In-Silico evidence for two receptors based strategy of SARS-CoV-2

Abstract

We propose a novel 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 iso-electron density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, that was unfeasible with previous methods. We first tested the method with a large dataset of known protein complexes obtaining an overall area under the ROC curve of 0.76 in the blind recognition of binding sites and then applied it to investigate the features of the interaction between the Spike protein of SARS-CoV-2 and human cellular receptors. Our results indicate that SARS-CoV-2 uses a dual strategy: its spike protein could also interact with sialic acid receptors of the cells in the upper airways, in addition to the known interaction with Angiotensin-converting enzyme 2.

ACE 2 Coding Variants: A Potential X-linked Risk Factor for COVID-19 Disease

“…Our 3D modelling predicted p.Lys26Arg to lie immediately beside the ACE2-Spike protein interface (albeit with the lysine side chain pointing away from the interface). Prior work on ACE2 binding to SARS-CoV 18, 26 and recent work on ACE2 binding to SARS-CoV-2 27, 28 by others has identified three main S protein binding domains within ACE2. The largest includes Gln24, Thr27, Phe28, Asp30, Lys31, His34, Glu35, Asp38, Tyr41, Gln42 and Leu45.…”

Potential pathogenesis of ageusia and anosmia in COVID‐19 patients

“…8 Moreover, the Middle East Respiratory Syndrome (MERS) coronavirus may bind to the sialic acid receptors, 9 an ability that has also recently been described for SARS-CoV-2. 10 Sialic acid is a fundamental component of the salivary mucin, and it protects the glycoproteins that convey gustatory molecules inside the taste pores from premature enzymatic degradation. 11 A reduction of sialic acid in the saliva is associated with an increase in the gustatory threshold.…”

N-terminal domain (NTD) of SARS-CoV-2 spike-protein structurally resembles MERS-CoV NTD sialoside-binding pocket

“…2 and 3). While, the β4-β5 loop is involved in the engagement with all sialosides, the β14-β15 loop is speci c to larger sialic acids such as sLex (Figs 2 and 3) which possibly suggest to have preferential interaction with α2,3-Linked sialosides as in MERS-CoV [25,26]. The predicted interacting sites of the tested sialosides are mapped in Fig.…”

“…In addition, a single-turn alpha helix (Thr20-Leu24) formed key interactions with all sialosides tested. Interestingly, the NTD of MERS-CoV also displays a single-turn helix (Gln37-Phe40), which is important for sialoside binding [25]. However, both the SARS-CoV and HCoV-OC43 spike proteins lack this element [7,10,13,18,26].…”