Assessing Differential Binding of Aggregation-Induced Emission-Based Luminogens to Host Interacting Surface Proteins of SARS-CoV-2 and Influenza Virus–An in silico Approach

ABSTRACT The human antibody repertoire has an exceptionally large capacity to recognize new or changing antigens through combinatorial and junctional diversity established at the time of V(D)J recombination and through somatic hypermutation. Influenza viruses exhibit a relentless capacity to escape the human antibody response by altering the amino acids of their surface proteins in hypervariable domains that exhibit a high level of structural plasticity. Both parties in this high-stakes game of shape shifting drive structural evolution of their functional proteins (the B cell receptor/antibody on one side and the viral hemagglutinin and neuraminidase proteins on the other) using error-prone polymerase systems. It is likely that most of the genetic mutations that occur in these systems are deleterious, resulting in the failure of the B cell or virus with mutations to propagate in the immune repertoire or viral quasispecies. A subset of mutations is tolerated in functional surface proteins that enter the B cell or virus progeny pool. In both cases, selection occurs in the population of mutated and unmutated species. In cases where the functional avidity of the B cell receptor is increased significantly, that clone may be selected for preferential expansion. In contrast, an influenza virus that “escapes” the inhibitory effect of secreted antibodies may represent a high proportion of the progeny virus in that host. The recent paper by O’Donnell et al. [C. D. O’Donnell et al., mBio 3(3):e00120-12, 2012] identifies a mechanism for antibody resistance that does not require escape from binding but rather achieves a greater efficiency in replication.

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Structural and Functional Analysis of Surface Proteins from an A(H3N8) Influenza Virus Isolated from New England Harbor Seals

Journal of Virology ◽

10.1128/jvi.02723-14 ◽

2014 ◽

Vol 89 (5) ◽

pp. 2801-2812 ◽

Cited By ~ 11

Author(s):

Hua Yang ◽

Ha T. Nguyen ◽

Paul J. Carney ◽

Zhu Guo ◽

Jessie C. Chang ◽

...

Keyword(s):

Influenza Virus ◽

New England ◽

Receptor Binding ◽

Influenza Virus Infection ◽

Influenza Viruses ◽

Surface Proteins ◽

Harbor Seals ◽

Binding Studies ◽

Binding Preference ◽

Major Surface

ABSTRACTIn late 2011, an A(H3N8) influenza virus infection resulted in the deaths of 162 New England harbor seals. Virus sequence analysis and virus receptor binding studies highlighted potential markers responsible for mammalian adaptation and a mixed receptor binding preference (S. J. Anthony, J. A. St Leger, K. Pugliares, H. S. Ip, J. M. Chan, Z. W. Carpenter, I. Navarrete-Macias, M. Sanchez-Leon, J. T. Saliki, J. Pedersen, W. Karesh, P. Daszak, R. Rabadan, T. Rowles, W. I. Lipkin, MBio 3:e00166-00112, 2012,http://dx.doi.org/10.1128/mBio.00166-12). Here, we present a detailed structural and biochemical analysis of the surface antigens of the virus. Results obtained with recombinant proteins for both the hemagglutinin and neuraminidase indicate a true avian receptor binding preference. Although the detection of this virus in new species highlights an increased potential for cross-species transmission, our results indicate that the A(H3N8) virus currently poses a low risk to humans.IMPORTANCECross-species transmission of zoonotic influenza viruses increases public health concerns. Here, we report a molecular and structural study of the major surface proteins from an A(H3N8) influenza virus isolated from New England harbor seals. The results improve our understanding of these viruses as they evolve and provide important information to aid ongoing risk assessment analyses as these zoonotic influenza viruses continue to circulate and adapt to new hosts.

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Common Features of Coronavirus and Influenza Pandemics and Surface Proteins of their Pathogens. Parallels

Epidemiology and Vaccinal Prevention ◽

10.31631/2073-3046-2021-20-4-4-18 ◽

2021 ◽

Vol 20 (4) ◽

pp. 4-18

Author(s):

E. P. Kharchenko

Keyword(s):

Amino Acids ◽

Influenza Virus ◽

Influenza Viruses ◽

Surface Proteins ◽

S Protein ◽

Common Features ◽

Influenza Pandemics ◽

Intrinsically Disordered Regions ◽

Pandemic Virus ◽

Virus Strains

Relevance. Coronaviruses and influenza viruses induce pandemics taking away many human lives and seeding social-economic chaos. Possibility to prognose pandemic features on characteristics of surface proteins of their pathogens is not investigated.Aim is to characterize the common features of the pandemic coronavirus S-protein and the pandemic virus influenza hemagglutinin in connection with the features of a coronavirus pandemic and influenza pandemics.Materials and method. For the bioinformatic analysis the protein sequences of pandemic coronavirus strains and pandemic influenza virus strains, influenza virus strains of 2017–2018 season and also influenza virus type B strains were used. In proteins an amino acid content, the sums of the charged amino acids and the.Results. It was found out that the increase of amount of the amino acids forming intrinsically disordered regions in the coronavirus S-protein S1 subunit and influenza virus H1 hemagglutinin HA1 subunit is characteristic of the pandemics with high morbidity and the increase of arginine and lysine with comparison with aspartic and glutamic acids in those proteins is peculiar to viruses inducing the pandemics with lower lethality.Conclusion. The features (morbidity and lethality) of the coronavirus pandemic and influenza virus pandemic are associated with the quantitative amino acids content of pandemic virus surface proteins.

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A Study on Host Tropism Determinants of Influenza Virus Using Machine Learning

Current Bioinformatics ◽

10.2174/1574893614666191104160927 ◽

2020 ◽

Vol 15 (2) ◽

pp. 121-134 ◽

Cited By ~ 2

Author(s):

Eunmi Kwon ◽

Myeongji Cho ◽

Hayeon Kim ◽

Hyeon S. Son

Keyword(s):

Machine Learning ◽

Amino Acids ◽

Influenza Virus ◽

Random Forest ◽

Physicochemical Properties ◽

Protein Sequences ◽

Influenza Viruses ◽

Host Tropism ◽

Post Hoc ◽

Ha Protein

Background: The host tropism determinants of influenza virus, which cause changes in the host range and increase the likelihood of interaction with specific hosts, are critical for understanding the infection and propagation of the virus in diverse host species. Methods: Six types of protein sequences of influenza viral strains isolated from three classes of hosts (avian, human, and swine) were obtained. Random forest, naïve Bayes classification, and knearest neighbor algorithms were used for host classification. The Java language was used for sequence analysis programming and identifying host-specific position markers. Results: A machine learning technique was explored to derive the physicochemical properties of amino acids used in host classification and prediction. HA protein was found to play the most important role in determining host tropism of the influenza virus, and the random forest method yielded the highest accuracy in host prediction. Conserved amino acids that exhibited host-specific differences were also selected and verified, and they were found to be useful position markers for host classification. Finally, ANOVA analysis and post-hoc testing revealed that the physicochemical properties of amino acids, comprising protein sequences combined with position markers, differed significantly among hosts. Conclusion: The host tropism determinants and position markers described in this study can be used in related research to classify, identify, and predict the hosts of influenza viruses that are currently susceptible or likely to be infected in the future.

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Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

Scientific Reports ◽

10.1038/s41598-020-79590-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

James D. Allen ◽

Ted M. Ross

Keyword(s):

Influenza Virus ◽

Immune Responses ◽

Influenza A ◽

Seasonal Influenza ◽

Influenza Viruses ◽

Next Generation ◽

Virus Infections ◽

Wild Type ◽

Influenza Hemagglutinin ◽

H3n2 Influenza

AbstractWhile vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.

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Tannic acid-functionalized HEPA filter materials for influenza virus capture

Scientific Reports ◽

10.1038/s41598-020-78929-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Subin Kim ◽

Jinhyo Chung ◽

Sang Hyun Lee ◽

Jeong Hyeon Yoon ◽

Dae-Hyuk Kweon ◽

...

Keyword(s):

Influenza Virus ◽

Tannic Acid ◽

High Efficiency ◽

Influenza Viruses ◽

Capture Efficiency ◽

Protective Equipment ◽

Filter Materials ◽

Washing Process ◽

Pathogenic Viruses ◽

Cost Efficient

AbstractInfluenza, one of the most contagious and infectious diseases, is predominantly transmitted through aerosols, leading to the development of filter-based protective equipment. Though the currently available filters are effective at removing submicron-sized particulates, filter materials with enhanced virus-capture efficiency are still in demand. Coating or chemically modifying filters with molecules capable of binding influenza viruses has received attention as a promising approach for the production of virus-capturing filters. For this purpose, tannic acid (TA), a plant-derived polyphenol, is a promising molecule for filter functionalization because of its antiviral activities and ability to serve as a cost-efficient adhesive for various materials. This study demonstrates the facile preparation of TA-functionalized high-efficiency particulate air (HEPA) filter materials and their efficiency in influenza virus capture. Polypropylene HEPA filter fabrics were coated with TA via a dipping/washing process. The TA-functionalized HEPA filter (TA-HF) exhibits a high in-solution virus capture efficiency of up to 2,723 pfu/mm2 within 10 min, which is almost two orders of magnitude higher than that of non-functionalized filters. This result suggests that the TA-HF is a potent anti-influenza filter that can be used in protective equipment to prevent the spread of pathogenic viruses.

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Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants

Virus Evolution ◽

10.1093/ve/veaa088 ◽

2020 ◽

Vol 6 (2) ◽

Author(s):

B F Koel ◽

R M Vigeveno ◽

M Pater ◽

S M Koekkoek ◽

A X Han ◽

...

Keyword(s):

Neutralizing Antibodies ◽

De Novo ◽

Diagnostic Testing ◽

Influenza Viruses ◽

Surface Proteins ◽

H3n2 Virus ◽

Virus Population ◽

Sample Collection ◽

Routine Surveillance ◽

H3n2 Influenza

Abstract Seasonal human influenza viruses continually change antigenically to escape from neutralizing antibodies. It remains unclear how genetic variation in the intrahost virus population and selection at the level of individual hosts translates to the fast-paced evolution observed at the global level because emerging intrahost antigenic variants are rarely detected. We tracked intrahost variants in the hemagglutinin and neuraminidase surface proteins using longitudinally collected samples from 52 patients infected by A/H3N2 influenza virus, mostly young children, who received oseltamivir treatment. We identified emerging putative antigenic variants and oseltamivir-resistant variants, most of which remained detectable in samples collected at subsequent days, and identified variants that emerged intrahost immediately prior to increases in global rates. In contrast to most putative antigenic variants, oseltamivir-resistant variants rapidly increased to high frequencies in the virus population. Importantly, the majority of putative antigenic variants and oseltamivir-resistant variants were first detectable four or more days after onset of symptoms or start of treatment, respectively. Our observations demonstrate that de novo variants emerge, and may be positively selected, during the course of infection. Additionally, based on the 4–7 days post-treatment delay in emergence of oseltamivir-resistant variants in six out of the eight individuals with such variants, we find that limiting sample collection for routine surveillance and diagnostic testing to early timepoints after onset of symptoms can potentially preclude detection of emerging, positively selected variants.

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Sequential Seasonal H1N1 Influenza Virus Infections Protect Ferrets against Novel 2009 H1N1 Influenza Virus

Journal of Virology ◽

10.1128/jvi.02257-12 ◽

2012 ◽

Vol 87 (3) ◽

pp. 1400-1410 ◽

Cited By ~ 45

Author(s):

Donald M. Carter ◽

Chalise E. Bloom ◽

Eduardo J. M. Nascimento ◽

Ernesto T. A. Marques ◽

Jodi K. Craigo ◽

...

Keyword(s):

Influenza Virus ◽

H1n1 Influenza ◽

Cross Reactivity ◽

Influenza Viruses ◽

The Novel ◽

Virus Infections ◽

H1n1 Influenza Virus ◽

Virus Shedding ◽

2009 H1n1 ◽

Novel H1n1 Influenza

ABSTRACTIndividuals <60 years of age had the lowest incidence of infection, with ∼25% of these people having preexisting, cross-reactive antibodies to novel 2009 H1N1 influenza. Many people >60 years old also had preexisting antibodies to novel H1N1. These observations are puzzling because the seasonal H1N1 viruses circulating during the last 60 years were not antigenically similar to novel H1N1. We therefore hypothesized that a sequence of exposures to antigenically different seasonal H1N1 viruses can elicit an antibody response that protects against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains. These results were compared to those of ferrets that were sequentially infected with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses. Following seroconversion, ferrets were challenged with novel H1N1 influenza virus and assessed for viral titers in the nasal wash, morbidity, and mortality. There was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected with any single seasonal H1N1 influenza viruses, with limited protection to challenge. However, sequential H1N1 influenza infections reduced the incidence of disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount and duration of virus shedding and the frequency of transmission following novel H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza viruses, and not to any single H1N1 influenza virus, elicits a breadth of antibodies that neutralize novel H1N1 even though the host was never exposed to the novel H1N1 influenza viruses.

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

Viruses ◽

10.3390/v13020234 ◽

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.

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The efficacy of live and inactivated vaccines of Hong Kong influenza virus in an industrial community: A report to the Medical Research Council Committee on Influenza and other respiratory virus vaccines

Epidemiology and Infection ◽

10.1017/s0022172400022907 ◽

1973 ◽

Vol 71 (4) ◽

pp. 641-647 ◽

Cited By ~ 14

Author(s):

D. Hobson ◽

F. A. Baker ◽

R. L. Curry ◽

A. S. Beare ◽

P. M. O. Massey

Keyword(s):

Influenza Virus ◽

Hong Kong ◽

Medical Research ◽

Research Council ◽

Respiratory Virus ◽

Medical Research Council ◽

Influenza Viruses ◽

Protective Efficiency ◽

Industrial Community ◽

Inactivated Vaccines

Intranasal vaccines of inactivated or living attentuated A2/Hong Kong influenza viruses were compared for clinical acceptability, serological effects and protective efficiency against natural epidemic influenza in a large industrial and clerical population.

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