Viral diseases constitute a significant global health burden. While vaccines have been developed to protect against some viral infections, there remain several different challenges with many vaccination strategies including incomplete protection, short protective responses, the continual evolution of new, resistant viral variants, and population buy-in. In addition, some individuals are unable to take vaccines due to other health issues. For these reasons, additional approaches to the control and limit the spread of viral infections is necessary. One approach is to use prophylactic viral inhibitors based on carbohydrates. Many viruses have evolved to bind to carbohydrate polymers presented on the surface of cells. These so called glycans are used by the virus to adhere to target cells, thus playing a supporting role viral entry and infection. Molecules that mimic these glycans have the potential to compete with cellular binding thus blocking viral engagement and entry. Here, we present the synthesis of a series of sulfated synthetic glycomimetics and the evaluation of their role in inhibiting viral engagement and infection. First results using a Human Papilloma Virus (HPV16) demonstrate that two different classes of compounds, long chain sulfated glycopolymers and short chain sulfated glycooligomers, can prevent viral infection, albeit through different mechanisms and with different antiviral efficiencies. Further extension of this work revealed a broad range of antiviral effects against several different viruses including Herpes Simplex Virus (HSV), Influenza A Virus (IAV), and Merkel Cell Polyomavirus (MCPyV). Current research is focused on the investigation of the broad-spectrum antiviral effects of these compounds, as well as their application to other important viruses.

Sulfated synthetic glycomimetics as broad-spectrum antivirals

ACS Spring Meeting 2021

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