Abstract Infection with the rabies virus (RABV) results, once symptoms develop, in a 100% lethal neurological disease. Post-exposure prophylaxis (PEP), consists of a combination of vaccination and anti-rabies immunoglobulins (RIGs); it is 100% effective if administered early after infection. Because of the limited availability, alternatives for RIGs are needed. To that end we evaluated a panel of 33 different lectins for their effect on RABV infection in cell culture. Several lectins, with either mannose or GlcNAc specificity elicited anti-RABV activity of which the GlcNAc specific Urtica dioica Agglutinin (UDA) was selected for further studies. UDA was found to prevent entry of the virus into the host cell. To further assess the potential of UDA, a physiologically relevant RABV infection muscle explant model was developed. Strips of dissected swine skeletal muscle that were kept in culture medium could be productively infected with the RABV. When the infection of the muscle strips was carried out in the presence of UDA, RABV replication was completely prevented. We thus developed a physiologically relevant RABV muscle infection model. UDA (i) may serve as a reference for further studies and (ii) holds promise as a cheap and simple to produce alternative for RIGs in PEP.
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