Search

New therapies to treat or prevent viral infections are essential, as recently observed during the COVID-19 pandemic. Here, we propose a therapeutic strategy based on monoclonal antibodies that block the specific interaction between the host receptor Siglec-1/CD169 and gangliosides embedded in the viral envelope. Antibodies are an excellent option for treating infectious diseases based on their high specificity, strong targeting affinity, and relatively low toxicity. Through a process of humanization, we optimized monoclonal antibodies to eliminate sequence liabilities and performed biophysical characterization. We demonstrated that they maintain their ability to block viral entry into myeloid cells. These molecular improvements during the discovery stage are key if we are to maximize efforts to develop new therapeutic strategies. Humanized monoclonal antibodies targeting CD169 provide new opportunities in the treatment of infections caused by ganglioside-containing enveloped viruses, which pose a constant threat to human health. In contrast with current neutralizing antibodies that bind antigens on the infectious particle, our antibodies can prevent several types of enveloped viruses interacting with host cells because they target the host CD169 protein, thus becoming a potential pan-antiviral therapy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J. Martinez-Picado reports financial support from the Spanish Ministry of Science, Innovation and Universities (grants PID2022–139271OB-I00 and CB21/13/00063) and in part by Grifols. His laboratory has been funded by the NIH/NIAID (1 UM1 AI164561–01 and 1P01AI178376–01), EU HORIZON-HLTH-2021-DISEASE-04–07 (grants 101057100 and 101095606, European Union), Fundació La Marató de TV3 (grant 202130–30–31–32, Spain), and Generalitat de Valencia (grant PROMETEO/2021/036, Spain). He has also received institutional grants and educational/consultancy fees from AbiVax, AstraZeneca, Gilead Sciences, Grifols, Janssen, Merck Sharp & Dohme, and ViiV Healthcare, all outside the submitted work. P. Resa-Infante reports financial support from the Government of Catalonia Agency for Administration of University and Research Grants. N. Izquierdo-Useros reports financial support from the Spain Ministry of Science and Innovation and Universities (grant PID2020–117145RB-I00 and 10.13039/501100011033, Spain) and EU HORIZON-HLTH-2021CORONA-01 (grant 101046118, European Union). She also has received institutional funding from Pharma Mar, Grifols, HIPRA, and Amassence, all outside the submitted work. A patent application based on this work has been filed with the European Patent Office (Application form no.: EP23382072) that include P. Resa-Infante, I. Erkizia, N. Izquierdo-Useros and J. Martinez-Picado as inventors.The remaining authors declare that they have no known competing financial interests or personal relationships that could affect the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)