ABSTRACT
In the genomes of different organisms, there are periodicities, i.e. fragments of DNA (RNA)-sequences formed by tandem repetition of the basic monomer (period). The spectra of periodicities with lengths exceeding the 'noise' threshold are quite compact and visible even for complete genomes. This makes them an acceptable tool for differentiating closely related objects. The objects of analysis in this work are the periodicities at genomes of three species of coronavirus: MERS, SARS, and SARS-CoV-2. It has been shown that there are markers in the form of periodicities that make it possible to distinguish between these species of coronaviruses. None of the periodicities identified in the genomes of the MERS species (except for the poly-a tract in the 3'UTR) is found in the genomes of SARS and SARS-CoV-2 and vice versa. Revealed periodicities common to SARS and SARS-CoV-2, as well as inherent only to genomes of one species. The number of periodicities in SARS and SARS-CoV-2 significantly exceeds the number of periodicities in random sequences. The periodicities found in almost all genomes of only 'their' species are of the greatest interest in terms of revealing the pathogenic potential of the virus. © 2021 Institute of Physics Publishing. All rights reserved.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of SARS CoV and SARS CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that among the genomes analyzed, two sequence regions in the N-terminal domain "MESEFR" and "SYLTPG" are specific to human SARS CoV-2. In the receptor-binding domain, two sequence regions "VGGNY" and "EIYQAGSTPCNGV" and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources, and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV-2 genomes. The bat SARS CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression toward becoming human SARS CoV-2.
Subject(s)
Betacoronavirus/chemistry , Host-Pathogen Interactions/physiology , Peptidyl-Dipeptidase A/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/genetics , Betacoronavirus/metabolism , Binding Sites , Chiroptera/virology , Disulfides/chemistry , Evolution, Molecular , Humans , Phylogeny , SARS-CoV-2 , Sequence Alignment , Spike Glycoprotein, Coronavirus/metabolismABSTRACT
This report describes the isolation, molecular characterization, and phylogenetic analysis of the first three complete genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from three patients involved in the first outbreak of COVID-19 in Lombardy, Italy. Early molecular epidemiological tracing suggests that SARS-CoV-2 was present in Italy weeks before the first reported cases of infection.