key: cord-328122-nfvbog77
authors: Tresoldi, Ilaria; Sangiuolo, Carla F.; Manzari, Vittorio; Modesti, Andrea
title: SARS‐COV‐2 and infectivity: Possible increase in infectivity associated to integrin motif expression
date: 2020-04-10
journal: J Med Virol
DOI: 10.1002/jmv.25831
sha: 
doc_id: 328122
cord_uid: nfvbog77

SARS-COV2 represents the causal agent of a potentially fatal disease (COVID-19) that is actually of great global public health concern. SARS-COV2 has diffused throughout the world surprisingly fast demonstrating a far greater infectivity than previously known human coronaviruses and it is also responsible for an unusual high variety of symptoms in affected patients. This article is protected by copyright. All rights reserved.

To the Editor, Severe acute respiratory syndrome coronavirus 2 (SARS- represents the causal agent of a potentially fatal disease (coronavirus disease 2019) that is actually of great global public health concern.

SARS-COV-2 has diffused throughout the world surprisingly fast demonstrating a far greater infectivity than previously known human coronaviruses and it is also responsible for an unusual high variety of symptoms in affected patients.

Since viruses need to penetrate cells to replicate, one of their most important characteristics is the ability to interact with the cell membrane.

Different viruses utilize different approaches to penetrate into the cell, but they all use cell receptors through a method that mimics the receptor's ligand binding.

The virus transmission efficiency is directly correlated to the affinity of the virus to its cell membrane receptor. The presence of different receptors for the same virus on different cell types has been demonstrated, but even on the same cell, there can be different kind of receptors for the same virus.

It has been proposed that SARS-COV-2 has acquired the spike glycoprotein RGD (KGD in SARS-CoV) 1 integrin-binding site which is considered significant for the virus transmission efficiency. The sequence arginine-glycine-aspartic acid (RGD) was identified as a general integrin-binding motif, but individual integrins are also specific for particular protein ligands.

The most common of these motifs is the minimal peptide sequence for binding integrins, RGD, which is known for its role in virus infection via its ability to interact with over half of the more than 20 known integrins. 2 A few integrins are more restricted than others to certain cell lineages, but the expression is often developmentally regulated. Integrins were also found to be overexpressed on the surface of several inflamed tissues. 4 Besides the fibronectin binding motif RGD, other integrinbinding sites are specifically expressed in SARS-COV-2, and, particularly, a change from a LDV to a LDI motif is likely significant. The LDV/LDI switch in human immunodeficiency virus infection has been shown to play a key role in strain diffusion, contributing to high viral infectivity. 5 We investigated the protein sequence of the human coronavirus and compared it to SARS and bat coronavirus to identify any eventual overexpression of other integrin-binding sites.

As expected, many integrin-binding motifs were conserved on the three sequences, but others were differently distributed. Interestingly, binding sequences of the SARS-COV-2 seems to be more similar to bat virus than SARS-Cov virus. Orf1ab polyprotein has many integrin-binding motifs implicated in cell adhesion with binding sites on Fibronectin, Tenascin_C, and VCAM. This polyprotein has

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