Sulfated Glycomimetic α-Helical Polypeptides for Antiviral Activity.

In this work, we developed a library of sulfated glycomimetic polypeptides with a high sulfated degree (up to 99%) via a click reaction and sulfation modification, enabling control over the helicity, molecular weight, rigidity, and side-chain structure. Their potentials as the inhibitors of SARS-CoV-2 and common enterovirus were investigated, and the structure-activity relationship was explored in detail. The in vitro results revealed the crucial role of α-helical conformation and sulfated sugar since all the sulfated glycopolypeptides exhibited outperformed activity in suppressing SARS-CoV-2 infection with the inhibition efficiency up to 85%. Other structural properties, including the rigid chain structure and a moderate molecular weight, also contributed to blocking the viral entry into host cells. Among the sulfated glycopolypeptides, L