Filoviruses Utilize Glycosaminoglycans for Their Attachment to Target

Filoviruses are the cause of severe hemorrhagic fever in human and nonhuman primates. The envelope glycoprotein (GP), re-sponsible for both receptor binding and fusion of the virus envelope with the host cell membrane, has been demonstrated to in-teract with multiple molecules in order to enhance entry into host cells. Here we have demonstrated that filoviruses utilize gly-cosaminoglycans, andmore specifically heparan sulfate proteoglycans, for their attachment to host cells. This interaction is mediated by GP and does not require the presence of the mucin domain. Both the degree of sulfation and the structure of the carbohydrate backbone play a role in the interaction with filovirus GPs. This new step of filovirus interaction with host cells can potentially be a new target for antiviral strategies. As such, we were able to inhibit filovirus GP-mediated infection using carra-geenan, a broad-spectrummicrobicide that mimics heparin, and also using the antiviral dendrimeric peptide SB105-A10, which interacts with heparan sulfate, antagonizing the binding of the virus to cells. Filoviruses are among the most virulent pathogens that affecthumans, causing viral hemorrhagic fever (1). The family is comprised of the Marburgvirus (MARV) genus, with various strains of Lake Victoria MARV, and the Ebolavirus genus, with 5 species, Sudan ebolavirus (SUDV), Zaire ebolavirus (EBOV), Taï Forest ebolavirus (TAFV), Reston ebolavirus (RESTV), and Bundibugyo ebolavirus (BEBOV). More recently, a new genus has been proposed after the identification of the provisionally named Lloviu virus (LLOV) in dead insectivorous bats found in caves i