Exploring the Association Between Sialic Acid and SARS-CoV-2 Spike Protein Through a Molecular Dynamics-Based Approach

被引:29
作者
Bo, Leonardo [1 ]
Miotto, Mattia [1 ,2 ]
Di Rienzo, Lorenzo [1 ]
Milanetti, Edoardo [1 ,2 ]
Ruocco, Giancarlo [1 ,2 ]
机构
[1] Ist Italiano Tecnol, Ctr Life Nanosci, Rome, Italy
[2] Sapienza Univ, Dept Phys, Rome, Italy
来源
FRONTIERS IN MEDICAL TECHNOLOGY | 2021年 / 2卷
关键词
sialic acid; SARS-; CoV-2; molecular dynamics; molecular binding; entry mechanism; I-TASSER; CORONAVIRUS; RECEPTOR; IDENTIFICATION; DETERMINANTS; SYSTEMS; SARS;
D O I
10.3389/fmedt.2020.614652
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Recent experimental evidence demonstrated the capability of SARS-CoV-2 Spike protein to bind sialic acid molecules, which was a trait not present in SARS-CoV and could shed light on the molecular mechanism used by the virus for the cell invasion. This peculiar feature has been successfully predicted by in-silico studies comparing the sequence and structural characteristics that SARS-CoV-2 shares with other sialic acid-binding viruses, like MERS-CoV. Even if the region of the binding has been identified in the N-terminal domain of Spike protein, so far no comprehensive analyses have been carried out on the spike-sialic acid conformations once in the complex. Here, we addressed this aspect performing an extensive molecular dynamics simulation of a system composed of the N-terminal domain of the spike protein and a sialic acid molecule. We observed several short-lived binding events, reconnecting to the avidic nature of the binding, interestingly occurring in the surface Spike region where several insertions are present with respect to the SARS-CoV sequence. Characterizing the bound configurations via a clustering analysis on the Principal Component of the motion, we identified different possible binding conformations and discussed their dynamic and structural properties. In particular, we analyze the correlated motion between the binding residues and the binding effect on the stability of atomic fluctuation, thus proposing regions with high binding propensity with sialic acid.
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页数:10
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