Dromedary camels as a natural source of neutralizing nanobodies against SARS-CoV-2
Lotfi Chouchane, … , Murugan Subramanian, Jingxuan Shan
Lotfi Chouchane, … , Murugan Subramanian, Jingxuan Shan
Published February 2, 2021
Citation Information: JCI Insight. 2021;6(5):e145785. https://doi.org/10.1172/jci.insight.145785.
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Research Article COVID-19

Dromedary camels as a natural source of neutralizing nanobodies against SARS-CoV-2

Abstract

The development of prophylactic and therapeutic agents for coronavirus disease 2019 (COVID-19) is a current global health priority. Here, we investigated the presence of cross-neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dromedary camels that were Middle East respiratory syndrome coronavirus (MERS-CoV) seropositive but MERS-CoV free. The tested 229 dromedaries had anti–MERS-CoV camel antibodies with variable cross-reactivity patterns against SARS-CoV-2 proteins, including the S trimer and M, N, and E proteins. Using SARS-CoV-2 competitive immunofluorescence immunoassays and pseudovirus neutralization assays, we found medium-to-high titers of cross-neutralizing antibodies against SARS-CoV-2 in these animals. Through linear B cell epitope mapping using phage immunoprecipitation sequencing and a SARS-CoV-2 peptide/proteome microarray, we identified a large repertoire of Betacoronavirus cross-reactive antibody specificities in these dromedaries and demonstrated that the SARS-CoV-2–specific VHH antibody repertoire is qualitatively diverse. This analysis revealed not only several SARS-CoV-2 epitopes that are highly immunogenic in humans, including a neutralizing epitope, but also epitopes exclusively targeted by camel antibodies. The identified SARS-CoV-2 cross-neutralizing camel antibodies are not proposed as a potential treatment for COVID-19. Rather, their presence in nonimmunized camels supports the development of SARS-CoV-2 hyperimmune camels, which could be a prominent source of therapeutic agents for the prevention and treatment of COVID-19.

Authors

Lotfi Chouchane, Jean-Charles Grivel, Elmoubasher Abu Baker Abd Farag, Igor Pavlovski, Selma Maacha, Abbirami Sathappan, Hamad Eid Al-Romaihi, Sirin W.J. Abuaqel, Manar Mahmoud Ahmad Ata, Aouatef Ismail Chouchane, Sami Remadi, Najeeb Halabi, Arash Rafii, Mohammed H. Al-Thani, Nico Marr, Murugan Subramanian, Jingxuan Shan

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Figure 1

Transmission, structural, and functional homologies of 3 Betacoronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2).

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Transmission, structural, and functional homologies of 3 Betacoronavirus...
(A) Emergence of coronaviruses pathogenic for humans from ancestral bat viruses. (B) Schematic representation of the genome organization and functional domains of spike glycoprotein and nucleoprotein proteins for SARS-CoV, MERS-CoV, and SARS-CoV-2. The single-stranded RNA genomes of SARS-CoV, MERS-CoV, and SARS-CoV-2 include 2 large genes, the ORF1a and ORF1b genes, which encode 16 nonstructural proteins (nsp1–nsp16) that are highly conserved throughout coronaviruses. The structural genes encode the structural proteins, spike (S), envelope (E), membrane (M), and nucleocapsid (N), which are common features to all coronaviruses. Other accessory genes are unique to different coronaviruses in terms of number, genomic organization, sequence, and function. The structure of each S and N protein is shown beneath the genome organization. The S protein mainly contains the S1 and S2 subunits. The residue numbers in each region represent their positions in the S or N protein, respectively. CP, cytoplasm domain; IDR, intrinsically disordered region; FP, fusion peptide; HR, heptad repeat; NTD, N-terminal domain; RBD, receptor-binding domain; RBM, receptor-binding motif; SP, signal peptide; SR-rich, serine and arginine rich; TM, transmembrane domain. (C) The linear epitope B prediction of spike glycoprotein (S) NTD and RBD and nucleoprotein protein (N) of SARS-CoV, MERS-CoV, and SARS-CoV-2. The peak highlighted in yellow represents the predicted linear epitope by BLEP 2.0 software. The motifs of RBD and N are highly similar among the 3 viruses.