Epitopes mapped onto SARS-CoV-2 receptor-binding motif by five distinct human neutralising antibodies

ABSTRACT

An Immune complex formation is mediated through intermolecular interactions between proteins and antigens. In the present study, in silico methods were used to locate, identify and provide valuable structural and energetic information that describes the dominant and energetically stabilising interactions found at the epitope-paratope interface of selected human antibodies, isolated from convalescent COVID-19 patients. These antibodies are directed toward the SARS-CoV-2 receptor-binding domain (RBD, i.e. residues 333–526). The analyzed immune complexes have shown strong in vitro neutralising activity against SARS-CoV-2 infection by targeting the receptor-binding motif (RBM, i.e. residues 437–508) within the viral SARS-CoV-2 spike RBD. Our data shows that residues Tyr449, Leu455, Phe456, Ala475, Phe486, Gln493, Gln498, Asn501, Gly502 and Tyr505 exhibit strong epitope capability. On another hand, the analyzed paratopes show a large repertoire of residues to recognise RBM epitopes by both the V_H and V_L chains within complementary determining regions (CDR), which would make it difficult to bind RBM to the human ACE2 cell receptor by residue interactions competition. Undoubtedly, our findings provide valuable structural and energetic information to those previously obtained through experimental crystallographic studies, and provides new insights about the binding interface that could provide a structural basis for rational epitope-based vaccinology.

KEYWORDS:

• Spike protein
• pandemic
• COVID 19
• epitope-paratope interactions
• monoclonal antibodies

Acknowledgments

In memory of Prof. Dr. Esteban Adrián Jáuregui (1929-2022) and Prof. PhD. Imre Gyula Csizmadia (1932-2022), were great inspirations for the authors as well as for several generations of students and scientists in our University.

CRediT authorship contribution statement

Contributions are defined using CRediT for standardised contribution descriptions. L.J.G., R.D.T., and M.N.C.Z.: methodology, data curation, visualisation. R.D.E.: resources, writing-review & editing. H.A.B. (leader): methodology, conceptualisation, formal analysis, funding acquisition, investigation, project administration, supervision, writing-original draft, writing-review & editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Grants from Universidad Nacional de San Luis (UNSL-Argentina) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-Argentina) PIP 090CO, partially supported this work.