Structure-Guided Improvement of a Dual HPIV3/RSV Fusion Inhibitor

Human parainfluenza virus 3 (HPIV3) and respiratory syncytial virus (RSV) are leading causes of lower respiratory tract infections. There are currently no vaccines or antiviral therapeutics to treat existing HPIV3 or RSV infections. We recently reported a peptide (VIQKI), derived from the C-terminal heptad repeat (HRC) domain of the HPIV3 fusion (F) glycoprotein that inhibits infection by both HPIV3 and RSV. The dual inhibitory activity of VIQKI is due to its unique ability to bind to the N-terminal heptad repeat (HRN) domains of both HPIV3 and RSV F, thereby preventing the native HRN-HRC interactions required for viral entry. Here we describe the structure-guided design of dual inhibitors of HPIV3 and RSV fusion with improved efficacy. We show that VIQKI derivatives possessing one (I456F) or two (I454F/I456F) phenylalanine substitutions near the N-terminus exhibit more stable assemblies with RSV HRN domain and enhanced antiviral efficacy against both HPIV3 and RSV infection. Co-crystal structures of the new Phe-substituted inhibitors co-assembled with HPIV3 or RSV HRN domains reveal that the I456F substitution makes intimate hydrophobic contact with the core trimers of both HPIV3 and RSV F.

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Reappraisal of respiratory syncytial virus as an aetiology of severe acute lower respiratory tract infections in children younger than 5 years in Nigeria

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/trz026 ◽

2019 ◽

Vol 113 (8) ◽

pp. 446-452

Author(s):

Damilola M Oladele ◽

Dimeji P Oladele ◽

Rasheedat M Ibraheem ◽

Mohammed B Abdulkadir ◽

Rasaki Adewole Raheem ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Preventive Strategy ◽

Lower Respiratory Tract Infections ◽

Cross Sectional ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections

Abstract Background Acute lower respiratory tract infections (ALRIs) especially severe ALRIs, constitute a global high burden of morbidity and mortality in children <5 y of age and respiratory syncytial virus (RSV) has been documented to a play a major aetiological role. However, Nigerian reports on severe childhood RSV ALRIs are rare and most reports are old. With recent advances in RSV preventive strategy, arises the need for a recent appraisal of RSV infection in children with severe ALRI. The current study thus set out to determine the prevalence of RSV infection among hospitalized children <5 y of age and describe the related social determinants. Methods We performed a descriptive cross-sectional study conducted over 1 y of 120 children, ages 2–59 months, diagnosed with ALRI. Relevant data were obtained and an antigen detection assay was used for viral studies. Results The prevalence of RSV infection was 34.2% and its peak was in the rainy months. The proportion of infants in the RSV-positive group was significantly higher than that in the RSV-negative group (82.9% vs 54.4%; p=0.002). These findings were largely consistent with those of earlier reports. Conclusions RSV has remained a common cause of severe ALRI in infants, especially during the rainy months in Nigeria. It is thus suggested that more effort be focused towards implementing the current global recommendations for the prevention of RSV-associated LRI, particularly in infants.

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738. Role of Respiratory Syncytial Virus and Mycoplasma pneumoniae in Pediatric Community-Acquired Lower Respiratory Tract Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.745 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S265-S265

Author(s):

Sanchit Kumar ◽

Anita Chakravarti ◽

Surinder Kumar ◽

Seema Kapoor

Keyword(s):

Respiratory Tract ◽

Predictive Value ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Rt Pcr ◽

Lower Respiratory Tract Infections ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections

Abstract Background Respiratory syncytial virus (RSV) infection is a major cause of serious lower respiratory disease in infancy and early childhood and Mycoplasma pneumoniae (M. pneumoniae) is a common cause of respiratory tract infections in all age groups. This study was conducted to determine the role of RSV and M. pneumoniae and in pediatric lower respiratory tract infections employing serological tests, polymerase chain reaction (PCR) and reverse transcriptase PCR analysis. Methods In this prospective study, 75 children aged 1 month to 5 years with acute lower respiratory tract infections (LRTIs) were investigated. Paired serum samples were obtained on admission and after 4–6 weeks to assay for M. pneumonia antibodies. Nasopharyngeal aspirates were obtained for the detection of RSV antigen by using the immunochromatographic test, reverse transcriptase-polymerase chain reaction (RT-PCR) for RSV and M. pneumoniae by PCR. Results RSV infection was positive in 20(60.60%) children aged <1 year and 13 (39.40%) aged 2–5 years, the difference being statistically insignificant (P = 0.360). M. pneumoniae infection was documented in a 15(57.6%) children aged <1 year age and 11(42.4%) in age 2–5 years which was statistically significant(P = 0.026). Clinical and radiological features among RSV and M. pnemoniae positive and negative cases were comparable. Thirty (40%) children were positive for RSV antigen and by RT-PCR and 3(12%) only by RT-PCR. Serological evidence of M pneumoniae infection was documented in 24(32%) children. M. pnemoniae PCR was positive in 8 (10.66%) patients. Together, serology and PCR detected M. pneumoniae in 26(34.66%) children. Considering RT-PCR as a diagnostic standard, the sensitivity of RSV antigen by immunochromatography was 90.90%, specificity 100%, positive predictive value 100% and a negative predictive value of 93.3%.The sensitivity of M. pneumoniae serology was 75%, specificity 73.3%, positive predictive value 25% and a negative predictive value of 96% considering PCR as a diagnostic standard,. Conclusion Our data underline the role of RSV and M. pneumoniae as the major cause of community-acquired lower respiratory tract infections in children aged <5 years. Disclosures All authors: No reported disclosures.

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Mean platelet volume as a diagnostic parameter of respiratory syncytial virus infection

Journal of Experimental and Clinical Medicine ◽

10.52142/omujecm.38.13 ◽

2021 ◽

Vol 38 (3) ◽

pp. 277-282

Author(s):

Hanife Hilal ANDAN ◽

Tugba TAS ◽

Güzide DOGAN ◽

Ayse Esra YILMAZ

Keyword(s):

Respiratory Tract ◽

Physical Examination ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Clinical Findings ◽

Lower Respiratory Tract Infections ◽

Positive Group ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections

Our aim was to investigate RSV related parameters by comparing clinical findings and physical examination with routinely ordered whole blood counts and biochemical variables in under two age children hospitalized for lower respiratory tract infections. The sample consisted of 193 children [RSV positive (n=85), RSV negative (n=108)] with lower respiratory tract infections from May 2010 to May 2013. Sociodemographic findings, chief complaints and physical examination findings were retrospectively evaluated. RSV positive and negative groups were compared using Chi-square test (% 95 Confidence Interval- %95 CI), Mann-Whitney U test (p:0,05). No significant differences were found in demographic variables and treatment decisions between two groups. In RSV positive group, higher hyponatremia (p ≤0.001) and AST values (p=0.003) were found. Decreased MPV were determined 71.8% in RSV positive group. RSV positive patients had decreased MPV values (OR:10.929, 95% CI). Higher hyponatremia and increased AST values were found to be associated with RSV infection; and decreased MPV was significantly related with RSV infection. This is the second study in literature within our knowledge that found decreased MPV values in RSV positive patients. The mechanism related with decreased MPV, hyponatremia, and increased AST values in RSV infection should be investigated further.

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Incidence of respiratory syncytial virus in hospitalized children less than 2 years of age with acute lower respiratory tract infections using multiplex real-time polymerase chain reaction in a tertiary care hospital

Asian Pacific Journal of Health Sciences ◽

10.21276/apjhs.2017.4.4.19 ◽

2017 ◽

Vol 4 (4) ◽

pp. 77-80

Author(s):

Gaganpreet Kaur Grewal ◽

Bimla Devi ◽

Pushpa Devi ◽

Karnail Singh

Keyword(s):

Respiratory Tract Infections ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Hospitalized Children ◽

Care Hospital ◽

Lower Respiratory Tract Infections ◽

Chain Reaction ◽

Polymerase Chain ◽

Syncytial Virus ◽

Tract Infections

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Therapeutic Antibodies for the Treatment of Respiratory Tract Infections—Current Overview and Perspectives

Vaccines ◽

10.3390/vaccines9020151 ◽

2021 ◽

Vol 9 (2) ◽

pp. 151

Author(s):

Alexie Mayor ◽

Adélaïde Chesnay ◽

Guillaume Desoubeaux ◽

David Ternant ◽

Nathalie Heuzé-Vourc’h ◽

...

Keyword(s):

Respiratory Tract Infections ◽

Inflammatory Diseases ◽

Treatment Strategies ◽

Candida Spp ◽

Medical Needs ◽

Life Threatening ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections ◽

Unmet Medical Needs

Respiratorytract infections (RTIs) are frequent and life-threatening diseases, accounting for several millions of deaths worldwide. RTIs implicate microorganisms, including viruses (influenza virus, coronavirus, respiratory syncytial virus (RSV)), bacteria (Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus and Bacillus anthracis) and fungi (Pneumocystis spp., Aspergillus spp. and very occasionally Candida spp.). The emergence of new pathogens, like the coronavirus SARS-CoV-2, and the substantial increase in drug resistance have highlighted the critical necessity to develop novel anti-infective molecules. In this context, antibodies (Abs) are becoming increasingly important in respiratory medicine and may fulfill the unmet medical needs of RTIs. However, development of Abs for treating infectious diseases is less advanced than for cancer and inflammatory diseases. Currently, only three Abs have been marketed for RTIs, namely, against pulmonary anthrax and RSV infection, while several clinical and preclinical studies are in progress. This article gives an overview of the advances in the use of Abs for the treatment of RTIs, based on the analysis of clinical studies in this field. It describes the Ab structure, function and pharmacokinetics, and discusses the opportunities offered by the various Ab formats, Ab engineering and co-treatment strategies. Including the most recent literature, it finally highlights the strengths, weaknesses and likely future trends of a novel anti-RTI Ab armamentarium.

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