The Quest for an Efficacious Antiviral for Respiratory Syncytial Virus

Torrence, Paul F.; Powell, Linda D

doi:10.1177/095632020201300601

Cited by 15 publications

(5 citation statements)

References 214 publications

(280 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2001 the estimated cost to complete a 5-month prophylactic course with Synagis approached $5,000. There is in addition one pharmaceutical agent (ribavirin) licensed to treat acute respiratory tract disease caused by RSV [Torrence and Powell, 2002]. However, the benefits are controversial [Hall, 2001;Krilov, 2002b].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of respiratory syncytial virus infection with the CC chemokine RANTES (CCL5)

Elliott

Tebbey

Pryharski

et al. 2004

Journal of Medical Virology

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) is a major cause of respiratory tract disease in infants, aged adults, and immunosuppressed patients. The only approved medicines for RSV disease are administration of prophylatic antibodies or treatment with a synthetic nucleoside. Both approaches are expensive and the latter is not without risk and of controversial benefit. The present investigation studied whether pharmaceutical or biologic compounds based upon chemokines might be useful in preventing RSV disease. Of interest was RANTES/CCL5, which inhibits infection by HIV strains that use chemokine receptor (CCR)-5 as co-receptor. Herein, we report that prior or simultaneous treatment of HEp-2 cells with recombinant human CCL5 provides dose-dependent inhibition of infection with RSV. Other recombinant chemokines (MIP-1alpha/CCL3, MIP-1beta/CCL4, MCP-2/CCL8, eotaxin/CCL11, MIP-1delta/CCL15, stromal cell derived factor (SDF)-1alpha/CXCL12) were not inhibitory. The data suggested that CCL5 might inhibit infection by blocking fusion (F) protein-epithelial cell interactions. Infections by mutant RSV strains deleted of small hydrophobic and/or attachment proteins and only expressing F protein in the envelope were inhibited by prior treatment with CCL5 or a biologically inactive N-terminally modified met-CCL5. Inhibition was also observed when virus adsorption and treatment with CCL5 were performed at 4 degrees C. Flow cytometry further revealed that epithelial cells were positive for CCR3, but not CCR1 or CCR5. Thus, novel mimetics of CCL5 may be useful prophylatic agents to prevent respiratory tract disease caused by RSV.

show abstract

Section: Introductionmentioning

confidence: 99%

Inhibition of respiratory syncytial virus infection with the CC chemokine RANTES (CCL5)

Elliott

Tebbey

Pryharski

et al. 2004

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…Postinfection (p.i.) treatment of RSV with anti-RSV immunoglobulin shows no benefit (187), and the current need for additional effective anti-RSV agents is well acknowledged (234).…”

mentioning

confidence: 99%

Respiratory Syncytial Virus Infection: Mechanisms of Redox Control and Novel Therapeutic Opportunities

Garofalo

Kolli

Casola

2013

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

“…[2][3][4][5] Postinfection treatment of RSV with anti-RSV immune globulin shows no benefit, [6] and the current need for additional effective anti-RSV agents is well-acknowledged. [7] RSV is a member of subfamily Pneumovirinae in the family Paramyxoviridae, which are non-segmented viruses with genomes composed of a single molecule of RNA in negativesense orientation. After an RSV virion enters a cell, the genomic RNA is transcribed into 5′ capped and 3′ polyadenylated mRNAs that each code for one of the 11 individual RSV proteins [8,9].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Respiratory Syncytial Virus Infections With Morpholino Oligomers in Cell Cultures and in Mice

et al. 2008

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infants, young children, and high-risk adults. Currently, there is no vaccine to prevent RSV infection, and the available therapeutic agents are of limited utility. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) are a class of antisense agents that can enter cells readily and interfere with viral protein expression through steric blocking of complementary RNA. Two antisense PPMOs, designed to target sequence that includes the 5'-terminal region and translation start-site region of RSV L mRNA, were tested for anti-RSV activity in cultures of two human-airway cell lines. Both PPMOs showed minimal cytotoxicity and one of them, (AUG-2), reduced viral titers by >2.0 log(10). Intranasal (i.n.) treatment of BALB/c mice with AUG-2 PPMO before the RSV inoculation produced a reduction in viral titer of 1.2 log(10) in lung tissue at day 5 postinfection (p.i.), and attenuated pulmonary inflammation at day 7 postinfection. These data show that the AUG-2 PPMO possesses potent anti-RSV activity and is worthy of further investigation as a candidate for potential therapeutic application.

show abstract

The Quest for an Efficacious Antiviral for Respiratory Syncytial Virus

Cited by 15 publications

References 214 publications

Inhibition of respiratory syncytial virus infection with the CC chemokine RANTES (CCL5)

Inhibition of respiratory syncytial virus infection with the CC chemokine RANTES (CCL5)

Respiratory Syncytial Virus Infection: Mechanisms of Redox Control and Novel Therapeutic Opportunities

Inhibition of Respiratory Syncytial Virus Infections With Morpholino Oligomers in Cell Cultures and in Mice

Contact Info

Product

Resources

About