Novel anti-RSV dianionic dendrimer-like compounds: Design, synthesis and biological evaluation

Human Respiratory Syncytial Virus (RSV) is considered to be the leading cau se of lower respiratory tract disease in infants and young children. RSV is also a common pathogen in immunocompromised adults and in the elderly. RSV infection can be epidemic and is evident worldwide. Ribavirin, a small mol ecule agent, and Synagis(TM), a monoclonal neutralizing antibody, are the o nly approved drugs for treatment and prevention of RSV in high-risk patient s. This review is focused on a group of novel and specific inhibitors disco vered at Wyeth-Ayerst Research. Some of these inhibitors have IC50 < 50 nM and are active against all the tested group A and B viruses. They also have shown good efficacy in cotton rats and primates. Mechanism of action studi es indicate that the compounds inhibit the next step in infection after ads orption suggesting that fusion is the target. A strong relationship between the inhibitor structures and their anti-RSV activity was established. This relationship appears to derive from a multivalent interaction between the functional groupings of the inhibitors and the F protein, which seem to be highly complementary and directional.