Milanetti, EdoardoMiotto, MattiaDi Rienzo, LorenzoNagaraj, MadhuMonti, MicheleGolbek, Thaddeus W.Gosti, GiorgioRoeters, Steven J.Weidner, TobiasOtzen, Daniel E.Ruocco, Giancarlo2021-11-222021-11-222021Milanetti E, Miotto M, Di Rienzo L, Nagaraj M, Monti M, Golbek TW, Gosti G, Roeters SJ, Weidner T, Otzen DE, Ruocco G. In-silico evidence for a two receptor based strategy of SARS-CoV-2. Front Mol Biosci. 2021;8:690655. DOI: 10.3389/fmolb.2021.6906552296-889Xhttp://hdl.handle.net/10230/49029We 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.application/pdfeng© 2021 Milanetti, Miotto, Di Rienzo, Nagaraj, Monti, Golbek, Gosti, Roeters, Weidner, Otzen and Ruocco. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.info:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fmolb.2021.690655SARS-CoV-2Shape complementaritySialic acidSpike (S) proteinZernike momentsinfo:eu-repo/semantics/openAccess