Iterative Optimization and Structure-Activity Relationship Studies of Oseltamivir Amino Derivatives as Potent and Selective Neuraminidase Inhibitors Targeting 150-Cavity.

With our continuous endeavors in seeking neuraminidase (NA) inhibitors, we reported herein three series of novel oseltamivir amino derivatives with the goal of exploring the druggable chemical space inside the 150-cavity of influenza virus NAs. Among them, around half of the compounds in were demonstrated to be better inhibitors against both wild-type and oseltamivir-resistant group-1 NAs than oseltamivir carboxylate (OSC). Notably, compounds , , , and showed more potent or equipotent antiviral activity against H1N1, H5N1, and H5N8 viruses compared to OSC in cellular assays.

Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins.

Influenza is an acute respiratory infectious disease caused by the influenza virus, affecting people globally and causing significant social and economic losses. Due to the inevitable limitations of vaccines and approved drugs, there is an urgent need to discover new anti-influenza drugs with different mechanisms. The viral ribonucleoprotein complex (vRNP) plays an essential role in the life cycle of influenza viruses, representing an attractive target for drug design.

Identification of C5-NH Modified Oseltamivir Derivatives as Novel Influenza Neuraminidase Inhibitors with Highly Improved Antiviral Activities and Favorable Druggability.

Our previous efforts have proved that modifications targeting the 150-cavity of influenza neuraminidase can achieve more potent and more selective inhibitors. In this work, four subseries of C5-NH modified oseltamivir derivatives were designed and synthesized to explore every region inside the 150-cavity. Among them, compound was exceptionally potent against the whole panel of Group-1 NAs with IC values ranging from 0.

A pilot study on vitrectomy combined with scleral shortening for eyes with myopic macular retinoschisis-2y follow-up results.

Aim: To evaluate the effect of vitrectomy combined with scleral shortening for eyes with myopic macular retinoschisis.

Methods: Thirty-seven patients with myopic macular retinoschisis who underwent pars plana vitrectomy (PPV) combined with scleral shortening were reviewed. Axial length (AL), the height of macular retinoschisis, the height of retinal detachment if existed, the diameter of macular hole if existed and best corrected visual acuity (BCVA) were obtained.