scholarly journals Nucleosides for the treatment of respiratory RNA virus infections

2018 ◽  
Vol 26 ◽  
pp. 204020661876448 ◽  
Author(s):  
Paul C Jordan ◽  
Sarah K Stevens ◽  
Jerome Deval

Influenza virus, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, coronaviruses, and rhinoviruses are among the most common viruses causing mild seasonal colds. These RNA viruses can also cause lower respiratory tract infections leading to bronchiolitis and pneumonia. Young children, the elderly, and patients with compromised cardiac, pulmonary, or immune systems are at greatest risk for serious disease associated with these RNA virus respiratory infections. In addition, swine and avian influenza viruses, together with severe acute respiratory syndrome-associated and Middle Eastern respiratory syndrome coronaviruses, represent significant pandemic threats to the general population. In this review, we describe the current medical need resulting from respiratory infections caused by RNA viruses, which justifies drug discovery efforts to identify new therapeutic agents. The RNA polymerase of respiratory viruses represents an attractive target for nucleoside and nucleotide analogs acting as inhibitors of RNA chain synthesis. Here, we present the molecular, biochemical, and structural fundamentals of the polymerase of the four major families of RNA respiratory viruses: Orthomyxoviridae, Pneumoviridae/Paramyxoviridae, Coronaviridae, and Picornaviridae. We summarize past and current efforts to develop nucleoside and nucleotide analogs as antiviral agents against respiratory virus infections. This includes molecules with very broad antiviral spectrum such as ribavirin and T-705 (favipiravir), and others targeting more specifically one or a few virus families. Recent advances in our understanding of the structure(s) and function(s) of respiratory virus polymerases will likely support the discovery and development of novel nucleoside analogs.

Author(s):  
Sinha Pranay ◽  
Katherine Reifler ◽  
Michael Rossi ◽  
Manish Sagar

Abstract Detection of diverse respiratory viruses in Boston was around 80% lower after practices were instituted to limit COVID-19 spread compared to the same time period during the previous five years. Continuing the strategies that lower COVID-19 dissemination may be useful in decreasing the incidence of other viral respiratory infections.


2021 ◽  
Author(s):  
Sorush Niknamian

Background: A virus is a small infectious agent that replicates only inside the living cells of an organism. Viruses can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea. In evolution, viruses are an important means of horizontal gene transfer, which increases genetic diversity in a way analogous to sexual reproduction. Influenza (Including (COVID-19), is an infectious disease caused by an influenza virus. Some viruses especially smallpox, throughout history, has killed between 300-500 million people in its 12,000year existence. As modern humans increased in numbers, new infectious diseases emerged, including SARS-CoV-2. We have two groups of virus, RNA and DNA viruses. The most brutal viruses are RNA ones like COVID-19 (Sars-CoV-2 [1] Introduction: Coronaviruses are a group of viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respiratory tract infections that are typically mild, such as some cases of the common cold (among other possible causes, predominantly rhinoviruses), though rarer forms can be lethal, such as SARS, MERS, and COVID-19. Symptoms vary in other species: in chickens, they cause an upper respiratory tract disease, while in cows and pigs they cause diarrhea. Coronaviruses constitute the subfamily Orthocoronavirinae, The genome size, coronaviruses ranges from approximately 27 to 34 kilobases, the largest among known RNA viruses. Discussions and Results: We have researched from the first virus in the planet to the last mutated version which is SARS-COV-2. We have collected many informative data in tables and figures to reach the main cause of 2019Coronavirus and calculated the probability and estimated deaths in the current time. We have discussed about the possible treatment and prevention of the virus and did algebraic calculations on the epidemiology, the size and even the future of this pandemic. The only era which any virus had not been epidemic, were through world war 2, were the German scientists had found the way to fight any viral infections which is very important and can help scientists to reach the main treatment of the new 2019-Coronavirus. We have sorted the deadly and non-deadly coronaviruses and explained how this epidemic had begun through Evolutionary Medicine (EM). The result of the article is that 16% of the whole population in the world has been contaminated which is 1248000000 of 7.8 billion people world-wide. SARS-CoV-2 is an RNA Virus. its nucleic acid is 2 single-stranded RNA (ssRNA). The polarity of this virus is positive-sense ((+) ssRNA). Positivesense viral RNA is similar to mRNA and thus can be immediately translated by the host cell. Recombination in RNA viruses appears to be an adaptation for coping with genome damage. Recombination can occur infrequently between animal viruses of the same species but of divergent lineages. The resulting recombinant viruses may sometimes cause an outbreak of infection in humans. RNA viruses have very high mutation rates This is one reason why it is difficult to make effective vaccines to prevent diseases caused by RNA viruses. The resulting recombinant viruses causes an outbreak of infection in humans. Conclusion: In conclusion, the mutation of the SARSCoV and influenza viruses through Drift and Reassortment is the main cause of SARS-CoV-2 through natural selection, Lamarckian Evolution and coevolution which caused this RNA virus so powerful, unpredicted and different in the genome size and nations worldwide. The first Pandemic of Influenza was first detected in 1732 and this virus evolved through natural selection till 2019 which caused the worldwide pandemic of SARS-CoV-2. Based on many studies, inhalation of Ozone plus Sulfur Dioxide, increasing the amounts of L-Glutathione (Which is low in children and older adults and this is the main reason why older adults and children die from this disease.) plus Viral Phage Therapy (VPT) which we discussed fully in this article can be the possible prime treatment of SARS-CoV-2 infection. The seasonal temperature cannot be useful in controlling/reducing the pandemic of this virus since the natural selection, Lamarckian Evolution and high mutation of the virus helps its survival. No antiviral drugs will be useful against SARSCoV-2 because of high rate of mutation and primarily adaptation of the virus to the drugs and even the environmental Temperature.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eteri Regis ◽  
Sara Fontanella ◽  
Lijing Lin ◽  
Rebecca Howard ◽  
Sadia Haider ◽  
...  

AbstractThe mechanisms explaining excess morbidity and mortality in respiratory infections among males are poorly understood. Innate immune responses are critical in protection against respiratory virus infections. We hypothesised that innate immune responses to respiratory viruses may be deficient in males. We stimulated peripheral blood mononuclear cells from 345 participants at age 16 years in a population-based birth cohort with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2) and investigated sex differences in interferon (IFN) responses. IFN-α responses to all viruses and stimuli were 1.34–2.06-fold lower in males than females (P = 0.018 −  < 0.001). IFN-β, IFN-γ and IFN-induced chemokines were also deficient in males across all stimuli/viruses. Healthcare records revealed 12.1% of males and 6.6% of females were hospitalized with respiratory infections in infancy (P = 0.017). In conclusion, impaired innate anti-viral immunity in males likely results in high male morbidity and mortality from respiratory virus infections.


2018 ◽  
Vol 5 (4) ◽  
pp. 151
Author(s):  
Jelle J. Feddema ◽  
Eric Claassen

<p class="abstract"><strong>Background:</strong> Respiratory tract infections (RTIs) pose a significant burden on health systems worldwide. Progress has been booked in reducing RTI disease burden through development of diagnostics, therapeutics and vaccines, though most efforts often fail to address the contribution of non-influenza viruses. Increasing awareness and the prevailing unmet need has resulted in the establishment of initiatives that aim to explore ways in which to extend innovation efforts for influenza to the broad range of respiratory viruses. This study will provide a detailed description of the state of the RTI market in Asia.</p><p class="abstract"><strong>Methods:</strong> By developing a dataset containing data from patent documents and clinical trials (CTs) we aimed to provide a detailed description of the RTI market in Asia.</p><p class="abstract"><strong>Results:</strong> We found a downward patent filing trend in respiratory diagnostics but a high number of phase 3 studies. A strong preference for the development of therapeutics and vaccines targeting bacterial pneumonia and influenza became apparent, whereas less attention is given towards product development targeting non-influenza viruses.</p><p class="abstract"><strong>Conclusions: </strong>The findings indicate a mature respiratory diagnostics market with minor industrial interest but at the same time an evolving RTI CT market with a strong late-stage pipeline. Asia represents only a handful of studies related to non-influenza viruses, mostly conducted by non-profit organisations. The business segment appears to focus upon product development for more profitable respiratory infections thereby suggesting that involvement and engagement of the industry within global initiatives and efforts to increase innovation for non-influenza viruses is not optimal.</p>


2014 ◽  
Vol 1 (2) ◽  
Author(s):  
Rodica Gilca ◽  
Rachid Amini ◽  
Monique Douville-Fradet ◽  
Hugues Charest ◽  
Josée Dubuque ◽  
...  

Background.  During peak weeks of seasonal influenza epidemics, severe respiratory infections without laboratory confirmation are typically attributed to influenza. Methods.  In this prospective study, specimens and demographic and clinical data were collected from adults admitted with respiratory symptoms to 4 hospitals during the 8–10 peak weeks of 2 influenza seasons. Specimens were systematically tested for influenza and 13 other respiratory viruses (ORVs) by using the Luminex RVP FAST assay. Results.  At least 1 respiratory virus was ide.jpegied in 46% (21% influenza, 25% noninfluenza; 2% coinfection) of the 286 enrolled patients in 2011–2012 and in 62% (46% influenza, 16% noninfluenza; 3% coinfection) of the 396 enrolled patients in 2012–2013. Among patients aged ≥75 years, twice as many ORVs (32%) as influenza viruses (14%) were detected in 2011–2012. During both seasons, the most frequently detected ORVs were enteroviruses/rhinoviruses (7%), respiratory syncytial virus (6%), human metapneumovirus (5%), coronaviruses (4%), and parainfluenza viruses (2%). Disease severity was similar for influenza and ORVs during both seasons. Conclusions.  Although ORV contribution relative to influenza varies by age and season, during the peak weeks of certain influenza seasons, ORVs may be a more frequent cause of elderly hospitalization than influenza.


2006 ◽  
Vol 194 (9) ◽  
pp. 1283-1290 ◽  
Author(s):  
A. Manning ◽  
V. Russell ◽  
K. Eastick ◽  
G. H. Leadbetter ◽  
N. Hallam ◽  
...  

Abstract BackgroundHuman bocavirus (HBoV) and PARV4 are newly discovered human parvoviruses. HBoV, which was first detected in respiratory samples, has a potential role in the development of human respiratory disease. The present study compared the frequencies, epidemiological profiles, and clinical backgrounds of HBoV and PARV4 infections with those of other respiratory virus infections, by evaluating diagnostic samples referred to the Specialist Virology Laboratory (SVL) at the Royal Infirmary of Edinburgh (Edinburgh, United Kingdom) MethodsAnonymized samples and study subject information were obtained from the respiratory sample archive of the SVL. Samples were screened for HBoV, PARV4, B19, respiratory syncytial virus (RSV), adenoviruses, influenza viruses, and parainfluenza viruses by use of nested polymerase chain reaction ResultsHBoV infection was detected in 47 (8.2%) of 574 study subjects,&amp;ranking third in prevalence behind RSV infection (15.7%) and adenovirus infection (10.3%). Peak incidences of HBoV were noted among infants and young children (age, 6–24 months) during the midwinter months (December and January) and were specifically associated with lower respiratory tract infections. HBoV infections were frequently accompanied by other respiratory viruses (frequency, 43%), and they were more prevalent among individuals infected with other respiratory viruses (17%), frequently adenovirus or RSV. All respiratory samples were negative for PARV4 ConclusionsIn the present study, HBoV was a frequently detected, potential respiratory pathogen, with a prevalence and an epidemiological profile comparable to those of RSV. Identification of HBoV infections may be clinically important in the future


2021 ◽  
Vol 15 (1) ◽  
pp. 32
Author(s):  
Diana Perez-SanJose ◽  
Miguel Angel de la Fuente ◽  
Julia Serna Pérez ◽  
Maria Simarro ◽  
José María Eiros Bouza ◽  
...  

Influenza viruses provide a great threat for the human population, causing highly contagious respiratory infections that can lead to serious clinical complications. There are a limited variety of influenza antivirals, and these antivirals are subjected to the constant emergence of resistances. Therefore, the development of new antiviral strategies to combat influenza viruses and other RNA viruses must be promoted. In this work, we design a proof-of-concept of a recently described CRISPR/Cas tool that has been proposed as a possible future RNA virus antiviral, named CRISPR/CasRx. For this, we verified the efficiency of the CasRx endonuclease in the degradation of the eGFP mRNA reporter gene and we established the best conditions for, and the efficient performance of, the CRISPR/CasRx system. The results were measured by fluorescence microscopy, flow cytometry, and qRT-PCR. The analyses demonstrated a reduction in fluorescence, regardless of the amount of eGFP reporter plasmid transfected. The analyses showed an 86–90% reduction in fluorescence by flow cytometry and a 51–80% reduction in mRNA expression by qRT-PCR. Our results demonstrate that the CasRx endonuclease is an efficient tool for eGFP mRNA knockdown. Therefore, subsequent experiments could be useful for the development of a new antiviral tool.


1974 ◽  
Vol 72 (1) ◽  
pp. 111-120 ◽  
Author(s):  
R. Scott ◽  
P. S. Gardner

SUMMARYNasopharyngeal secretions were taken during the acute phase of illness from 66 infants and children admitted to hospital with lower respiratory tract infections. Second secretions were taken, after an interval of 7 days, from 33 of these patients. A significant increase in neutralizing activity to R.S. virus was demonstrated in the nasopharyngeal secretions of patients in response to severe R.S. virus infection. Seventeen out of 25 patients (68%) with R.S. virus infections developed a rise in secretory neutralizing titre, compared with only 1 out of 8 patients (13%) with respiratory infections not involving R.S. virus.A high titre of secretory neutralizing activity was found more often in the acute phase of illness in patients with R.S. virus infections, especially bronchiolitis, than in patients with respiratory infections not involving R.S. virus. Fifteen out of 34 patients (44%) with R.S. virus bronchiolitis were found to possess a neutralizing titre of 1/4 or more in their first secretions, compared with 4 out of 12 patients (33%) with R.S. virus infections other than bronchiolitis and 3 out of 20 patients (15%) with respiratory infections not involving R.S. virus.A quantitative analysis of the immunoglobulins present in the secretions indicated that IgA was the only immunoglobulin consistently present at a detectable concentration. The geometric mean values of IgA, IgM and IgG in the secretions examined were found to be 22·3, 4·3 and 5·3 mg./lOO ml. respectively.The neutralizing activity against R.S. virus, present in the secretions, was shown to be due to specific IgA antibody. This was accomplished by removing the neutralizing activitv in two secretions bv absorotion with anti-IaA serum.


Author(s):  
Montaha Al-Iede ◽  
Lena Sarhan ◽  
Leen Abushanab ◽  
Tamara Ayasrah ◽  
Rafaa Al Maani ◽  
...  

Background: Influenza virus and other respiratory viruses have been identified as an essential cause of acute respiratory infections (ARIs) in children worldwide. However, there are few data on its frequency and clinical presentation in Jordan. Objectives: We aimed to identify the viral etiology of acute respiratory infections and the various clinical presentations in hospitalized children, especially those with influenza viruses compared to other respiratory viruses. Methods: A retrospective study that was conducted at the Jordan university hospital. All the positive nasopharyngeal aspirates that were collected from hospitalized children aged 0-19 years from January 2017 to January 2019 were reviewed. Results: A total of 338 nasopharyngeal aspirates (NPAs) with positive viral serology results were reviewed. Among the patients younger than four years, the RSV virus was the most frequently detected. However, the Influenza B virus was the most commonly seen in patients older than 5 years, H1N1 was more frequent in autumn (29.5%), and RSV was the most frequent virus in winter. Bronchopneumonia was the most frequent diagnosis among all hospitalized patients, followed by bronchiolitis. Out of 338 patients, 50.3 % had tachypnea, 70.7% of patients were admitted to the pediatric floor, while 18.6% presented with a severe illness and required admission to the pediatric intensive care unit (PICU). Infants under the age of one were more likely to have higher co-infection rates with other viruses compared to children over five years that had influenza. Conclusion: Presentations of influenza and other respiratory viruses vary between different age groups, such as sepsis in children younger than one year.


2019 ◽  
Vol 11 (3) ◽  
pp. 38-45
Author(s):  
S. A. Khmilevskaya ◽  
N. I. Zryachkin ◽  
V. E. Mikhailova

The aim: to study the etiological structure of acute respiratory infections in children aged 3 to 12 hospitalized in the early stages of the disease in the department of respiratory infections of the children’s hospital, and to reveal the features of their clinical course and the timing of DNA / RNA elimination of respiratory viruses from nasal secretions, depending on the method of therapy. Materials and methods: 100 children with acute respiratory infections aged 3 to 12 years were monitored. The nasal secrets on the DNA / RNA of respiratory viruses were studied by PCR. Depending on the method of therapy, patients were divided into 2 groups: patients of group 1 (comparison) received basic treatment (without the use of antiviral drugs), in patients of the 2nd group (main), along with basal therapy, the drug was used umifenovir in a 5-day course at the ageappropriate dosage. Results: In the etiologic structure of ARVI in children from 3 to 12 years, the leading place was taken by rhinovirus, influenza and metapneumovirus infections (isolated – 18%, 19% and 20% respectively, in the form of a mixed infection – 11%). The main syndromic diagnosis at the height of the disease was rhinopharyngitis. Complications were observed in 42% of cases, as often as possible with flu – 53% of cases. Features of metapneumovirus infection in children of this age group were: predominance of non-severe forms of the disease in the form of acute fever with symptoms of rhinopharyngitis, as well as a small incidence of lower respiratory tract infections. The use of the drug umiphenovir in children with acute respiratory viral infections of various etiologies contributed to significantly faster elimination of viral DNA / RNA from the nasal secretion, which was accompanied by a ecrease in the duration of the main clinical and hematological symptoms of the disease, a decrease in the incidence of complications, and reduced the duration of stay in hospital. Conclusion: application of modern molecular genetic methods of diagnostics made it possible to identify the leading role of influenza, metapneumovirus and rhinovirus infections in the etiology of acute respiratory viral infection in patients aged 3 to 12 years, and to determine a number of clinical features characteristic of this age group. The results of the study testify to the effectiveness of umiphenovir in the treatment of children with acute respiratory viral infections of various etiologies and allow us to recommend this drug as an effective and safe etiotropic agent.


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