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Article: Change of Antigenic Determinants of SARS-CoV-2 Virus S-Protein as a Possible Cause of Antibody-Dependent Enhancement of Virus Infection and Cytokine Storm.

Nechipurenko, Yu D / Anashkina, A A / Matveeva, O V

2020 Volume 65, Issue 4, Page(s) 703–709

Abstract: A hypothesis is proposed that the cytokine storm syndrome, which complicates COVID-19 in some patients, is a consequence of antibody-dependent enhancement of virus infection, which is in turn happens due to a change in dominant antigenic determinants of ... ...

Abstract	A hypothesis is proposed that the cytokine storm syndrome, which complicates COVID-19 in some patients, is a consequence of antibody-dependent enhancement of virus infection, which is in turn happens due to a change in dominant antigenic determinants of SARS-CoV-2 S-protein. The antibody-dependent enhancement of virus infection is a phenomenon in which virus-specific antibodies that are not neutralizing enhance the entry of infectious virus into immune cells causing their death. Antibody-dependent enhancement has been reported for different coronaviruses. This phenomenon happens due to a decrease in the binding strength of neutralizing antibodies to the virus, which converts these antibodies into suboptimal-not neutralizing ones. According to our hypothesis, such a decrease in affinity may be associated with a change in the conformation of the viral S-protein. We believe that this conformational change is the major factor in the switching of antibodies affinity, which triggers antibody-dependent enhancement. However, other factors that contribute to antigen drift and antigenic determinant changes may also play a role.
Keywords	covid19
Language	English
Publishing date	2020-10-19
Publishing country	England
Document type	Journal Article
ZDB-ID	6617-5
ISSN	1555-6654 ; 0006-3509
ISSN (online)	1555-6654
ISSN	0006-3509
DOI	10.1134/S0006350920040119
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Article: Change of Antigenic Determinants of SARS-CoV-2 Virus S-Protein as a Possible Cause of Antibody-Dependent Enhancement of Virus Infection and Cytokine Storm

Nechipurenko, Yu D. / Anashkina, A. A. / Matveeva, O. V.

Biofizika

Abstract: A hypothesis is proposed that the cytokine storm syndrome, which complicates the process of severe COVID-19 patients, is a consequence of antibody-dependent enhancement of viral infection, which in turn according to our hypothesis happens due to a ... ...

Abstract	A hypothesis is proposed that the cytokine storm syndrome, which complicates the process of severe COVID-19 patients, is a consequence of antibody-dependent enhancement of viral infection, which in turn according to our hypothesis happens due to a variation in dominant antigenic determinants of the SARS-CoV-2 S protein The antibody-dependent enhancement of viral infection is a phenomenon in which virus-specific antibodies which are not neutralizing enhance viral entry into immune complexes through the binding to receptors resulting in the death of the host cells Antibody-dependent enhancement has been reported to be exploited by a variety of coronaviruses In these cases, enhancement of viral infection can be triggered by variation in antigenic determinants of the S protein This variation, according to our hypothesis, may lead to weaker binding of neutralizing antibodies to the virus, affecting the efficiency of these antibodies in protection against the virus - instead of neutralization viral suppression appears to be suboptimal Variation in antigenic determinants (linear epitopes and conformational epitopes) may occur due to variation in S protein amino-acid composition Variation in S protein amino acid composition is a consequence of the genetic diversity of quasi-species We hypothesize that this variation may cause not only structural changes in the S protein, but also affect the dynamics of changes in its conformations All these events can be observed in individuals infected with SARS-CoV-2 thereby explaining a severe course of the disease Предложена гипотеза о том, что цитокиновый шторм, возникающий как осложнение у больных COVID-19, является следствием феномена антителозависимого усиления инфекции, а сам феномен в свою очередь обусловлен изменением доминантных антигенных детерминант в шиповидном S-белке вируса SARS-CoV-2 Антителозависимое усиление инфекции - это явление, при котором связывание вируса с субоптимальными антителами, которые не являются нейтрализующими, индуцирует проникновение вируса в клетки иммунной системы, что приводит к их массовой гибели Явление антителозависимого усиления инфекции показано для ряда коронавирусов Усиление инфекции в этих случаях может быть спровоцировано изменением антигенных детерминант S-белка Такое изменение может приводить, согласно нашей гипотезе, к уменьшению прочности связывания нейтрализующих антител с вирусом, превращая их в субоптимальные - не нейтрализующие Изменчивость линейных и/или конформационных антигенных детерминант S-белка может реализоваться за счет вариабельности ряда аминокислот в этом белке Эта вариабельность является следствием генетического разнообразия квазивидов Подобная изменчивость может вызывать не только структурные изменения в S-белке, но и влиять на динамику смены его конформаций Все эти явления могут происходить в процессе вирусной инфекции SARS-CoV-2 и объяснять тяжелое течении болезни у некоторых зараженных
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #859390
Database	COVID19

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Article ; Online: Structural features of DNA that determine RNA polymerase II core promoter.

Il'icheva, Irina A / Khodikov, Mingian V / Poptsova, Maria S / Nechipurenko, Dmitry Yu / Nechipurenko, Yury D / Grokhovsky, Sergei L

BMC genomics

2016 Volume 17, Issue 1, Page(s) 973

Abstract: Background: The general structure and action of all eukaryotic and archaeal RNA polymerases machinery have an astonishing similarity despite the diversity of core promoter sequences in different species. The goal of our work is to find common ... ...

Abstract	Background: The general structure and action of all eukaryotic and archaeal RNA polymerases machinery have an astonishing similarity despite the diversity of core promoter sequences in different species. The goal of our work is to find common characteristics of DNA region that define it as a promoter for the RNA polymerase II (Pol II). Results: The profiles of a large number of physical and structural characteristics, averaged over representative sets of the Pol II minimal core promoters of the evolutionary divergent species from animals, plants and unicellular fungi were analysed. In addition to the characteristics defined at the base-pair steps, we, for the first time, use profiles of the ultrasonic cleavage and DNase I cleavage indexes, informative for internal properties of each complementary strand. Conclusions: DNA of the core promoters of metazoans and Schizosaccharomyces pombe has similar structural organization. Its mechanical and 3D structural characteristics have singular properties at the positions of TATA-box. The minor groove is broadened and conformational motion is decreased in that region. Special characteristics of conformational behavior are revealed in metazoans at the region, which connects the end of TATA-box and the transcription start site (TSS). The intensities of conformational motions in the complementary strands are periodically changed in opposite phases. They are noticeable, best of all, in mammals. Such conformational features are lacking in the core promoters of S. pombe. The profiles of Saccharomyces cerevisiae core promoters significantly differ: their singular region is shifted down thus pointing to the uniqueness of their structural organization. Obtained results may be useful in genetic engineering for artificial modulation of the promoter strength.
MeSH term(s)	Animals ; Base Sequence ; DNA Cleavage ; Genetic Variation ; Humans ; Nucleotide Motifs ; Promoter Regions, Genetic ; RNA Polymerase II/chemistry ; RNA Polymerase II/genetics ; Schizosaccharomyces/genetics ; TATA Box ; Transcription Initiation Site
Chemical Substances	RNA Polymerase II (EC 2.7.7.-)
Language	English
Publishing date	2016--25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2164
ISSN (online)	1471-2164
DOI	10.1186/s12864-016-3292-z
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Article ; Online: Non-random DNA fragmentation in next-generation sequencing.

Poptsova, Maria S / Il'icheva, Irina A / Nechipurenko, Dmitry Yu / Panchenko, Larisa A / Khodikov, Mingian V / Oparina, Nina Y / Polozov, Robert V / Nechipurenko, Yury D / Grokhovsky, Sergei L

Scientific reports

2014 Volume 4, Page(s) 4532

Abstract: Next Generation Sequencing (NGS) technology is based on cutting DNA into small fragments, and their massive parallel sequencing. The multiple overlapping segments termed "reads" are assembled into a contiguous sequence. To reduce sequencing errors, every ...

Abstract	Next Generation Sequencing (NGS) technology is based on cutting DNA into small fragments, and their massive parallel sequencing. The multiple overlapping segments termed "reads" are assembled into a contiguous sequence. To reduce sequencing errors, every genome region should be sequenced several dozen times. This sequencing approach is based on the assumption that genomic DNA breaks are random and sequence-independent. However, previously we showed that for the sonicated restriction DNA fragments the rates of double-stranded breaks depend on the nucleotide sequence. In this work we analyzed genomic reads from NGS data and discovered that fragmentation methods based on the action of the hydrodynamic forces on DNA, produce similar bias. Consideration of this non-random DNA fragmentation may allow one to unravel what factors and to what extent influence the non-uniform coverage of various genomic regions.
Language	English
Publishing date	2014-03-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep04532
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Article ; Online: Sequence-specific ultrasonic cleavage of DNA.

Grokhovsky, Sergei L / Il'icheva, Irina A / Nechipurenko, Dmitry Yu / Golovkin, Michail V / Panchenko, Larisa A / Polozov, Robert V / Nechipurenko, Yury D

Biophysical journal

2010 Volume 100, Issue 1, Page(s) 117–125

Abstract: ... rates) in phosphodiester bonds following deoxycytidine, which diminished in the row of dinucleotides: d ... CpG) > d(CpA) > d(CpT) >> d(CpC). The cleavage rates for all pairs of complementary dinucleotides were ...

Abstract	We investigated the phenomenon of ultrasonic cleavage of DNA by analyzing a large set of cleavage patterns of DNA restriction fragments using polyacrylamide gel electrophoresis. The cleavage intensity of individual phosphodiester bonds was found to depend on the nucleotide sequence and the position of the bond with respect to the ends of the fragment. The relative intensities of cleavage of the central phosphodiester bond in 16 dinucleotides and 256 tetranucleotides were determined by multivariate statistical analysis. We observed a remarkable enhancement of the mean values of the relative intensities of cleavage (cleavage rates) in phosphodiester bonds following deoxycytidine, which diminished in the row of dinucleotides: d(CpG) > d(CpA) > d(CpT) >> d(CpC). The cleavage rates for all pairs of complementary dinucleotides were significantly different from each other. The effect of flanking nucleotides in tetranucleotides on cleavage rates of all 16 types of central dinucleotides was also statistically significant. The sequence-dependent ultrasonic cleavage rates of dinucleotides are consistent with reported data on the intensity of the conformational motion of their 5'-deoxyribose. As a measure of local conformational dynamics, cleavage rates may be useful for characterizing functional regions of the genome.
MeSH term(s)	Base Sequence ; DNA/chemistry ; DNA/genetics ; DNA/metabolism ; Electrophoresis, Polyacrylamide Gel ; Physical Phenomena ; Pliability ; Solutions ; Ultrasonics/methods
Chemical Substances	Solutions ; DNA (9007-49-2)
Language	English
Publishing date	2010-12-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2010.10.052
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Article ; Online: Ultrasonic cleavage of nicked DNA.

Il'icheva, I A / Nechipurenko, D Yu / Grokhovsky, S L

Journal of biomolecular structure & dynamics

2009 Volume 27, Issue 3, Page(s) 391–398

Abstract: Structural properties of nicked dsDNA have been an object of numerous studies due to their special role in reparation processes. Here we report experimental results covering ultrasound irradiation of a nicked dsDNA fragments. We have quantitatively ... ...

Abstract	Structural properties of nicked dsDNA have been an object of numerous studies due to their special role in reparation processes. Here we report experimental results covering ultrasound irradiation of a nicked dsDNA fragments. We have quantitatively estimated ultrasonic cleavage rates in these fragments using the polyacrylamide gel electrophoresis. Data reveal cleavage enhancement in the regions of about 10 b. p. up and down the nick. The intensity of ultrasonic cleavage near the nick is one order of magnitude higher than intensity of ultrasonic cleavage in the same sites of the intact dsDNA fragments. At the same time, the cleavage rates in positions beyond the regions around the nick markedly grow weak comparing to the sequence-specific cleavage rates of intact dsDNA. Thus, the presence of the nick serves as an expressive structural alteration which exceeds any modulation of the structure caused by the base-pair sequence.
MeSH term(s)	Base Sequence ; DNA Breaks, Single-Stranded ; DNA Cleavage ; Molecular Sequence Data ; Nucleic Acid Conformation
Language	English
Publishing date	2009-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	49157-3
ISSN	1538-0254 ; 0739-1102
ISSN (online)	1538-0254
ISSN	0739-1102
DOI	10.1080/07391102.2009.10507325
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Article: Quantitative methods of analysis of footprinting diagrams for the complexes formed by a ligand and a DNA fragment of known sequence.

Ryabokon, V F / Nechipurenko, Yu D / Gurskii, G V

Doklady. Biochemistry and biophysics

2004 Volume 398, Page(s) 329–333

MeSH term(s)	Algorithms ; Binding Sites ; DNA Footprinting/methods ; DNA-Binding Proteins/chemistry ; Models, Chemical ; Models, Genetic ; Models, Statistical ; Netropsin/chemistry ; Protein Binding ; Reproducibility of Results ; Sensitivity and Specificity ; Sequence Analysis, DNA/methods
Chemical Substances	DNA-Binding Proteins ; Netropsin (64B3O0RD7N)
Language	English
Publishing date	2004-11-19
Publishing country	Russia (Federation)
Document type	Comparative Study ; Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't ; Validation Studies
ZDB-ID	2062390-2
ISSN	1608-3091 ; 1607-6729
ISSN (online)	1608-3091
ISSN	1607-6729
DOI	10.1023/b:dobi.0000046651.58833.95
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Article: Contextual DNA features significant for the DNA damage by the 193-nm ultraviolet laser beam.

Vtyurina, N N / Grohovsky, S L / Vasiliev, A B / Titov, I I / Ponomarenko, P M / Ponomarenko, M P / Peltek, S E / Nechipurenko, Yu D / Kolchanov, N A

Doklady. Biochemistry and biophysics

2013 Volume 447, Page(s) 267–272

MeSH term(s)	DNA Damage/physiology ; DNA, Bacterial/genetics ; DNA, Bacterial/radiation effects ; Lasers ; Radiation Dosage
Chemical Substances	DNA, Bacterial
Language	English
Publishing date	2013-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2062390-2
ISSN	1608-3091 ; 1607-6729
ISSN (online)	1608-3091
ISSN	1607-6729
DOI	10.1134/S1607672912060038
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Article: Sequence-Specific Ultrasonic Cleavage of DNA

Grokhovsky, Sergei L / Il'icheva, Irina A / Nechipurenko, Dmitry Yu / Golovkin, Michail V / Panchenko, Larisa A / Polozov, Robert V / Nechipurenko, Yury D

Biophysical journal. 2011 Jan. 5, v. 100, no. 1

2011

Abstract	We investigated the phenomenon of ultrasonic cleavage of DNA by analyzing a large set of cleavage patterns of DNA restriction fragments using polyacrylamide gel electrophoresis. The cleavage intensity of individual phosphodiester bonds was found to depend on the nucleotide sequence and the position of the bond with respect to the ends of the fragment. The relative intensities of cleavage of the central phosphodiester bond in 16 dinucleotides and 256 tetranucleotides were determined by multivariate statistical analysis. We observed a remarkable enhancement of the mean values of the relative intensities of cleavage (cleavage rates) in phosphodiester bonds following deoxycytidine, which diminished in the row of dinucleotides: d(CpG) > d(CpA) > d(CpT) >> d(CpC). The cleavage rates for all pairs of complementary dinucleotides were significantly different from each other. The effect of flanking nucleotides in tetranucleotides on cleavage rates of all 16 types of central dinucleotides was also statistically significant. The sequence-dependent ultrasonic cleavage rates of dinucleotides are consistent with reported data on the intensity of the conformational motion of their 5′-deoxyribose. As a measure of local conformational dynamics, cleavage rates may be useful for characterizing functional regions of the genome.
Keywords	DNA ; genome ; multivariate analysis ; nucleotide sequences ; nucleotides ; polyacrylamide gel electrophoresis
Language	English
Dates of publication	2011-0105
Size	p. 117-125.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2010.10.052
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The use of the thrombodynamics test in the diagnostics of hemostasis disorders in patients with COVID-19 of varying severity

Liubov V. Krechetova / Dmitry Yu. Nechipurenko / Margarita A. Shpilyuk / Olga S. Beznoshchenko / Evgeniya A. Beresneva / Mikhail I. Markelov / Tatiana Yu. Ivanets / Tatiana Yu. Gavrilova / Irena F. Kozachenko / Rosa M. Esayan / Aleksei V. Pyregov / Nelly A. Khachatryan / Dmitrii S. Kodatskii / Ilya S. Spiridonov / Nataliya V. Dolgushina / Elena A. Gorodnova / Fazoil I. Ataullakhanov / Alexander G. Rumyantsev / Dmitriy N. Degtyarev

Клиническая практика, Vol 12, Iss 4, Pp 23-

2021 Volume 37

Abstract: ... assessed for APTT, prothrombin %, prothrombin time (PT) and thrombin time, fibrinogen, D-dimer ... platelet count, and the thrombodynamic test parameters (V/Vi/Vst, Tlag, Cs, D). Results: Significant differences ... were observed in the thrombin time, D-dimer, platelet count, and the thrombodynamic parameters of V/Vst ...

Abstract	Background: At the present moment, an urgent and unresolved problem is the search for a method to diagnose disorders of the hemostasis system in patients with the new coronavirus infection. The integral tests, in particular, the thrombodynamics test, will presumably make it possible to monitor changes in blood clotting, and predict the course of the disease in patients with COVID-19. Aims: To comparatively assess the plasma hemostasis parameters and results of the thrombodynamics test in patients with COVID-19 viral infection of different severity. Methods: The study included 96 patients with a confirmed diagnosis of COVID-19, admitted to a hospital for infectious diseases on the base of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology in the period from April 23, 2020, to June 20, 2020, and discharged at the end of treatment. SARS-CoV-2 was identified by PCR. The patients were stratified by the severity into 3 groups: mild course (n=25), moderate course (n=54), severe course (n=17). The diagnostics and treatment of patients were carried out in accordance with the Temporary Methodological Recommendations of the Ministry of Health of the Russian Federation for the prevention, diagnosis and treatment of the new coronavirus infection, versions 5, 6, 7. In the course of the treatment, the patients were assessed for APTT, prothrombin %, prothrombin time (PT) and thrombin time, fibrinogen, D-dimer, platelet count, and the thrombodynamic test parameters (V/Vi/Vst, Tlag, Cs, D). Results: Significant differences were observed in the thrombin time, D-dimer, platelet count, and the thrombodynamic parameters of V/Vst, Cs, and D taken before admission and a week after admission. We found a relationship between the parameters of hemostasis (fibrinogen concentration, PT, prothrombin %, APTT, Tlag, D) and the duration of hospital stay. There was a positive relationship between the content of fibrinogen and D (r=0.6307, p 0.0001) and a strong positive relationship between PT and Tlag ...
Keywords	covid-19 ; hemostasis ; d-dimer ; blood coagulation ; Medicine ; R
Subject code	610
Language	Russian
Publishing date	2021-12-01T00:00:00Z
Publisher	Eco-vector
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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