Origin of the inhibitory activity of 4-O-substituted sialic derivatives of human parainfluenza virus

Human parainfluenza virus (hPIV) is a serious human pathogen causing upper and lower respiratory tract disease, yet there are no effective vaccines or therapies to control parainfluenza virus infections. Recently, we found that 4-O-substituted sialic derivatives have potent inhibitory activity against hPIV-1, whereas the anti-influenza inhibitor Zanamivir was less inhibitory. To elucidate the origin of the high potency inhibitory activities of these 4-O-substituted derivatives, we performed correlated fragment molecular orbital (FMO)-interfragment interaction energy (IFIE) analysis for hemagglutinin-neuraminidase (HN) glycoprotein complexes of hPIV with the derivatives and compared them with those for Zanamivir. We found key interactions between the inhibitors and the hPIV HN glycoprotein and identified important factors for the inhibitory activity. These theoretical results will be useful for the development of novel anti-hPIV drugs.