Absolute Amount ◽  
Potent Inducer ◽  
Cpg Oligodeoxynucleotides ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause a similar spectrum of respiratory infections in humans. Classified within the Paramyxoviridae family, Pneumovirinae subfamily, RSV and hMPV present a significant degree of divergence in genome constellation, organization, and protein sequences. RSV has been reported to be a poor inducer of alpha/beta interferons (IFN-α/β) and partially resistant to its antiviral activity. The nature of the innate immune response to hMPV is currently unknown. Herein, an experimental mouse model was used to investigate the interplay between RSV and hMPV infections and IFN-α in the airways. RSV-infected BALB/c mice treated intranasally with either poly-ICLC, a potent inducer of IFN-α, or directly with recombinant IFN-α showed significantly reduced lung viral titers, inflammation, and clinical disease than untreated controls. However, RSV was significantly less sensitive to the antiviral activity of IFN-α than hMPV. Similarly, when the ability to directly induce IFN-α production was assessed, RSV was clearly a weaker inducer of IFN-α than hMPV, as shown by both kinetics and the absolute amount of IFN-α secreted into the bronchoalveolar lavage. To further investigate the putative inhibitory effect of these viruses on IFN-α production, mice were infected for 48 h prior to treatment with poly-ICLC or a specific Toll-like receptor 9 ligand, CpG oligodeoxynucleotides. Strikingly, both poly-ICLC- and CpG-mediated IFN-α production was abrogated by either RSV or MPV infection. These results suggest that a complex interplay between virus-specific and host-mediated responses regulates IFN-α in the lung during infection by members of the Pneumovirinae family.

scholarly journals A Druggable Pocket at the Nucleocapsid/Phosphoprotein Interaction Site of Human Respiratory Syncytial Virus

2015 ◽  
Vol 89 (21) ◽  
pp. 11129-11143 ◽  
Author(s):  
Mohamed Ouizougun-Oubari ◽  
Nelson Pereira ◽  
Bogdan Tarus ◽  
Marie Galloux ◽  
Safa Lassoued ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Inhibitory Activity ◽  
In Silico ◽  
Respiratory Infections ◽  
Structural Information ◽  
Pharmacophore Model ◽  
Ribonucleoprotein Complex ◽  
Syncytial Virus

ABSTRACTPresently, respiratory syncytial virus (RSV), the main cause of severe respiratory infections in infants, cannot be treated efficiently with antivirals. However, its RNA-dependent polymerase complex offers potential targets for RSV-specific drugs. This includes the recognition of its template, the ribonucleoprotein complex (RNP), consisting of genomic RNA encapsidated by the RSV nucleoprotein, N. This recognition proceeds via interaction between the phosphoprotein P, which is the main polymerase cofactor, and N. The determinant role of the C terminus of P, and more particularly of the last residue, F241, in RNP binding and viral RNA synthesis has been assessed previously. Here, we provide detailed structural insight into this crucial interaction for RSV polymerase activity. We solved the crystallographic structures of complexes between the N-terminal domain of N (N-NTD) and C-terminal peptides of P and characterized binding by biophysical approaches. Our results provide a rationale for the pivotal role of F241, which inserts into a well-defined N-NTD pocket. This primary binding site is completed by transient contacts with upstream P residues outside the pocket. Based on the structural information of the N-NTD:P complex, we identified inhibitors of this interaction, selected byin silicoscreening of small compounds, that efficiently bind to N and compete with Pin vitro. One of the compounds displayed inhibitory activity on RSV replication, thereby strengthening the relevance of N-NTD for structure-based design of RSV-specific antivirals.IMPORTANCERespiratory syncytial virus (RSV) is a widespread pathogen that is a leading cause of acute lower respiratory infections in infants worldwide. RSV cannot be treated efficiently with antivirals, and no vaccine is presently available, with the development of pediatric vaccines being particularly challenging. Therefore, there is a need for new therapeutic strategies that specifically target RSV. The interaction between the RSV phosphoprotein P and the ribonucleoprotein complex is critical for viral replication. In this study, we identified the main structural determinants of this interaction, and we used them to screen potential inhibitorsin silico. We found a family of molecules that were efficient competitors of Pin vitroand showed inhibitory activity on RSV replication in cellular assays. These compounds provide a basis for a pharmacophore model that must be improved but that holds promises for the design of new RSV-specific antivirals.

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