BackgroundHuman respiratory syncytial virus (hRSV) is a leading cause of severe lower respiratory infection and a major public health threat worldwide. To date, no vaccine or effective therapeutic agent has been developed. In a screen for potential therapeutic agents against hRSV, we discovered that an extract of Rosmarinus officinalis exerted a strong inhibitory effect against hRSV infection. Subsequent studies identified carnosic acid as a bioactive constituent responsible for anti-hRSV activity. Carnosic acid has been shown to exhibit potent antioxidant and anti-cancer activities. Anti-RSV activity of carnosic acid was further investigated in this study.MethodsEffects of extracts from various plants and subfractions from R. officinalis on hRSV replication were determined by microneutralization assay and plaque assay. Several constituents were isolated from ethyl acetate fraction of R. officinalis and their anti-RSV activities were assessed by plaque assay as well as reverse-transcription quantitative PCR to determine the synthesis of viral RNAs.ResultsAmong the tested bioactive constituents of R. officinalis, carnosic acid displayed the most potent anti-hRSV activity and was effective against both A- and B-type viruses. Carnosic acid efficiently suppressed the replication of hRSV in a concentration-dependent manner. Carnosic acid effectively suppressed viral gene expression without inducing type-I interferon production or affecting cell viability, suggesting that it may directly affect viral factors. A time course analysis showed that addition of carnosic acid 8 hours after infection still effectively blocked the expression of hRSV genes, further suggesting that carnosic acid directly inhibited the replication of hRSV.ConclusionsThe current study demonstrates that carnosic acid, a natural compound that has already been shown to be safe for human consumption, has anti-viral activity against hRSV, efficiently blocking the replication of this virus. Carnosic acid inhibited both A- and B- type hRSV, while it did not affect the replication of influenza A virus, suggesting that its antiviral activity is hRSV-specific. Collectively, this study suggests the need for further evaluation of carnosic acid as a potential treatment for hRSV.

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Human Respiratory Syncytial virus (hRSV) is a leading cause of severe lower respiratory tract diseases in the pediatric population.hRSV frequently causes severe morbidity and mortality in high risk groups including infants with congenital heart disease and the immunosuppressed patients. Although hRSV is recognized as a major public health threat and economic burden worldwide, there is no licensed vaccine and effective therapeutic agent. Viral nonstructural (NS) proteins have been known to play multiple functions for efficient viral replication and pathogenesis. Especially, diverse functions of influenza A virus NS1 have been extensively studies. Recent studies demonstrated that NS1 and NS2 of RSV also exert diverse functions to modulate cellular environment and antiviral immune responses. Since NS proteins of RSV are required for efficient replication and pathogenesis, NS mutant viruses have been tested as live-attenuated vaccines. This review will outline the recent progress in understanding the various functions of RSV NS1 and NS2.