Microbiology Independent Research Journal (MIR Journal)
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Давление отбора на ген нейраминидазы вирусов гриппа, выделенных в Украине с 2009 по 2015 гг
A broad range of naturally occurring antigenic variants of the influenza virus is caused by its rapid evolutionary variability. The survival of viable influenza virus variants occurs through natural selection. Treatment of influenza infection with modern antiviral drugs – neuraminidase (NA) inhibitors – leads to occurrence of mutations in the NA gene, which result in emergence of virus resistance to these drugs. The goal of this study was to determine the selection pressure on the NA protein of influenza viruses isolated in Ukraine from 2009 to 2015. The main method for assessing the evolutionary pressure on proteins is to quantify the ratio of substitution rates at nonsynonymous (dN) and synonymic (dS) sites. With the help of this method we showed that only a few codons in the NA gene were under the positive selection resulting in mutations at the following sites: for influenza A viruses of A(H1N1)pdm09 subtype – site 40, for viruses of A(H3N2) subtype – sites 93 and 402, for B/Yamagata lineage viruses – sites 74, 99, and 268, and for the B/Victoria lineage viruses – sites 358, 288, and 455. These sites are not associated with NA active site, transmembrane domain, or the antigenic sites of this protein. We concluded that NA inhibitors are not a significant factor in the process of selection of the influenza viruses in Ukraine because sites associated with the resistance of influenza viruses to NA inhibitors were not affected by positive selection. This finding could be explained by the limited use of NA inhibitors for the treatment of influenza infections in Ukraine.Большое разнообразие существующих в природе антигенных вариантов вируса гриппа вызвано его быстрой эволюционной изменчивостью. Отбор жизнеспособных вариантов вируса гриппа происходит за счет естественного отбора. Лечение гриппозной инфекции с помощью современных противовирусных препаратов – ингибиторов нейраминидазы (NA) – приводит к возникновению мутаций в гене NA, которые ведут к появлению резистентности вирусов к данным препаратам. Цель работы состояла в определении давления отбора на белок NA вирусов гриппа, выделенных в Украине в период с 2009 по 2015 год. Основным методом оценки эволюционного давления на белки является определение количественного соотношения частот замен в несинонимических (dN) и синонимических сайтах (dS). С помощью этого метода мы показали, что лишь некоторые кодоны в гене NA были под влиянием положительного отбора: для вирусов гриппа типа А подтипа A(H1N1)pdm09 – сайт 40, для вирусов подтипа A(H3N2) – сайты 93 и 402, для вирусов гриппа типа B разновидности B/Yamagata – сайты 74, 99 и 268, и для вирусов разновидности В/Victoria – сайты 358, 288 и 455. Указанные сайты не связаны ни с активным центром NA, ни с трансмембранным доменом, ни с антигенными сайтами. Ингибиторы NA не являются селективным фактором отбора вирусов гриппа в Украине, поскольку, сайты, ассоциированные с резистентностью вирусов гриппа к ингибиторам NA, не попали под влияние положительного отбора, что, вероятно, объясняется низким уровнем применения данных противовирусных препаратов в Украине
Синтез и исследование противомикробной активности производных нифуроксазида
The number of infections caused by microorganisms that are resistant to antibiotics and synthetic antibacterial drugs is growing fast worldwide. This is one of the most important and urgent problems in health care. The main efforts of researchers around the world are focused on solving this issue. Nitrofurans represent one of the most effective classes of antibacterial drugs. We have synthesized 4 analogues of nifuroxazide – a well known nitrofuran antibiotic – and confirmed their structures by NMR, IR spectroscopy, and mass-spectrometry. All of the obtained compounds were studied for antimicrobial and antifungal activity. Activity against Escherichia coli, Staphylococcus aureus, Staphylococcus haemolyticus, and Pseudomonas aeruginosa was evaluated by the agar diffusion method. The synthesized compounds suppressed the growth of all the studied bacterial strains except Escherichia coli; the diameter of the inhibition zones ranged from 13.5 to 28 mm depending on the concentration of the tested compound and bacterial strain. One of the compounds studied in this project – the pyridine analogue of nifuroxazide – exceeded the activity of the standard (nifuroxazide) against the Staphylococcus aureus. The inhibitory activity of the synthesized compounds against the Candida albicans and Cryptococcus neoformans yeasts was determined using the microdilution method. The results were assessed according to the indicator color change. None of the studied compounds showed activity against these cultures. The obtained results confirm that substituted nifuroxazides have significant antimicrobial activity and, therefore, can be considered as promising candidates for developing new antibacterial drugs.В связи с постоянно растущим числом инфекций, вызываемых устойчивыми к синтетическим антибактериальным препаратам и антибиотикам микроорганизмами, основные усилия исследователей всего мира направлены на решение данной проблемы. Одним из самых эффективных среди антибактериальных препаратов является класс замещенных нитрофуранов. Синтезированы 4 аналога нифуроксазида (представителя нитрофуранового ряда), структура которых подтверждена с помощью ЯМР, ИК спектроскопии и масс-спектрометрии. Все полученные соединения изучены на противомикробную и противогрибковую активность. Активность по отношению к бактериям Escherichia coli, Staphylococcus aureus, Staphylococcus haemolyticus и Pseudomonas aeruginosa оценивали методом диффузии в агар. Полученные вещества подавляли рост всех исследованных штаммов бактерий, кроме Escherichia coli; диаметр зон ингибирования находился в пределах от 13.5 до 28 мм в зависимости от концентрации исследуемого вещества и штамма бактерий. Одно из изученных в этой работе соединений – пиридиновый аналог нифуроксазида – превзошло по активности стандарт (нифуроксазид) по отношению к Staphylococcus aureus и поэтому может считаться перспективным соединением для разработки новых антибактериальных средств. Определение ингибирующей активности синтезированных препаратов по отношению к дрожжевым грибам Candida albicans и Cryptococcus neoformans проводили с помощью метода последовательных разведений с оценкой эффекта по изменению окраски индикатора. Ни одно из полученных соединений не проявило активности в отношении данных культур. Полученные результаты подтверждают, что замещенные аналоги нифуроксазида обладают противомикробной активностью и являются перспективными кандидатами для разработки новых антибактериальных средств
Synthesis and study of the antimicrobial activity of nifuroxazide derivatives
The number of infections caused by microorganisms that are resistant to antibiotics and synthetic antibacterial drugs is growing fast worldwide. This is one of the most important and urgent problems in health care. The main efforts of researchers around the world are focused on solving this issue. Nitrofurans represent one of the most effective classes of antibacterial drugs. We have synthesized 4 analogues of nifuroxazide – a well known nitrofuran antibiotic – and confirmed their structures by NMR, IR spectroscopy, and mass-spectrometry. All of the obtained compounds were studied for antimicrobial and antifungal activity. Activity against Escherichia coli, Staphylococcus aureus, Staphylococcus haemolyticus, and Pseudomonas aeruginosa was evaluated by the agar diffusion method. The synthesized compounds suppressed the growth of all the studied bacterial strains except Escherichia coli; the diameter of the inhibition zones ranged from 13.5 to 28 mm depending on the concentration of the tested compound and bacterial strain. One of the compounds studied in this project – the pyridine analogue of nifuroxazide – exceeded the activity of the standard (nifuroxazide) against the Staphylococcus aureus. The inhibitory activity of the synthesized compounds against the Candida albicans and Cryptococcus neoformans yeasts was determined using the microdilution method. The results were assessed according to the indicator color change. None of the studied compounds showed activity against these cultures. The obtained results confirm that substituted nifuroxazides have significant antimicrobial activity and, therefore, can be considered as promising candidates for developing new antibacterial drugs.The number of infections caused by microorganisms that are resistant to antibiotics and synthetic antibacterial drugs is growing fast worldwide. This is one of the most important and urgent problems in health care. The main efforts of researchers around the world are focused on solving this issue. Nitrofurans represent one of the most effective classes of antibacterial drugs. We have synthesized 4 analogues of nifuroxazide – a well known nitrofuran antibiotic – and confirmed their structures by NMR, IR spectroscopy, and mass-spectrometry. All of the obtained compounds were studied for antimicrobial and antifungal activity. Activity against Escherichia coli, Staphylococcus aureus, Staphylococcus haemolyticus, and Pseudomonas aeruginosa was evaluated by the agar diffusion method. The synthesized compounds suppressed the growth of all the studied bacterial strains except Escherichia coli; the diameter of the inhibition zones ranged from 13.5 to 28 mm depending on the concentration of the tested compound and bacterial strain. One of the compounds studied in this project – the pyridine analogue of nifuroxazide – exceeded the activity of the standard (nifuroxazide) against the Staphylococcus aureus. The inhibitory activity of the synthesized compounds against the Candida albicans and Cryptococcus neoformans yeasts was determined using the microdilution method. The results were assessed according to the indicator color change. None of the studied compounds showed activity against these cultures. The obtained results confirm that substituted nifuroxazides have significant antimicrobial activity and, therefore, can be considered as promising candidates for developing new antibacterial drugs
The selection pressure on the neuraminidase gene of influenza viruses isolated in Ukraine from 2009 to 2015
A broad range of naturally occurring antigenic variants of the influenza virus is caused by its rapid evolutionary variability. The survival of viable influenza virus variants occurs through natural selection. The treatment of influenza infection with modern antiviral drugs – neuraminidase (NA) inhibitors – leads to the occurrence of mutations in the NA gene, which thereby result in the emergence of virus resistance to these drugs. The goal of this study was to determine the selection pressure on the NA protein of influenza viruses isolated in Ukraine from 2009 to 2015. The main method for assessing the selection pressure on proteins is to quantify the ratio of substitution rates at nonsynonymous (dN) and synonymous (dS) sites. With the help of this method, we showed that only a few codons in the NA gene were under positive selection resulting in mutations at the following sites: for influenza A viruses of the A(H1N1)pdm09 subtype – site 40, for viruses of the A(H3N2) subtype – sites 93 and 402, for Influenza B viruses of the B/Yamagata lineage – sites 74, 99, and 268, and for the viruses of the B/Victoria lineage – sites 358, 288, and 455. These sites are not associated with the NA active site, transmembrane domain, or the antigenic sites of this protein. We concluded that NA inhibitors are not a significant factor in the process of selection of the influenza viruses in Ukraine because the sites associated with the resistance of influenza viruses to NA inhibitors were not affected by positive selection. This finding could be explained by the limited use of NA inhibitors for the treatment of influenza infections in Ukraine. A broad range of naturally occurring antigenic variants of the influenza virus is caused by its rapid evolutionary variability. The survival of viable influenza virus variants occurs through natural selection. The treatment of influenza infection with modern antiviral drugs – neuraminidase (NA) inhibitors – leads to the occurrence of mutations in the NA gene, which thereby result in the emergence of virus resistance to these drugs. The goal of this study was to determine the selection pressure on the NA protein of influenza viruses isolated in Ukraine from 2009 to 2015. The main method for assessing the selection pressure on proteins is to quantify the ratio of substitution rates at nonsynonymous (dN) and synonymous (dS) sites. With the help of this method, we showed that only a few codons in the NA gene were under positive selection resulting in mutations at the following sites: for influenza A viruses of the A(H1N1)pdm09 subtype – site 40, for viruses of the A(H3N2) subtype – sites 93 and 402, for Influenza B viruses of the B/Yamagata lineage – sites 74, 99, and 268, and for the viruses of the B/Victoria lineage – sites 358, 288, and 455. These sites are not associated with the NA active site, transmembrane domain, or the antigenic sites of this protein. We concluded that NA inhibitors are not a significant factor in the process of selection of the influenza viruses in Ukraine because the sites associated with the resistance of influenza viruses to NA inhibitors were not affected by positive selection. This finding could be explained by the limited use of NA inhibitors for the treatment of influenza infections in Ukraine.
Клеточный иммунный ответ у инфицированных животных против белка NSP, кодируемого негативной цепью NS RNA вируса гриппа А
Influenza A virus belongs to a family of enveloped viruses with an RNA genome of negative polarity consisting of 8 RNA segments. The transcription of this RNA genome results in the synthesis of positive-sense mRNAs that translate up to 16 unique viral proteins with the help of splicing and translational shift mechanisms. The 8th NS segment encodes the NS1 protein (27 kDa), which is an active interferon antagonist, and the nuclear export protein NEP (14 kDa) through the standard negative polarity pathway. In addition, an alternative open reading frame for the synthesis of a third viral protein (NSP, negative-strand protein) by means of a direct translation of genome polarity RNA (the so-called positive polarity genome strategy) was identified in the NS segment. Since it is unknown as to whether the NSP protein can be synthesized in the infected organism post viral infection, the generation of spleen leucocytes specific to this protein was studied in mice after two sequential infections with influenza A viruses of H1N1 and H3N2 subtypes. It was found that leucocyte clones specifically recognizing a peptide domain in the central region of the NSP protein (amino acid positions 82-119) were generated in mice infected with influenza A viruses. In silico prediction has shown strong major histocompatibility complex-1 (MHC-I) and MHC-II specific epitopes in this central domain of the NSP. Comparative analysis of the influenza H3N2 viruses circulating in humans during 1968-2018 has shown high NSP variability, which was similar to that shown for the hemagglutinin (HA) and neuraminidase (NA) proteins. The highest variability was found to be in the N- and C-terminal parts of the NSP. These observations suggest that synthesis of the NSP protein occurs in infected animals and further support a bipolar (ambisense) strategy of the RNA genome of human influenza A virus.Вирус гриппа А относится к оболочечным RNA-содержащим вирусам с негативно-полярным геномом, состоящим из 8 сегментов RNA, каждый из которых является матрицей для синтеза позитивно-полярных mRNA, которые, в свою очередь, служат матрицей для синтеза 16 вирусных белков с использованием для некоторых механизма сплайсинга или трансляционного шифта. Восьмой сегмент NS посредством классической негативной стратегии генома кодирует белок NS1, обладающий анти-интерфероновой активностью (27 кДа), и белок ядерного экспорта NEP (NS2) (nuclear export protein, 14 кДа). Кроме этого, в сегменте NS обнаружена дополнительная открытая рамка для синтеза третьего вирусного белка по альтернативному пути посредством прямой трансляции негативно полярной вирусной RNA. Эта стратегия генома получила название позитивно-полярной. Образование данного белка, названного NSP (negative strand protein), при инфекции вируса гриппа А в целостном организме пока не обнаружено. Анализ белка NSP in silico выявил наличие доменов MHC-I (major histocompatibility complex-1) и MHC-II. Сравнительный анализ вирусов гриппа подтипа H3N2, циркулировавших среди людей в период с 1968 по 2018 гг., показал высокую изменчивость гена белка NSP, которая сходна с изменчивостью поверхностных белков гемагглютинина (HA) и нейраминидазы (NA). Наибольшая изменчивость обнаруживалась в зонах, соответствующих N- и C-концевым участкам белка NSP. В настоящей работе изучена возможность образования иммунных лейкоцитов, специфичных к белку NSP, у мышей после инфекции вирусом гриппа А. Показано, что у мышей после заражения последовательно двумя вирусами гриппа А разных сероподтипов обнаруживаются иммунные лейкоциты, специфически распознающие вирусные домены в центральной зоне белка NSP (позиции аминокислот 82-119). Полученные данные с большой вероятностью позволяют утверждать, что при инфекции вирусом гриппа А в организме животных имеет место экспрессия гена NSP, что в свою очередь подтверждает концепцию о биполярной (амбисенс) стратегии генома вируса гриппа А
Cellular immune response in infected mice to NSP protein encoded by the negative strand NS RNA of influenza A virus
Influenza A virus belongs to a family of enveloped viruses with an RNA genome of negative polarity consisting of 8 RNA segments. The transcription of this RNA genome results in the synthesis of positive-sense mRNAs that translate up to 16 unique viral proteins with the help of splicing and translational shift mechanisms. The 8th NS segment encodes the NS1 protein (27 kDa), which is an active interferon antagonist, and the nuclear export protein NEP (14 kDa) through the standard negative polarity pathway. In addition, an alternative open reading frame for the synthesis of a third viral protein (NSP, negative-strand protein) by means of a direct translation of genome polarity RNA (the so-called positive polarity genome strategy) was identified in the NS segment. Since it is unknown as to whether the NSP protein can be synthesized in the infected organism post viral infection, the generation of spleen leucocytes specific to this protein was studied in mice after two sequential infections with influenza A viruses of H1N1 and H3N2 subtypes. It was found that leucocyte clones specifically recognizing a peptide domain in the central region of the NSP protein (amino acid positions 82-119) were generated in mice infected with influenza A viruses. In silico prediction has shown strong major histocompatibility complex-1 (MHC-I) and MHC-II specific epitopes in this central domain of the NSP. Comparative analysis of the influenza H3N2 viruses circulating in humans during 1968-2018 has shown high NSP variability, which was similar to that shown for the hemagglutinin (HA) and neuraminidase (NA) proteins. The highest variability was found to be in the N- and C-terminal parts of the NSP. These observations suggest that synthesis of the NSP protein occurs in infected animals and further support a bipolar (ambisense) strategy of the RNA genome of human influenza A virus.Influenza A virus belongs to a family of enveloped viruses with an RNA genome of negative polarity consisting of 8 RNA segments. The transcription of this RNA genome results in the synthesis of positive-sense mRNAs that translate up to 16 unique viral proteins with the help of splicing and translational shift mechanisms. The 8th NS segment encodes the NS1 protein (27 kDa), which is an active interferon antagonist, and the nuclear export protein NEP (14 kDa) through the standard negative polarity pathway. In addition, an alternative open reading frame for the synthesis of a third viral protein (NSP, negative-strand protein) by means of a direct translation of genome polarity RNA (the so-called positive polarity genome strategy) was identified in the NS segment. Since it is unknown as to whether the NSP protein can be synthesized in the infected organism post viral infection, the generation of spleen leucocytes specific to this protein was studied in mice after two sequential infections with influenza A viruses of H1N1 and H3N2 subtypes. It was found that leucocyte clones specifically recognizing a peptide domain in the central region of the NSP protein (amino acid positions 82-119) were generated in mice infected with influenza A viruses. In silico prediction has shown strong major histocompatibility complex-1 (MHC-I) and MHC-II specific epitopes in this central domain of the NSP. Comparative analysis of the influenza H3N2 viruses circulating in humans during 1968-2018 has shown high NSP variability, which was similar to that shown for the hemagglutinin (HA) and neuraminidase (NA) proteins. The highest variability was found to be in the N- and C-terminal parts of the NSP. These observations suggest that synthesis of the NSP protein occurs in infected animals and further support a bipolar (ambisense) strategy of the RNA genome of human influenza A virus
Efficient soluble expression and purification of influenza A and B nucleoproteins in E. coli
Viral nucleoprotein (NP) is an abundant essential protein of an influenza virus that has important functional and structural roles. It participates in genomic organization, nuclear trafficking, RNA transcription, and genome replication. From the research point of view, NP is an important protein that is used in the development of new diagnostic methods and vaccination protocols. NP is a promising target for antiviral chemotherapeutic drugs as well. Successful expression of codon-optimized NP genes in E. coli has been reported. In this study, we demonstrated the efficient expression and purification of soluble NPs of influenza A and B viruses in E. coli without the codon-optimization of DNA sequences. This procedure preserves the co-translational protein folding, protein configuration and function. Obtained NPs of influenza A and B viruses were monomers and reacted well with mouse specific antibodies according to Western blot analysis. Our results show that both influenza A and influenza B virus NPs can be efficiently expressed in E. coli without codon-optimization.Viral nucleoprotein (NP) is an abundant essential protein of an influenza virus that has important functional and structural roles. It participates in genomic organization, nuclear trafficking, RNA transcription, and genome replication. From the research point of view, NP is an important protein that is used in the development of new diagnostic methods and vaccination protocols. NP is a promising target for antiviral chemotherapeutic drugs as well. Successful expression of codon-optimized NP genes in E. coli has been reported. In this study, we demonstrated the efficient expression and purification of soluble NPs of influenza A and B viruses in E. coli without the codon-optimization of DNA sequences. This procedure preserves the co-translational protein folding, protein configuration and function. Obtained NPs of influenza A and B viruses were monomers and reacted well with mouse specific antibodies according to Western blot analysis. Our results show that both influenza A and influenza B virus NPs can be efficiently expressed in E. coli without codon-optimization
Interference plasmids and their use in combating bacterial resistance
Fighting against pathogenic bacteria that are resistant to antibiotics has become critical for health care worldwide. More than half a million people die every year from infections caused by drug resistant bacteria. Since bacteria acquire resistance to antibiotics very quickly and the development of new antibiotics is a lengthy process, the search for new approaches to stop the spread of bacterial resistance is extremely important. The spread of antibiotic resistance is accomplished mainly by horizontal gene transfer. Scientists are concentrating their efforts on studying the mechanism of this process in order to find a way to stop or reverse it. In this paper, the author gives a brief review of the recent studies on horizontal gene transfer, particularly on incompatibility-based plasmid curing systems. The author examines new possibilities to use the mechanism of horizontal gene transfer for the developing of novel approaches to fight pathogenic bacteria.Fighting against pathogenic bacteria that are resistant to antibiotics has become critical for health care worldwide. More than half a million people die every year from infections caused by drug resistant bacteria. Since bacteria acquire resistance to antibiotics very quickly and the development of new antibiotics is a lengthy process, the search for new approaches to stop the spread of bacterial resistance is extremely important. The spread of antibiotic resistance is accomplished mainly by horizontal gene transfer. Scientists are concentrating their efforts on studying the mechanism of this process in order to find a way to stop or reverse it. In this paper, the author gives a brief review of the recent studies on horizontal gene transfer, particularly on incompatibility-based plasmid curing systems. The author examines new possibilities to use the mechanism of horizontal gene transfer for the developing of novel approaches to fight pathogenic bacteria
Разработка лекарств и открытый доступ: подходы и перспективы
The development of a new medicine is a process that requires enormous time and tremendous financing. It takes 10-15 years from the discovery of an active compound to the launch of its production and the start of drug marketing with the total costs of the project reaching 1.8 billion US dollars. These large time and financial costs stem from repeated testing and elimination of a large percentage of compounds over the course of screening at each stage of preclinical and clinical trials. Many investors have lost interest in financing new drug discovery projects (or pharmaceutical start-up companies) due to the high risk and extensive time required to produce a return on investments. Since all the research data are considered confidential by pharmaceutical companies and thus never shared with scientific community, different scientific groups waste significant resources repeating the same costly experiments in drug discovery. In this article, we discuss new approaches to drug discovery involving open access to the research data and alternative financing that could significantly streamline the search for new cures for human diseases.Разработка нового лекарства – процесс, требующий колоссальных затрат времени и финансовых средств. От нахождения активных химических соединений до выхода препарата на рынок проходит 10-15 лет и расходуется порядка 1.8 миллиарда долларов. Такие сроки и суммы обусловлены большим процентом отсева химических соединений на каждой стадии доклинических и клинических испытаний. Многие инвесторы потеряли интерес к финансированию фармацевтических стартапов и проектов по разработке новых препаратов из-за высокого риска и продолжительного времени, необходимого для получения прибыли от инвестиций. Поскольку все результаты исследований принадлежат фармацевтическим компаниям, считаются конфиденциальными и поэтому недоступны для научного сообщества, научные коллективы тратят значительные ресурсы, повторяя одни и те же дорогостоящие эксперименты. В этом обзоре мы рассматриваем современные принципы организации работы по созданию новых лекарств – открытый доступ к результатам исследований и альтернативное финансирование. Применение этих принципов позволит значительно упростить и удешевить поиск новых лекарственных препаратов для лечения людей
The problem of bacterial complications post respiratory viral infections
Every person over the course of their lifetime is repeatedly infected by a variety of respiratory viruses that represent risk factors for the development of bacterial complications. The most dangerous among the etiological factors of acute respiratory viral diseases is the influenza A virus. This virus is capable of causing catastrophic pandemics with high mortality mainly due to secondary bacterial pneumonia. As has been shown in numerous recent studies, the main mechanism of provoking bacterial infections irrespective of the type of respiratory virus is the imbalanced response of the antiviral innate immunity – excessive interferon response and uncontrolled inflammation. The probability of severe bacterial complications in the course of acute respiratory viral infections is determined by both the virulence of the virus itself and by the composition of the respiratory microbiota at the time of the viral infection as well as by the genetic characteristics of the organism. The occurrence of severe bacterial complications is also affected by the chronic diseases that have an impact on the regulation of the innate immune response. This review summarizes the current concept of the mechanisms of the development of post viral bacterial complications as well as the potential prevention strategies for these complications.Every person over the course of their lifetime is repeatedly infected by a variety of respiratory viruses that represent risk factors for the development of bacterial complications. The most dangerous among the etiological factors of acute respiratory viral diseases is the influenza A virus. This virus is capable of causing catastrophic pandemics with high mortality mainly due to secondary bacterial pneumonia. As has been shown in numerous recent studies, the main mechanism of provoking bacterial infections irrespective of the type of respiratory virus is the imbalanced response of the antiviral innate immunity – excessive interferon response and uncontrolled inflammation. The probability of severe bacterial complications in the course of acute respiratory viral infections is determined by both the virulence of the virus itself and by the composition of the respiratory microbiota at the time of the viral infection as well as by the genetic characteristics of the organism. The occurrence of severe bacterial complications is also affected by the chronic diseases that have an impact on the regulation of the innate immune response. This review summarizes the current concept of the mechanisms of the development of post viral bacterial complications as well as the potential prevention strategies for these complications