Background: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory-
tract infections (ALRI) in young children, elderly and high-risk adults and results in considerable
hospitalizations. The fusions of RSV were proved to be a potent target in combating virus.
Methods: A series of newly reported isoindol-5-ones derivatives as RSV fusion inhibitors was studied
via in silico methodologies 3D-QSAR (CoMFA and CoMSIA) to explore compounds with better
activity. Internal and external cross-validation techniques were investigated.
Results: Satisfactory CoMFA model (q2=0.542, r2=0.908) and CoMSIA model (q2=0.563,
r2=0.874) were obtained. The external validation indicated that CoMFA and CoMSIA models possessed
high predictive powers with Q2
F2 values of 0.734 and 0.701, respectively. The contour maps
shows the bulky, and hydrogen bond acceptor groups at R2 position are essential to improve the
antivirus activity. The minor and hydrophobic groups such as ether bond at para-position or metaposition
of substituent group R1 may increase their activities.
Conclusion: The plots of CoMFA and CoMISA provided information of the structure–activity relationship
and revealed the chemical features affecting the antivirus activity. These results expand our
understanding of RSV fusion inhibitors and could be helpful in rationally designing of new analogs
with more potent inhibitory activities.