Viral load appears to drive disease manifestations in humans with RSV infection. The observed parallel viral and disease kinetics support a potential clinical benefit of RSV antivirals. This reproducible model facilitates the development of future RSV therapeutics.

BackgroundRespiratory syncytial virus (RSV) viral load and disease severity associate, and the timing of viral load and disease run in parallel. An antiviral must be broadly effective against the natural spectrum of RSV genotypes and must attain concentrations capable of inhibiting viral replication within the human respiratory tract.ObjectivesWe evaluated a novel RSV fusion inhibitor, MDT‐637, and compared it with ribavirin for therapeutic effect in vitro to identify relative therapeutic doses achievable in humans.Method MDT‐637 and ribavirin were co‐incubated with RSV in HEp‐2 cells. Quantitative PCR assessed viral concentrations; 50% inhibitory concentrations (IC 50) were compared to achievable human MDT‐637 and ribavirin peak and trough concentrations.Results and conclusionsThe IC 50 for MDT‐637 and ribavirin (against RSV‐A Long) was 1.42 and 16 973 ng/mL, respectively. The ratio of achievable peak respiratory secretion concentration to IC 50 was 6041‐fold for MDT‐637 and 25‐fold for aerosolized ribavirin. The ratio of trough concentration to IC 50 was 1481‐fold for MDT‐637 and 3.29‐fold for aerosolized ribavirin. Maximal peak and trough levels of oral or intravenous ribavirin were significantly lower than their IC 50s. We also measured MDT‐637 IC 50s in 3 lab strains and 4 clinical strains. The IC 50s ranged from 0.36 to 3.4 ng/mL. Achievable human MDT‐637 concentrations in respiratory secretions exceed the IC 50s by factors from hundreds to thousands of times greater than does ribavirin. Furthermore, MDT‐637 has broad in vitro antiviral activity on clinical strains of different RSV genotypes and clades. Together, these data imply that MDT‐637 may produce a superior clinical effect compared to ribavirin on natural RSV infections.

To estimate the ABO blood groups from saliva samples and to correlate with the secretor status. Materials and methodsA sample size of 300 individuals was selected from the outpatient department of Surendera Dental College & Research Institute, Sriganganagar, India, and from dental camps organized by the college in the near vicinity. Informed consent was obtained from selected individuals to collect their blood and saliva samples. Salivary samples were evaluated for ABO blood groups by the absorption-inhibition method. The indicator erythrocytes were prepared after blood group confirmation from serum. It was used to identify the blood group antigens in saliva to confirm the secretor status. The results were tabulated and the Pearson's chisquared test was performed for statistical analysis using SPSS 15.0 (SPSS Inc., Chicago, IL). ResultsThe present study showed that 282 subjects (94%) were Rhesus positive and 18 subjects (6%) were Rhesus negative. Two-hundred-and-fifty subjects (83.3%) were secretors of antigens in saliva. Non-secretors were 50 subjects (16.7%). We identified that 250/300 were secretors and the majority were in AB & A group. ConclusionBlood groups could not be detected from the saliva of subjects who were non-secretors. In contrast, blood types could be accurately identified from the saliva of those subjects who were secretors of antigen.

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