Human milk inhibits some enveloped virus infections, including SARS-CoV-2, in an intestinal model

Aknouch, Ikrame; Sridhar, Adithya; Freeze, Eline; Giugliano, Francesca Paola; van Keulen, Britt J.; Romijn, Michelle; Calitz, Carlemi; García-Rodríguez, Inés; Mulder, Lance; Wildenberg, Manon E.; Muncan, Vanesa; van Gils, Marit J.; van Goudoever, Johannes B.; Stittelaar, Koert J.; Wolthers, Katja C.; Pajkrt, Dasja


Human milk is important for antimicrobial defense in infants and has well demonstrated antiviral activity. We evaluated the protective ability of human milk against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a human fetal intestinal cell culture model. We found that, in this model, human milk blocks SARS-CoV-2 replication, irrespective of the presence of SARS-CoV-2 spike-specific antibodies. Complete inhibition of both enveloped Middle East respiratory syndrome coronavirus and human respiratory syncytial virus infections was also observed, whereas no inhibition of non-enveloped enterovirus A71 infection was seen. Transcriptome analysis after 24 h of the intestinal monolayers treated with human milk showed large transcriptomic changes from human milk treatment, and subsequent analysis suggested that ATP1A1 down-regulation by milk might be of importance. Inhibition of ATP1A1 blocked SARS-CoV-2 infection in our intestinal model, whereas no effect on EV-A71 infection was seen. Our data indicate that human milk has potent antiviral activity against particular (enveloped) viruses by potentially blocking the ATP1A1-mediated endocytic process.