September 19th 2024

Published in Nature: First insights into the Porcine Deltacoronavirus spike

Published in Nature: First insights into the Porcine Deltacoronavirus spike

Further to CARE’s SARS-CoV-2 research, CARE partner Utrecht University (UU) has studied the Porcine Deltacoronavirus (PDCoV) spike, providing crucial insights for developing antiviral strategies. PDCoV, an emerging enteric pathogen in pigs, has recently been detected in children with acute febrile illness. PDCoV enters cells by binding its spike (S) protein to the host receptor aminopeptidase N (APN) and can use the APN of different species, ranging from humans, felines to chickens, highlighting its capacity for interspecies transmission. Despite this zoonotic threat, the antigenic structure of PDCoV, i.e. the molecular structures on the surface of viruses that are recognized by the immune system and are capable of triggering immune responses, remains unknown.

UU and collaborators generated and characterized a set of human monoclonal antibodies (mAbs) targeting the S protein, which can effectively neutralize virus infection. Through an integrated approach involving functional and structural analyses, UU successfully pinpointed three vulnerable regions within the prefusion S trimer. The team showed that mAb binding to the spike S1A domain is important to shift the S1B domain towards an open conformation, which is necessary for binding to the APN receptor. Other antibodies targeting the S1B domain inhibited binding to the receptor, thereby preventing infection. The epitopes of these S1B-targeting antibodies were concealed in the prefusion S trimer conformation, suggestive of an intriguing immune evasion mechanism in PDCoV. One S1B mAb, broadly reactive against avian deltacoronaviruses, targeted a highly conserved epitope on S1B that entirely overlapped with APN-interacting residues.

The identification of neutralizing epitopes on the PDCoV S protein provides essential functional and structural insights for understanding humoral immune response against this zoonotic pathogen. These discoveries hold promise for developing potent tools for outbreak preparedness against prospective deltacoronaviruses in humans.

To learn more, click here: Neutralizing Antibodies Reveal Cryptic Vulnerabilities and Interdomain Crosstalk in the Porcine Deltacoronavirus Spike