scholarly journals Identification of Novel Influenza Polymerase PB2 Inhibitors Using a Cascade Docking Virtual Screening Approach

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5291
Author(s):  
Lei Zhao ◽  
Jinjing Che ◽  
Qian Zhang ◽  
Yiming Li ◽  
Xiaojia Guo ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Resistant Strain ◽  
Influenza A ◽  
Influenza B ◽  
Molecular Weights ◽  
Lead Compounds ◽  
Compound Libraries ◽  
Kd Values ◽  
Virtual Screening Approach ◽  
Influenza Polymerase

To discover novel inhibitors that target the influenza polymerase basic protein 2 (PB2) cap-binding domain (CBD), commercial ChemBridge compound libraries containing 384,796 compounds were screened using a cascade docking of LibDock–LigandFit–GOLD, and 60 compounds were selected for testing with cytopathic effect (CPE) inhibition assays and surface plasmon resonance (SPR) assay. Ten compounds were identified to rescue cells from H1N1 virus-mediated death at non-cytotoxic concentrations with EC50 values ranging from 0.30 to 67.65 μM and could bind to the PB2 CBD of H1N1 with Kd values ranging from 0.21 to 6.77 μM. Among these, four compounds (11D4, 12C5, 21A5, and 21B1) showed inhibition of a broad spectrum of influenza virus strains, including oseltamivir-resistant ones, the PR/8-R292K mutant (H1N1, recombinant oseltamivir-resistant strain), the PR/8-I38T mutant (H1N1, recombinant baloxavir-resistant strain), and the influenza B/Lee/40 virus strain. These compounds have novel chemical scaffolds and relatively small molecular weights and are suitable for optimization as lead compounds. Based on sequence and structure comparisons of PB2 CBDs of various influenza virus subtypes, we propose that the Phe323/Gln325, Asn429/Ser431, and Arg355/Gly357 mutations, particularly the Arg355/Gly357 mutation, have a marked impact on the selectivities of PB2 CBD-targeted inhibitors of influenza A and influenza B.

scholarly journals Inhibitory effects of aprotinin on influenza A and B viruses in vitro and in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eun-Jung Song ◽  
Erica Españo ◽  
Sang-Mu Shim ◽  
Jeong-Hyun Nam ◽  
Jiyeon Kim ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Lethal Dose ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Inhibitory Effects ◽  
Compound Libraries ◽  
Wide Range

AbstractInfluenza viruses cause significant morbidity and mortality worldwide. Long-term or frequent use of approved anti-influenza agents has resulted in drug-resistant strains, thereby necessitating the discovery of new drugs. In this study, we found aprotinin, a serine protease inhibitor, as an anti-influenza candidate through screening of compound libraries. Aprotinin has been previously reported to show inhibitory effects on a few influenza A virus (IAV) subtypes (e.g., seasonal H1N1 and H3N2). However, because there were no reports of its inhibitory effects on the other types of influenza viruses, we investigated the inhibitory effects of aprotinin in vitro on a wide range of influenza viruses, including avian and oseltamivir-resistant influenza virus strains. Our cell-based assay showed that aprotinin had inhibitory effects on seasonal human IAVs (H1N1 and H3N2 subtypes), avian IAVs (H5N2, H6N5, and H9N2 subtypes), an oseltamivir-resistant IAV, and a currently circulating influenza B virus. We have also confirmed its activity in mice infected with a lethal dose of influenza virus, showing a significant increase in survival rate. Our findings suggest that aprotinin has the capacity to inhibit a wide range of influenza virus subtypes and should be considered for development as a therapeutic agent against influenza.

scholarly journals Influenza: An Emerging and Re-emerging Public Health Threat in Nepal

2018 ◽  
Vol 3 (2) ◽  
pp. 1-2
Author(s):  
Bishnu Prasad Upadhyay
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Winter Season ◽  
Emerging Infectious Diseases ◽  
Influenza Viruses ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Influenza A H1n1 ◽  
New Variant ◽  
Seasonal Epidemics

Influenza virus type A and B are responsible for seasonal epidemics as well as pandemics in human. Influenza A viruses are further divided into two major groups namely, low pathogenic seasonal influenza (A/H1N1, A/H1N1 pdm09, A/H3N2) and highly pathogenic influenza virus (H5N1, H5N6, H7N9) on the basis of two surface antigens: hemagglutinin (HA) and neuraminidase (NA). Mutations, including substitutions, deletions, and insertions, are one of the most important mechanisms for producing new variant of influenza viruses. During the last 30 years; more than 50 viral threat has been evolved in South-East Asian countriesof them influenza is one of the major emerging and re-emerging infectious diseases of global concern. Similar to tropical and sub-tropical countries of Southeast Asia; circulation of A/H1N1 pdm09, A/H3N2 and influenza B has been circulating throughout the year with the peak during July-November in Nepal. However; the rate of infection transmission reach peak during the post-rain and winter season of Nepal.

Severe Influenza Virus Infection in Children Admitted to the PICU: Comparison of Influenza A and Influenza B Virus Infection

2021 ◽  
Author(s):  
Pınar YAZICI ÖZKAYA ◽  
Eşe Eda TURANLI ◽  
Hamdi METİN ◽  
Ayça Aydın UYSAL ◽  
Candan ÇİÇEK ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza B Virus ◽  
Influenza B ◽  
Severe Influenza ◽  
B Virus

scholarly journals Haemagglutination-inhibition antibodies against influenza A and influenza B in maternal and neonatal sera

1978 ◽  
Vol 80 (1) ◽  
pp. 13-19 ◽  
Author(s):  
N. Masurel ◽  
J. I. de Bruijne ◽  
H. A. Beuningh ◽  
H. J. A. Schouten
Keyword(s):  
Influenza Virus ◽  
Maternal Age ◽  
Influenza A ◽  
Haemagglutination Inhibition ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
Duration Of Pregnancy ◽  
Pregnancy And Birth

SUMMARYHaemagglutination inhibition (HI) antibodies against the influenza viruses A/Hong Kong/8/68 (H3N2) and B/Nederland/77/66 were determined in 420 paired sera from mothers and newborns (umbilical cord sera), sampled in 1970–1.A higher concentration of antibodies against influenza A virus was found more frequently in neonatal than in maternal sera. By contrast, low titres against influenza B virus were more frequently observed in neonatal than in maternal sera. Maternal age, duration of pregnancy, and birth-weight did not affect the results of the tests.It is suggested that the titre of the newborn against an epidemic influenza virus can be predicted from that of the mother. Furthermore, the maternal titre may be an indication of the susceptibility of the newborn infant to influenza infections.

scholarly journals Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Mira C. Patel ◽  
Kari Ann Shirey ◽  
Marina S. Boukhvalova ◽  
Stefanie N. Vogel ◽  
Jorge C. G. Blanco
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
High Mobility ◽  
Influenza B Virus ◽  
Influenza B ◽  
Lung Pathology ◽  
B Virus ◽  
Cotton Rats

ABSTRACT Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI. IMPORTANCE Influenza virus is a common infectious agent causing serious seasonal epidemics, and there is urgent need to develop an alternative treatment modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI.

scholarly journals Performance of the Molecular Alere i Influenza A&B Test Compared to That of the Xpert Flu A/B Assay

2014 ◽  
Vol 53 (2) ◽  
pp. 706-709 ◽  
Author(s):  
Kimberle C. Chapin ◽  
Estefany J. Flores-Cortez
Keyword(s):  
Influenza Virus ◽  
Sensitivity And Specificity ◽  
Influenza A ◽  
Point Of Care ◽  
Type A ◽  
Influenza B ◽  
Clinical Sensitivity ◽  
Transport Medium ◽  
The Poor ◽  
B Test

Data on the performance of rapid molecular point-of-care use platforms for diagnosis of influenza are lacking. We validated nasopharyngeal (NP) flocked specimens in universal transport medium (UTM) and evaluated the clinical sensitivity and specificity of the Alere i influenza A&B test compared to those of the Xpert flu A/B assay. The Alere i influenza A&B test had an overall sensitivity and specificity of 93.8% and 62.5% for influenza A, respectively, and of 91.8% and 53.6% for influenza B, respectively. The poor specificity was due to influenza virus samples determined positive for both type A and B.

scholarly journals Detection of severe acute respiratory syndrome coronavirus 2 and influenza viruses based on CRISPR-Cas12a

2020 ◽  
pp. 153537022096379
Author(s):  
Oraphan Mayuramart ◽  
Pattaraporn Nimsamer ◽  
Somruthai Rattanaburi ◽  
Naphat Chantaravisoot ◽  
Kritsada Khongnomnan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Severe Acute Respiratory Syndrome ◽  
Influenza A ◽  
Limit Of Detection ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Influenza Virus A ◽  
B Virus

Due to the common symptoms of COVID-19, patients are similar to influenza-like illness. Therefore, the detection method would be crucial to discriminate between SARS-CoV-2 and influenza virus-infected patients. In this study, CRISPR-Cas12a-based detection was applied for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus which would be a practical and attractive application for screening of patients with COVID-19 and influenza in areas with limited resources. The limit of detection for SARS-CoV-2, influenza A, and influenza B detection was 10, 103, and 103 copies/reaction, respectively. Moreover, the assays yielded no cross-reactivity against other respiratory viruses. The results revealed that the detection of influenza virus and SARS-CoV-2 by using RT-RPA and CRISPR-Cas12a technology reaches 96.23% sensitivity and 100% specificity for SARS-CoV-2 detection. The sensitivity for influenza virus A and B detections was 85.07% and 94.87%, respectively. In addition, the specificity for influenza virus A and B detections was approximately 96%. In conclusion, the RT-RPA with CRISPR-Cas12a assay was an effective method for the screening of influenza viruses and SARS-CoV-2 which could be applied to detect other infectious diseases in the future.

Dual and Triple Infections With Influenza A and B Viruses: A Case-Control Study in Southern Brazil

2019 ◽  
Vol 220 (6) ◽  
pp. 961-968 ◽  
Author(s):  
Tatiana Schäffer Gregianini ◽  
Ivana R Santos Varella ◽  
Patricia Fisch ◽  
Letícia Garay Martins ◽  
Ana B G Veiga
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Clinical Symptoms ◽  
Antiviral Treatment ◽  
Influenza Virus Infection ◽  
H3n2 Virus ◽  
Influenza Surveillance ◽  
Influenza B Virus ◽  
Influenza B ◽  
Influenza A H1n1

Abstract Influenza surveillance is important for disease control and should consider possible coinfection with different viruses, which can be associated with disease severity. This study analyzed 34 459 patients with respiratory infection from 2009 to 2018, of whom 8011 were positive for influenza A virus (IAV) or influenza B virus (IBV). We found 18 cases of dual influenza virus infection, including coinfection with 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) and influenza A(H3N2) virus (1 case), A(H1N1)pdm09 and IBV (6 cases), A(H3N2) and IBV (8 cases), and nonsubtyped IAV and IBV (3 cases); and 1 case of triple infection with A(H3N2), A(H1N1)pdm09, and IBV. Compared with 76 monoinfected patients, coinfection was significantly associated with cardiopathy and death. Besides demographic characteristics and clinical symptoms, we assessed vaccination status, antiviral treatment, timeliness of antiviral use, hospitalization, and intensive care unit admission, but no significant differences were found between coinfected and monoinfected cases. Our findings indicate that influenza virus coinfection occurs more often than previously reported and that it can lead to a worse disease outcome.

scholarly journals Occurrence of influenza B/Hong Kong-Like strains in Brazil, during 2002

2003 ◽  
Vol 45 (1) ◽  
pp. 51-52 ◽  
Author(s):  
Terezinha Maria de Paiva ◽  
Maria Akiko Ishida ◽  
Maria Gisele Gonçalves ◽  
Margareth Aparecida Benega ◽  
Maria Candida Oliveira de Souza ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Influenza A ◽  
Vaccination Campaign ◽  
Age Groups ◽  
Respiratory Illness ◽  
The Elderly ◽  
Influenza B ◽  
Surveillance Period ◽  
Influenza A H1n1

Through the influenza virus surveillance from January to October 2002, influenza B/Hong Kong-like strains circulating in the Southeast and Centre East regions of Brazil have been demonstrated. This strain is a variant from B/Victoria/02/88 whose since 1991 and until recently have been isolated relatively infrequently and have been limited to South-Eastern Asia. A total of 510 respiratory secretions were collected from patients 0 to 60 years of age, with acute respiratory illness, living in the Southeast and Centre East regions of Brazil, of which 86 (17.13%) were positive for influenza virus. Among them 12 (13.95%) were characterized as B/Hong Kong/330/2001; 3 (3.49%) as B/Hong Kong/1351/2002 a variant from B/Hong Kong/330/2001; 1 (1.16%) as B/Sichuan/379/99; 1 (1.16%) as B/Shizuoka/5/2001, until now. The percentages of cases notified during the surveillance period were 34.88%, 15.12%, 15.12%, 4.65%, 15.12%, 13.95%, in the age groups of 0-4, 5-10, 11-15, 16-20, 21-30, 31-50, respectively. The highest proportion of isolates was observed among children younger than 4 years but serious morbidity and mortality has not been observed among people older than 65 years, although B influenza virus component for vaccination campaign 2002 was B/Sichuan/379/99 strain. This was probably due to the elderly protection acquired against B/Victoria/02/88. In addition, in influenza A/Panama/2007/99-like (H3N2) strains 22 (25.58%) were also detected, but influenza A(H1N1) has not been detected yet.

scholarly journals Molecular Epidemiology and Antigenic Characterization of Seasonal Influenza Viruses Circulating in Nepal

2017 ◽  
Vol 15 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Bishu Prasad Upadhyay ◽  
Prakash Ghimire ◽  
Masato Tashiro ◽  
Mogha Raj Banjara
Keyword(s):  
New York ◽  
Influenza Virus ◽  
Molecular Epidemiology ◽  
Influenza A ◽  
Influenza Viruses ◽  
Influenza B ◽  
Antigenic Characterization ◽  
Geographical Regions ◽  
Influenza A H1n1 ◽  
Health Burdens

Background: Influenza is one of the public health burdens in Nepal and its epidemiology is not clearly understood. The objective of this study was to explore the molecular epidemiology and the antigenic characteristics of the circulating influenza viruses in Nepal.Methods: A total of 1495 throat swab specimens were collected from January to December, 2014. Real time PCR assay was used for identification of influenza virus types and subtypes. Ten percent of the positive specimens were randomly selected and inoculated onto Madin-Darby Canine Kidney Epithelial cells (MDCK) for influenza virus isolation. All viruses were characterized by the hemagglutination inhibition (HI) assay.Results: Influenza viruses were detected in 421/1495 (28.2%) specimens. Among positive cases, influenza A virus was detected in 301/421 (71.5%); of which 120 (39.9%) were influenza A/H1N1 pdm09 and 181 (60.1%) were influenza A/H3 subtype. Influenza B viruses were detected in 119/421 (28.3%) specimens. Influenza A/H1N1 pdm09, A/H3 and B viruses isolated in Nepal were antigenically similar to the vaccine strain influenza A/California/07/2009(H1N1pdm09), A/Texas/50/2012(H3N2), A/New York/39/2012(H3N2) and B/Massachusetts/2/2012, respectively.Conclusions: Influenza viruses were reported year-round in different geographical regions of Nepal which was similar to other tropical countries. The circulating influenza virus type and subtypes of Nepal were similar to vaccine candidate virus which could be prevented by currently used influenza vaccine.

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