scholarly journals Synthesis and Biological Evaluation of Novel (thio)semicarbazone-Based Benzimidazoles as Antiviral Agents against Human Respiratory Viruses

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1487 ◽  
Author(s):  
Valeria Francesconi ◽  
Elena Cichero ◽  
Silvia Schenone ◽  
Lieve Naesens ◽  
Michele Tonelli
Keyword(s):  
Influenza A ◽  
Antiviral Agents ◽  
Binding Mode ◽  
Respiratory Viruses ◽  
Biological Evaluation ◽  
Benzimidazole Derivatives ◽  
Respiratory Illnesses ◽  
Medical Need ◽  
Dual Inhibitors ◽  
Syncytial Virus

Respiratory RNA viruses are responsible for recurrent acute respiratory illnesses that still represent a major medical need. Previously we developed a large variety of benzimidazole derivatives able to inhibit these viruses. Herein, two series of (thio)semicarbazone- and hydrazone-based benzimidazoles have been explored, by derivatizing 5-acetyl benzimidazoles previously reported by us, thereby evaluating the influence of the modification on the antiviral activity. Compounds 6, 8, 16 and 17, bearing the 5-(thio)semicarbazone and 5-hydrazone functionalities in combination with the 2-benzyl ring on the benzimidazole core structure, acted as dual inhibitors of influenza A virus and human coronavirus. For respiratory syncytial virus (RSV), activity is limited to the 5-thiosemicarbazone (25) and 5-hydrazone (22) compounds carrying the 2-[(benzotriazol-1/2-yl)methyl]benzimidazole scaffold. These molecules proved to be the most effective antiviral agents, able to reach the potency profile of the licensed drug ribavirin. The molecular docking analysis explained the SAR of these compounds around their binding mode to the target RSV F protein, revealing the key contacts for further assessment. The herein-investigated benzimidazole-based derivatives may represent valuable hit compounds, deserving subsequent structural improvements towards more efficient antiviral agents for the treatment of pathologies caused by these human respiratory viruses.

scholarly journals Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 234
Author(s):  
Sarah Al-Beltagi ◽  
Cristian Alexandru Preda ◽  
Leah V. Goulding ◽  
Joe James ◽  
Juan Pu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Virus Challenge ◽  
2009 H1n1 ◽  
Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

scholarly journals Rapid disappearance of influenza following the implementation of COVID-19 mitigation measures in Hamilton, Ontario

2021 ◽  
Vol 47 (04) ◽  
pp. 202-208
Author(s):  
Kevin Zhang ◽  
Avika Misra ◽  
Patrick J Kim ◽  
Seyed M Moghadas ◽  
Joanne M Langley ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza A ◽  
Respiratory Virus ◽  
Respiratory Viruses ◽  
Mitigation Measures ◽  
Nasopharyngeal Swab ◽  
Health Measures ◽  
Bayesian Linear Regression ◽  
Syncytial Virus ◽  
The Impact

Background: Public health measures, such as physical distancing and closure of schools and non-essential services, were rapidly implemented in Canada to interrupt the spread of the coronavirus disease 2019 (COVID-19). We sought to investigate the impact of mitigation measures during the spring wave of COVID-19 on the incidence of other laboratory-confirmed respiratory viruses in Hamilton, Ontario. Methods: All nasopharyngeal swab specimens (n=57,503) submitted for routine respiratory virus testing at a regional laboratory serving all acute-care hospitals in Hamilton between January 2010 and June 2020 were reviewed. Testing for influenza A and B, respiratory syncytial virus, human metapneumovirus, parainfluenza I–III, adenovirus, and rhinovirus/enterovirus was done routinely using a laboratory-developed polymerase chain reaction multiplex respiratory viral panel. A Bayesian linear regression model was used to determine the trend of positivity rates of all influenza samples for the first 26 weeks of each year from 2010 to 2019. The mean positivity rate of Bayesian inference was compared with the weekly reported positivity rate of influenza samples in 2020. Results: The positivity rate of influenza in 2020 diminished sharply following the population-wide implementation of COVID-19 interventions. Weeks 12–26 reported 0% positivity for influenza, with the exception of 0.1% reported in week 13. Conclusion: Public health measures implemented during the COVID-19 pandemic were associated with a reduced incidence of other respiratory viruses and should be considered to mitigate severe seasonal influenza and other respiratory virus pandemics.

scholarly journals Circulation of Respiratory Viruses in Hospitalized Adults before and during the COVID-19 Pandemic in Brescia, Italy: A Retrospective Study

2021 ◽  
Vol 18 (18) ◽  
pp. 9525
Author(s):  
Maria Antonia De Francesco ◽  
Caterina Pollara ◽  
Franco Gargiulo ◽  
Mauro Giacomelli ◽  
Arnaldo Caruso
Keyword(s):  
Respiratory Syncytial Virus ◽  
Influenza A ◽  
Statistical Significance ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Contact Tracing ◽  
Nucleic Acid Detection ◽  
Respiratory Pathogens ◽  
Syncytial Virus ◽  
Human Coronaviruses

Different preventive public health measures were adopted globally to limit the spread of SARS-CoV-2, such as hand hygiene and the use of masks, travel restrictions, social distance actions such as the closure of schools and workplaces, case and contact tracing, quarantine and lockdown. These measures, in particular physical distancing and the use of masks, might have contributed to containing the spread of other respiratory viruses that occurs principally by contact and droplet routes. The aim of this study was to evaluate the prevalence of different respiratory viruses (influenza viruses A and B, respiratory syncytial virus, parainfluenza viruses 1, 2, 3 and 4, rhinovirus, adenovirus, metapneumovirus and human coronaviruses) after one year of the pandemic. Furthermore, another aim was to evaluate the possible impact of these non-pharmaceutical measures on the circulation of seasonal respiratory viruses. This single center study was conducted between January 2017–February 2020 (pre-pandemic period) and March 2020–May 2021 (pandemic period). All adults >18 years with respiratory symptoms and tested for respiratory pathogens were included in the study. Nucleic acid detection of all respiratory viruses was performed by multiplex real time PCR. Our results show that the test positivity for influenza A and B, metapneumovirus, parainfluenza virus, respiratory syncytial virus and human coronaviruses decreased with statistical significance during the pandemic. Contrary to this, for adenovirus the decrease was not statistically significant. Conversely, a statistically significant increase was detected for rhinovirus. Coinfections between different respiratory viruses were observed during the pre-pandemic period, while the only coinfection detected during pandemic was between SARS-CoV-2 and rhinovirus. To understand how the preventive strategies against SARS-CoV-2 might alter the transmission dynamics and epidemic patterns of respiratory viruses is fundamental to guide future preventive recommendations.

scholarly journals Influenza and RSV incidence during COVID-19 pandemic—an observational study from in-hospital point-of-care testing

2021 ◽  
Author(s):  
Paul Stamm ◽  
Ingo Sagoschen ◽  
Kerstin Weise ◽  
Bodo Plachter ◽  
Thomas Münzel ◽  
...  
Keyword(s):  
Emergency Room ◽  
Influenza A ◽  
Point Of Care ◽  
Respiratory Viruses ◽  
Pediatric Emergency ◽  
Influenza B ◽  
Complete Suppression ◽  
Emergency Room Patients ◽  
Syncytial Virus ◽  
Point Of Care Tests

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has forced the implementation of unprecedented public health measures strategies which might also have a significant impact on the spreading of other viral pathogens such as influenza and Respiratory Syncytial Virus (RSV) . The present study compares the incidences of the most relevant respiratory viruses before and during the SARS-CoV-2 pandemic in emergency room patients. We analyzed the results of in total 14,946 polymerase chain reaction point-of-care tests (POCT-PCR) for Influenza A, Influenza B, RSV and SARS-CoV-2 in an adult and a pediatric emergency room between December 1, 2018 and March 31, 2021. Despite a fivefold increase in the number of tests performed, the positivity rate for Influenza A dropped from 19.32% (165 positives of 854 tests in 2018/19), 14.57% (149 positives of 1023 in 2019–20) to 0% (0 positives of 4915 tests) in 2020/21. In analogy, the positivity rate for Influenza B and RSV dropped from 0.35 to 1.47%, respectively, 10.65–21.08% to 0% for both in 2020/21. The positivity rate for SARS-CoV2 reached 9.74% (110 of 1129 tests performed) during the so-called second wave in December 2020. Compared to the two previous years, seasonal influenza and RSV incidence was eliminated during the COVID-19 pandemic. Corona-related measures and human behavior patterns could lead to a significant decline or even complete suppression of other respiratory viruses such as influenza and RSV.

scholarly journals Comparison of detection rate of 16 sampling methods for respiratory viruses: a Bayesian network meta-analysis of clinical data and systematic review

2020 ◽  
Vol 5 (11) ◽  
pp. e003053
Author(s):  
Nianzong Hou ◽  
Kai Wang ◽  
Haiyang Zhang ◽  
Mingjian Bai ◽  
Hao Chen ◽  
...  
Keyword(s):  
Influenza A ◽  
Detection Rate ◽  
Sampling Methods ◽  
Meta Analysis ◽  
Random Effect ◽  
Splitting Method ◽  
Respiratory Viruses ◽  
Nasopharyngeal Swab ◽  
Specific Virus ◽  
Syncytial Virus

BackgroundRespiratory viruses (RVs) is a common cause of illness in people of all ages, at present, different types of sampling methods are available for respiratory viral diagnosis. However, the diversity of available sampling methods and the limited direct comparisons in randomised controlled trials (RCTs) make decision-making difficult. We did a network meta-analysis, which accounted for both direct and indirect comparisons, to determine the detection rate of different sampling methods for RVs.MethodsRelevant articles were retrieved comprehensively by searching the online databases of PubMed, Embase and Cochrane published before 25 March 2020. With the help of R V.3.6.3 software and ‘GeMTC V.0.8.2’ package, network meta-analysis was performed within a Bayesian framework. Node-splitting method and I2 test combined leverage graphs and Gelman-Rubin-Brooks plots were conducted to evaluate the model’s accuracy. The rank probabilities in direct and cumulative rank plots were also incorporated to rank the corresponding sampling methods for overall and specific virus.Results16 sampling methods with 54 438 samples from 57 literatures were ultimately involved in this study. The model indicated good consistency and convergence but high heterogeneity, hence, random-effect analysis was applied. The top three sampling methods for RVs were nasopharyngeal wash (NPW), mid-turbinate swab (MTS) and nasopharyngeal swab (NPS). Despite certain differences, the results of virus-specific subanalysis were basically consistent with RVs: MTS, NPW and NPS for influenza; MTS, NPS and NPW for influenza-a and b; saliva, NPW and NPS for rhinovirus and parainfluenza; NPW, MTS and nasopharyngeal aspirate for respiratory syncytial virus; saliva, NPW and MTS for adenovirus and sputum; MTS and NPS for coronavirus.ConclusionThis network meta-analysis provides supporting evidences that NPW, MTS and NPS have higher diagnostic value regarding RVs infection, moreover, particular preferred methods should be considered in terms of specific virus pandemic. Of course, subsequent RCTs with larger samples are required to validate our findings.

scholarly journals Metagenomic Sequencing To Detect Respiratory Viruses in Persons under Investigation for COVID-19

2020 ◽  
Vol 59 (1) ◽  
pp. e02142-20
Author(s):  
Ahmed Babiker ◽  
Heath L. Bradley ◽  
Victoria D. Stittleburg ◽  
Jessica M. Ingersoll ◽  
Autum Key ◽  
...  
Keyword(s):  
Influenza A ◽  
Viral Infections ◽  
Respiratory Viruses ◽  
Human Metapneumovirus ◽  
Molecular Testing ◽  
Metagenomic Sequencing ◽  
Rt Pcr ◽  
Human Coronavirus ◽  
Testing Algorithms ◽  
Syncytial Virus

ABSTRACTBroad testing for respiratory viruses among persons under investigation (PUIs) for SARS-CoV-2 has been performed inconsistently, limiting our understanding of alternative viral infections and coinfections in these patients. RNA metagenomic next-generation sequencing (mNGS) offers an agnostic tool for the detection of both SARS-CoV-2 and other RNA respiratory viruses in PUIs. Here, we used RNA mNGS to assess the frequencies of alternative viral infections in SARS-CoV-2 RT-PCR-negative PUIs (n = 30) and viral coinfections in SARS-CoV-2 RT-PCR-positive PUIs (n = 45). mNGS identified all viruses detected by routine clinical testing (influenza A [n = 3], human metapneumovirus [n = 2], and human coronavirus OC43 [n = 2], and human coronavirus HKU1 [n = 1]). mNGS also identified both coinfections (1, 2.2%) and alternative viral infections (4, 13.3%) that were not detected by routine clinical workup (respiratory syncytial virus [n = 3], human metapneumovirus [n = 1], and human coronavirus NL63 [n = 1]). Among SARS-CoV-2 RT-PCR-positive PUIs, lower cycle threshold (CT) values correlated with greater SARS-CoV-2 read recovery by mNGS (R2, 0.65; P < 0.001). Our results suggest that current broad-spectrum molecular testing algorithms identify most respiratory viral infections among SARS-CoV-2 PUIs, when available and implemented consistently.

scholarly journals New polycyclic dual inhibitors of the wild type and the V27A mutant M2 channel of the influenza A virus with unexpected binding mode

2015 ◽  
Vol 96 ◽  
pp. 318-329 ◽  
Author(s):  
Matias Rey-Carrizo ◽  
Sabrina Gazzarrini ◽  
Salomé Llabrés ◽  
Marta Frigolé-Vivas ◽  
Jordi Juárez-Jiménez ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Binding Mode ◽  
Wild Type ◽  
Dual Inhibitors

scholarly journals A Throat Lozenge Containing Amyl Meta Cresol and Dichlorobenzyl Alcohol Has a Direct Virucidal Effect on Respiratory Syncytial Virus, Influenza a and SARS-CoV

2005 ◽  
Vol 16 (2) ◽  
pp. 129-134 ◽  
Author(s):  
John S Oxford ◽  
Robert Lambkin ◽  
Iain Gibb ◽  
Shobana Balasingam ◽  
Charlotte Chan ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Influenza A ◽  
Morphological Changes ◽  
Respiratory Viruses ◽  
Low Ph ◽  
Icosahedral Symmetry ◽  
Viral Membrane ◽  
Virucidal Effect ◽  
Syncytial Virus ◽  
Virus Influenza

A potent virucidal mixture containing amyl metacresol and dichlorobenzyl alcohol at low pH inactivated enveloped respiratory viruses influenza A, respiratory synctial virus (RSV) and severe acute respiratory syndrome coronavirus (SARS-CoV) but not viruses with icosahedral symmetry, such as adenoviruses or rhinoviruses. A titre of approximately 3.5 log10 TCID50 was reduced to below the level of detection within two minutes. Electron microscopy of purified influenza A virus showed extensive clumping and morphological changes in spike configuration after contact with the virucidal mixture, but no overt destruction of the viral membrane. We conclude that, formulated as a lozenge, the mixture could have significant effects in reducing the infectivity of certain infectious viruses in the throat and presumably in cough droplets, thus reducing, theoretically, opportunities for person-to-person transmission.

scholarly journals Respiratory Viral Pathogens in Children Evaluated at Military Treatment Facilities in Oahu, Hawaii From 2014 to 2018: Seasonality and Climatic Factors

2020 ◽  
Author(s):  
Agnes S Montgomery ◽  
Michael B Lustik ◽  
Milissa U Jones ◽  
Timothy S Horseman
Keyword(s):  
Respiratory Syncytial Virus ◽  
Influenza A ◽  
Climatic Factors ◽  
Medical Center ◽  
Respiratory Viruses ◽  
Preventive Strategies ◽  
Viral Pathogens ◽  
Treatment Facilities ◽  
Syncytial Virus ◽  
Military Treatment Facilities

Abstract Five-year retrospective analysis of respiratory viruses in children less than 18 years old at Tripler Army Medical Center and outlying clinics in Oahu. Respiratory syncytial virus and influenza A showed pronounced seasonality with peaks from September to December and December to March, respectively. Results provide a better understanding of the timing of viral preventive strategies in Oahu.

scholarly journals Nasopharyngeal density of respiratory viruses in childhood pneumonia in a highly vaccinated setting: findings from a case–control study

2020 ◽  
Vol 7 (1) ◽  
pp. e000593
Author(s):  
Mejbah Uddin Bhuiyan ◽  
Tom Snelling ◽  
Chisha Sikazwe ◽  
Jurissa Lang ◽  
Meredith Borland ◽  
...  
Keyword(s):  
Influenza A ◽  
Operating Characteristic ◽  
Linear Regression Analysis ◽  
Disease Status ◽  
Respiratory Viruses ◽  
Case Control ◽  
Asymptomatic Children ◽  
Syncytial Virus ◽  
Actual Contribution ◽  
Control Study

BackgroundDetection of pneumonia-causing respiratory viruses in the nasopharynx of asymptomatic children has made their actual contribution to pneumonia unclear. We compared nasopharyngeal viral density between children with and without pneumonia to understand if viral density could be used to diagnose pneumonia.MethodsNasopharyngeal swabs (NPS) were collected from hospitalised pneumonia cases at Princess Margaret Hospital (PMH) and contemporaneous age-matched controls at PMH outpatient clinics and a local immunisation clinic in Perth, Australia. The density (copies/mL) of respiratory syncytial virus (RSV), influenza A virus (InfA), human metapneumovirus (HMPV) and rhinovirus in NPS was determined using quantitative PCR. Linear regression analysis was done to assess the trend between viral density and age in months. The association between viral density and disease status was examined using logistic regression. Area under receiver operating characteristic (AUROC) curves were assessed to determine optimal discriminatory viral density cut-offs.ResultsThrough May 2015 to October 2017, 230 pneumonia cases and 230 controls were enrolled. Median nasopharyngeal density for any respiratory virus was not substantially higher in cases than controls (p>0.05 for each). A decreasing density trend with increasing age was observed—the trend was statistically significant for RSV (regression coefficient −0.04, p=0.004) but not for other viruses. After adjusting for demographics and other viral densities, for every log10 copies/mL density increase, the odds of being a case increased by six times for RSV, three times for HMPV and two times for InfA. The AUROC curves were <0.70 for each virus, suggesting poor case–control discrimination based on viral density.ConclusionThe nasopharyngeal density of respiratory viruses was not significantly higher in children with pneumonia than those without; however, the odds of being a case increased with increased density for some viruses. The utility of viral density, alone, in defining pneumonia was limited.

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