key: cord-0804725-uhru7rn8
authors: Lazar, Mihaela; Popovici, Odette; Mühlemann, Barbara; Durfee, Tim; Stan, Razvan
title: Whole-Genome Sequences of the Severe Acute Respiratory Syndrome Coronavirus-2 obtained from Romanian patients between March and June of 2020
date: 2020-07-07
journal: bioRxiv
DOI: 10.1101/2020.06.28.175802
sha: 5f13dd0edda08282f9b69aae319bb67ff68b7970
doc_id: 804725
cord_uid: uhru7rn8

Impact of mutations on the evolution of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) are needed for ongoing global efforts to track and trace the current pandemic, in order to enact effective prevention and treatment options. SARS-Co-V-2 viral genomes were detected and sequenced from 18 Romanian patients suffering from coronavirus disease-2019. Viral Spike S glycoprotein sequences were used to generate model structures and assess the role of mutations on protein stability. We integrated the phylogenetic tree within the available European SARS-Co-V-2 genomic sequences. We further provide an epidemiological overview of the pre-existing conditions that are lethal in relevant Romanian patients. Non-synonymous mutations in the viral Spike glycoprotein relating to infectivity are constructed in models of protein structures. Continuing search to limit and treat SARS-CoV-2 benefit from our contribution in delineating the viral Spike glycoprotein mutations, as well as from assessment of their role on protein stability or complex formation with human receptor angiotensin-converting enzyme 2. Our results help implement and extend worldwide genomic surveillance of coronavirus disease-2019.

difference in protein stability between Spike protein:RBD complex and Spike protein alone is 8 0 indicated. For in silico docking, the HawkDock server (http://cadd.zju.edu.cn/hawkdock/) was 8 1 used to conduct docking simulations between our modeled Spike S protein structures and ACE2.

All molecular structures were visualized with PyMol. 22.06.2020, and summarized the data in Table 1 . We compared our data to public information on 8 7 national testing relevant for this pandemic, valid at the time of writing. gender differences in the levels and activity of ACE2, as has been observed in murine models 1 0 4

[11]. showed that the Romanian sequences belonged to different clusters ( Figure 1 ). The following Table 2 . We note that only the N439K variant mutations on the stability of the complexes made with hACE2 is also indicated in Table 2 . We used PDBsum to identify the critical amino acids at the binding interface, and further compiled with PyMol their identity (Table 2) , where residues interfacing with multiple H-bonds interface, has only negligible positive effect on binding, but ranks above the rest of the variants. Mutations in the spike surface glycoprotein may be conducive to conformational changes, which 1 5 0

can translate into changing antigenicity. As such, identifying the amino acids involved in overall thermodynamic stability of the protein variants is thus imperative, as shown in Table 3 . is embedded into an immunodominant antibody epitope and is recognized by monoclonal 1 6 0 antibodies isolated from recovered individuals, who had been infected with the original SARS- indicates that the former is less stable thermodynamically, which translates into markedly Furthermore, pseudoviruses containing both of these variants were neutralized with comparable study design, analysis or writing of report. 

A pneumonia outbreak associated with a new coronavirus