scholarly journals Synthetic mRNA expressed Cas13a mitigates RNA virus infections

2018 ◽  
Author(s):  
Swapnil S. Bawage ◽  
Pooja M. Tiwari ◽  
Philip J. Santangelo
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Nucleic Acids ◽  
Rna Virus ◽  
Virus Infections ◽  
Viral Pathogens ◽  
New Class ◽  
Syncytial Virus ◽  
Synthetic Mrna ◽  
Over Time

AbstractThe emergence of the CRISPR-Cas system as a technology has transformed our ability to modify nucleic acids. Prokaryotes evolved one member of this family, CRISPR-Cas effector, Cas13a, as an RNA-guided ribonuclease that protects them from invading bacteriophages. Here, we demonstrate that Cas13a can be programmed to target eukaryotic viral pathogens, influenza virus A (IVA) and human respiratory syncytial virus (hRSV) in human cells. We designed synthetic mRNA coding for Cas13a, which when guided by CRISPR RNAs (crRNA) to target influenza virus or hRSV RNA, significantly mitigates these infections both prophylactically, therapeutically, and over time. These data demonstrate a possible new class of synthetic mRNA-powered anti-viral interventions.One Sentence SummarycrRNA guided Cas13a halts RNA virus infections

scholarly journals A comparison of influenza and respiratory syncytial virus infections among infants admitted to hospital with acute respiratory infections

1976 ◽  
Vol 77 (3) ◽  
pp. 383-392 ◽  
Author(s):  
E. O. Caul ◽  
D. K. Waller ◽  
S. K. R. Clarke ◽  
B. D. Corner
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Rural Areas ◽  
Influenza A ◽  
Respiratory Infections ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
Syncytial Virus ◽  
One Year

SUMMARYAmong 741 children under 5 years admitted to hospital with respiratory infections during two winters, infection with influenza A virus was diagnosed in 70 (9%), with influenza B virus in 8 (1%), and with respiratory syncytial virus (RSV) in 259 (35 %). Both influenza virus and RSV infections were diagnosed most frequently in children under the age of one year, and diagnosed more frequently in males than females. Influenza illnesses were more severe in boys than girls. Both infections occurred more often, but were not more severe, in children from a conurbation than in those from ‘rural’ areas. Convulsions were the cause of 36% of admissions with influenza A infections, but were rare in RSV infections. Bronchiolitis was the reason for 39% of admissions with RSV infections, but was rare in influenza infections. It is suggested that infants admitted to hospital are a good source of influenza virus strains for monitoring arttigenic variation.

Respiratory Syncytial Virus and Influenza Virus Infections

2008 ◽  
Vol 27 (Supplement) ◽  
pp. S92-S96 ◽  
Author(s):  
Timothy P. Welliver ◽  
Jennifer L. Reed ◽  
Robert C. Welliver
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Virus Infections ◽  
Syncytial Virus

scholarly journals 4'-Fluorouridine is a broad-spectrum orally efficacious antiviral blocking respiratory syncytial virus and SARS-CoV-2 replication

2021 ◽  
Author(s):  
Julien Sourimant ◽  
Carolin Lieber ◽  
Megha Aggarwal ◽  
Robert Cox ◽  
Josef Wolf ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Broad Spectrum ◽  
Rna Virus ◽  
Oral Treatment ◽  
The Elderly ◽  
Virus Infections ◽  
Once Daily ◽  
Syncytial Virus ◽  
Well Differentiated

The COVID-19 pandemic has underscored the critical need for broad-spectrum therapeutics against respiratory viruses. Respiratory syncytial virus (RSV) is a major threat to pediatric patients and the elderly. We describe 4'-fluorouridine (4'-FlU, EIDD-2749), a ribonucleoside analog that inhibits RSV, related RNA viruses, and SARS-CoV-2 with high selectivity index in cells and well-differentiated human airway epithelia. Polymerase inhibition in in vitro RdRP assays established for RSV and SARS-CoV-2 revealed transcriptional pauses at positions i or i+3/4 post-incorporation. Once-daily oral treatment was highly efficacious at 5 mg/kg in RSV-infected mice or 20 mg/kg in ferrets infected with SARS-CoV-2 WA1/2020 or variant-of-concern (VoC) isolate CA/2020, initiated 24 or 12 hours after infection, respectively. These properties define 4'-FlU as a broad-spectrum candidate for the treatment of RSV, SARS-CoV-2 and related RNA virus infections.

scholarly journals Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 234
Author(s):  
Sarah Al-Beltagi ◽  
Cristian Alexandru Preda ◽  
Leah V. Goulding ◽  
Joe James ◽  
Juan Pu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Virus Challenge ◽  
2009 H1n1 ◽  
Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

Respiratory Syncytial Virus (RSV) Diseases

2022 ◽  
Author(s):  
Heinz-Josef Schmitt ◽  
Khrystyna Hrynkevych
Keyword(s):  
Respiratory Syncytial Virus ◽  
Rna Virus ◽  
Passive Immunization ◽  
Active Immunization ◽  
F Protein ◽  
Hospitalization Rates ◽  
Syncytial Virus ◽  
Repeated Infections ◽  
Long Acting ◽  
Underlying Diseases

The respiratory syncytial virus (RSV) is an RNA virus that causes annual ARI outbreaks during winter with mild URTI in the general population, but with severe LRTI particularly among young children (bronchiolitis), patients with underlying diseases and people >65 years of age. RSV does not induce a long-lasting protective immunity and repeated infections throughout life are the norm. Basically, all children have been infected by 2 years of age and of those hospitalized, >50% are <3 months and 75% are <6 months of age. The overall CFR is 1/500. For adults ≥65 years, RSV hospitalization rates are 90–250/105. There is no specific therapy, general preventive measures include general hygiene and isolation/separation of patients. A monoclonal anti-F-protein antibody is available for passive immunization of selected high-risk children. It requires monthly injections, comes at a high cost and has limited efficacy (50% against RSV hospitalization). Active immunization failed in the past, probably as the post-fusion conformation of the F-protein was used. Long-acting monoclonal antibodies (for infants) as well as stabilized pre-fusion F-protein vaccines (for immunization of pregnant women, children, older adults) produced on various platforms are in late stages of clinical development.

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