Screening and Identification of Multiple Peptides Homologous to the Fusion Glycoprotein Gc of Schmallenberg Virus Able to Inhibit Viral Infection

Arthropod-borne viruses have been responsible for several emerging infections, causing a global issue in both human and veterinary fields. Within the Orthobunyaviruses, a novel and major member is the Schmallenberg virus (SBV) first detected in central Europe in 2011, and soon after was able to spread all over the continent by causing severe infection in ruminants, leading to abortion and congenital malformations. The viral particle is surrounded by a membrane in which two glycoproteins (Gn and Gc) mediate the entry, mainly through the class II fusion protein Gc, but this event requires the presence of Gn. Therefore, Gn and Gc may represent a target for antiviral development. In our study, we evaluated the inhibitory effect mediated by overlapping peptides designed on the amino acid sequences of Gc and Gn and spanning their entire length. A brute analysis of both glycoproteins was performed to explore the inhibitory effect of such peptides against SBV infection. Five out of 63 Gc peptides at a concentration of 100 μM reached 50% of inhibition and, interestingly, they are mainly distributed near the C-terminal domain. None of the 20 Gn peptides inhibited the infection, and no peptide toxicity was observed. Our findings could identify new putative domains, located at the C-terminal of Gc, in the process of SBV penetration; therefore, these results are relevant to the potential development of novel therapeutic agents for the treatment of SBV infections and could serve as a model for many human pathogens belonging to the same family.