Co-crystallization of prefusion-stabilized RSV F with JNJ2408068, JNJ49153390, TMC353121, BTA9881, or BMS433771 have shown they all bind to similar central cavities formed by their homotrimer inner α-helices (Figure ABCD). Such bindings further stabilized the prefusion F state inhibiting the postfusion stable six-helix bundle formation and therefore subsequent viral penetration and infection. However, despite the high number of reports describing in vitro inhibitions of RSV-cell fusion (i.e., for instance by cell-cell syncytium tests), at low-nanoMolar ranges, only the GS5806 has been further explored clinically. GS5806 blocks the prefusion RSV F conformational changes and shows inhibition of infection in vitro and in animals. Nevertheless, several RSV-resistant mutations emerged during GS5806 treatment tests of RSV controlled infections in human volunteers . The need for alternative small molecular RSV inhibitor drugs including those to F resistant mutations remains.