Lijuan Yuan, Viginia Tech

1. Department of Chemistry, Virginia Tech, Blacksburg, VA, United States. 2. Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States.

Combatting and Exploiting dsRNA viruses

Rotaviruses are a leading cause of severe diarrhea, especially in children under five in developing countries. While several vaccines are available and new vaccines are currently being developed, the virus continues to be responsible for more than 200,000 deaths each year. Treatment strategies rely primarily on oral and intravenous rehydration. As no specific antiviral drugs are available, there is an urgent need for alternative therapeutic approaches. Sialic acid (SA), a common rotavirus receptor on host cell membranes, plays a crucial role in viral adhesion and infection. To mimic these interactions, we synthesized a library of SA-containing polymers, which can serve as decoy targets, binding to the virus surface and inhibiting infection. When conjugated to a polymer backbone, SA can engage in polyvalent interactions that enhance viral inhibition by blocking viral entry. Specifically, we synthesized SA–poly(sodium 4-styrenesulfonate) (SA-PSS) conjugates, utilizing PSS for its broad-spectrum antiviral potential. By systematically varying polymer chain length and SA content, we identified an optimal material with a degree of polymerization of 279 and SA content of 3% and 5%, which exhibited the highest antiviral efficacy. Notably, these conjugates remained effective at concentrations as low as 9.77 μg/mL in PBS, demonstrating their strong inhibitory activity against human rotavirus (Wa strain, G1P[8] on MA104 cells). This approach provides a versatile synthetic platform for the rational design of potent polymer-based antiviral therapeutics. These findings will contribute to the development of new strategies to combat rotavirus infections and offer insights into polymer-based approaches for antiviral drug design.