ABSTRACT
COVID-19 pandemic is not yet under control by vaccination, and effective antivirals are critical for preparedness. Here we report that macrophages and dendritic cells, key antigen presenting myeloid cells (APCs), are largely resistant to SARS-CoV-2 infection. APCs effectively captured viruses within cellular compartments that lead to antigen degradation. Macrophages sense SARS-CoV-2 and released higher levels of cytokines, including those related to cytokine storm in severe COVID-19. The sialic acid-binding Ig-like lectin 1 (Siglec-1/CD169) present on APCs, which interacts with sialylated gangliosides on membranes of retroviruses or filoviruses, also binds SARS-CoV-2 via GM1. Blockage of Siglec-1 receptors by monoclonal antibodies reduces SARS-CoV-2 uptake and transfer to susceptible target cells. APCs expressing Siglec-1 and carrying SARS-CoV-2 are found in pulmonary tissues of non-human primates. Single cell analysis reveals the in vivo induction of cytokines in those macrophages. Targeting Siglec-1 could offer cross-protection against SARS-CoV-2 and other enveloped viruses that exploit APCs for viral dissemination, including those yet to come in future outbreaks.
Competing Interest Statement
A patent application related to this work has been filed (US 63/152,346). Unrelated to the submitted work, J.C., J.B., and B.C. are founders and shareholders of AlbaJuna Therapeutics, S.L; B.C. is founder and shareholder of AELIX Therapeutics, S.L; H.H. is co-founder and shareholder of OmniScope Limited; J.M-P. reports institutional grants and educational/consultancy fees from AbiVax, Astra-Zeneca, Gilead Sciences, Grifols, Janssen, Merck and ViiV Healthcare; and N.I-U. reports institutional grants from Pharma Mar and Dentaid. The authors declare that no other competing financial interests exist.
Footnotes
↵+ senior authorships