In-Silico Evidence for a Two Receptor Based Strategy of SARS-CoV-2

Edoardo Milanetti; Mattia Miotto; Lorenzo Di Rienzo; Madhu Nagaraj; Michele Monti; Thaddeus W Golbek; Giorgio Gosti; Steven J Roeters; Tobias Weidner; Daniel E Otzen; Giancarlo Ruocco

doi:10.3389/fmolb.2021.690655

In-Silico Evidence for a Two Receptor Based Strategy of SARS-CoV-2

Front Mol Biosci. 2021 Jun 9:8:690655. doi: 10.3389/fmolb.2021.690655. eCollection 2021.

Authors

Edoardo Milanetti^{1

2}, Mattia Miotto^{1

2}, Lorenzo Di Rienzo², Madhu Nagaraj³, Michele Monti^{4

5}, Thaddeus W Golbek⁶, Giorgio Gosti², Steven J Roeters⁶, Tobias Weidner⁶, Daniel E Otzen³, Giancarlo Ruocco^{1

2}

Affiliations

¹ Department of Physics, Sapienza University, Rome, Italy.
² Center for Life Nano and Neuro Science, Italian Institute of Technology, Rome, Italy.
³ Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark.
⁴ Centre for Genomic Regulation (CRG), the Barcelona Institute for Science and Technology, Barcelona, Spain.
⁵ RNA System Biology Lab, Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa, Italy.
⁶ Department of Chemistry, Aarhus University, Aarhus, Denmark.

Abstract

We propose a computational investigation on the interaction mechanisms between SARS-CoV-2 spike protein and possible human cell receptors. In particular, we make use of our newly developed numerical method able to determine efficiently and effectively the relationship of complementarity between portions of protein surfaces. This innovative and general procedure, based on the representation of the molecular isoelectronic density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, which was unfeasible with previous methods. Our results indicate that SARS-CoV-2 uses a dual strategy: in addition to the known interaction with angiotensin-converting enzyme 2, the viral spike protein can also interact with sialic-acid receptors of the cells in the upper airways.

Keywords: SARS-CoV-2; shape complementarity; sialic acid; spike (S) protein; zernike moments.