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  1. Article ; Online: A Perspective on Studies of Phage DNA Packaging Dynamics.

    Serwer, Philip

    International journal of molecular sciences

    2022  Volume 23, Issue 14

    Abstract: The Special Issue "DNA Packaging Dynamics of Bacteriophages" is focused on an event that is among the physically simplest known events with biological character. Thus, phage DNA (and RNA) packaging is used as a relatively accessible model for physical ... ...

    Abstract The Special Issue "DNA Packaging Dynamics of Bacteriophages" is focused on an event that is among the physically simplest known events with biological character. Thus, phage DNA (and RNA) packaging is used as a relatively accessible model for physical analysis of all biological events. A similar perspective motivated early phage-directed work, which was a major contributor to early molecular biology. However, analysis of DNA packaging encounters the limitation that phages vary in difficulty of observing various aspects of their packaging. If a difficult-to-access aspect arises while using a well-studied phage, a counterstrategy is to (1) look for and use phages that provide a better access "window" and (2) integrate multi-phage-accessed information with the help of chemistry and physics. The assumption is that all phages are characterized by the same evolution-derived themes, although with variations. Universal principles will emerge from the themes. A spin-off of using this strategy is the isolation and characterization of the diverse phages needed for biomedicine. Below, I give examples in the areas of infectious disease, cancer, and neurodegenerative disease.
    MeSH term(s) Bacteriophages/genetics ; DNA Packaging ; Genome, Viral ; Humans ; Neurodegenerative Diseases/genetics
    Language English
    Publishing date 2022-07-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23147854
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Optimizing Anti-Viral Vaccine Responses: Input from a Non-Specialist.

    Serwer, Philip

    Antibiotics (Basel, Switzerland)

    2020  Volume 9, Issue 5

    Abstract: Recently, the research community has had a real-world look at reasons for improving vaccine responses to emerging RNA viruses. Here, a vaccine non-specialist suggests how this might be done. I propose two alternative options and compare the primary ... ...

    Abstract Recently, the research community has had a real-world look at reasons for improving vaccine responses to emerging RNA viruses. Here, a vaccine non-specialist suggests how this might be done. I propose two alternative options and compare the primary alternative option with current practice. The basis of comparison is feasibility in achieving what we need: a safe, mass-produced, emerging virus-targeted vaccine on 2-4 week notice. The primary option is the following. (1) Start with a platform based on live viruses that infect bacteria, but not humans (bacteriophages, or phages). (2) Isolate phages (to be called pathogen homologs) that resemble and provide antigenic context for membrane-covered, pathogenic RNA viruses; coronavirus-phage homologs will probably be found if the search is correctly done. (3) Upon isolating a viral pathogen, evolve its phage homolog to bind antibodies neutralizing for the viral pathogen. Vaccinate with the evolved phage homolog by generating a local, non-hazardous infection with the phage host and then curing the infection by propagating the phage in the artificially infecting bacterial host. I discuss how this alternative option has the potential to provide what is needed after appropriate platforms are built.
    Keywords covid19
    Language English
    Publishing date 2020-05-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics9050255
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Using the Past to Maximize the Success Probability of Future Anti-Viral Vaccines.

    Serwer, Philip

    Vaccines

    2020  Volume 8, Issue 4

    Abstract: Rapid obtaining of safe, effective, anti-viral vaccines has recently risen to the top of the international agenda. To maximize the success probability of future anti-viral vaccines, the anti-viral vaccines successful in the past are summarized here by ... ...

    Abstract Rapid obtaining of safe, effective, anti-viral vaccines has recently risen to the top of the international agenda. To maximize the success probability of future anti-viral vaccines, the anti-viral vaccines successful in the past are summarized here by virus type and vaccine type. The primary focus is on viruses with both single-stranded RNA genomes and a membrane envelope, given the pandemic past of influenza viruses and coronaviruses. The following conclusion is reached, assuming that success of future strategies is positively correlated with strategies successful in the past. The primary strategy, especially for emerging pandemic viruses, should be development of vaccine antigens that are live-attenuated viruses; the secondary strategy should be development of vaccine antigens that are inactivated virus particles. Support for this conclusion comes from the complexity of immune systems. These conclusions imply the need for a revision in current strategic planning.
    Keywords covid19
    Language English
    Publishing date 2020-10-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines8040566
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Using the Past to Maximize the Success Probability of Future Anti-Viral Vaccines

    Philip Serwer

    Vaccines, Vol 8, Iss 566, p

    2020  Volume 566

    Abstract: Rapid obtaining of safe, effective, anti-viral vaccines has recently risen to the top of the international agenda. To maximize the success probability of future anti-viral vaccines, the anti-viral vaccines successful in the past are summarized here by ... ...

    Abstract Rapid obtaining of safe, effective, anti-viral vaccines has recently risen to the top of the international agenda. To maximize the success probability of future anti-viral vaccines, the anti-viral vaccines successful in the past are summarized here by virus type and vaccine type. The primary focus is on viruses with both single-stranded RNA genomes and a membrane envelope, given the pandemic past of influenza viruses and coronaviruses. The following conclusion is reached, assuming that success of future strategies is positively correlated with strategies successful in the past. The primary strategy, especially for emerging pandemic viruses, should be development of vaccine antigens that are live-attenuated viruses; the secondary strategy should be development of vaccine antigens that are inactivated virus particles. Support for this conclusion comes from the complexity of immune systems. These conclusions imply the need for a revision in current strategic planning.
    Keywords immune system complexity ; influenza ; pandemics ; virus-caused ; SARS-CoV-2 ; vaccine development strategy ; Medicine ; R ; covid19
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Alzheimer's Disease: A Molecular Model and Implied Path to Improved Therapy.

    Weaver-Rosen, Meagan Susanne / Serwer, Philip

    International journal of molecular sciences

    2024  Volume 25, Issue 6

    Abstract: Amyloid-associated neurodegenerative diseases, including Alzheimer's disease (AD), are characterized by the in-brain accumulation of β-sheet structured protein aggregates called amyloids. However, neither a disease model nor therapy is established. We ... ...

    Abstract Amyloid-associated neurodegenerative diseases, including Alzheimer's disease (AD), are characterized by the in-brain accumulation of β-sheet structured protein aggregates called amyloids. However, neither a disease model nor therapy is established. We review past data and present new, preliminary data and opinions to help solve this problem. The following is the data-derived model/hypothesis. (1) Amyloid-forming proteins have innate immunity functions implemented by conversion to another sheet conformation, α-sheet. (2) In health, α-sheet structured, amyloid-forming proteins inactivate microbes by co-assembly with microbe α-sheets. Amyloid-forming proteins then undergo α-to-β-sheet conversion. (3) In disease, α-sheet-structured, amyloid-forming proteins over-accumulate and are neuron-toxic. This hypothesis includes formation by virus capsid subunits of α-sheets. In support, we find that 5-10 mM methylene blue (MB) at 54 °C has a hyper-expanding, thinning effect on the phage T4 capsid, as seen by negative stain- and cryo-electron microscopy after initial detection by native gel electrophoresis (AGE). Given the reported mild anti-AD effect of MB, we propose the following corollary hypothesis. (1) Anti-AD MB activity is, at least in part, caused by MB-binding to amyloid α-sheet and (2) MB induces the transition to α-sheet of T4 capsid subunits. We propose using AGE of drug incubated T4 to test for improved anti-AD activity.
    MeSH term(s) Humans ; Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Cryoelectron Microscopy ; Amyloid/metabolism ; Amyloidogenic Proteins ; Models, Molecular ; Amyloid beta-Peptides/metabolism
    Chemical Substances Amyloid ; Amyloidogenic Proteins ; Amyloid beta-Peptides
    Language English
    Publishing date 2024-03-20
    Publishing country Switzerland
    Document type Review ; Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25063479
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Optimizing anti-viral vaccine responses: Input from a non-specialist

    Serwer, Philip

    Antibiotics

    Abstract: Recently, the research community has had a real-world look at reasons for improving vaccine responses to emerging RNA viruses. Here, a vaccine non-specialist suggests how this might be done. I propose two alternative options and compare the primary ... ...

    Abstract Recently, the research community has had a real-world look at reasons for improving vaccine responses to emerging RNA viruses. Here, a vaccine non-specialist suggests how this might be done. I propose two alternative options and compare the primary alternative option with current practice. The basis of comparison is feasibility in achieving what we need: a safe, mass-produced, emerging virus-targeted vaccine on 2–4 week notice. The primary option is the following. (1) Start with a platform based on live viruses that infect bacteria, but not humans (bacteriophages, or phages). (2) Isolate phages (to be called pathogen homologs) that resemble and provide antigenic context for membrane-covered, pathogenic RNA viruses; coronavirus-phage homologs will probably be found if the search is correctly done. (3) Upon isolating a viral pathogen, evolve its phage homolog to bind antibodies neutralizing for the viral pathogen. Vaccinate with the evolved phage homolog by generating a local, non-hazardous infection with the phage host and then curing the infection by propagating the phage in the artificially infecting bacterial host. I discuss how this alternative option has the potential to provide what is needed after appropriate platforms are built.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #665441
    Database COVID19

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  7. Article: Using the Past to Maximize the Success Probability of Future Anti-Viral Vaccines

    Serwer, Philip

    Vaccines

    Abstract: Rapid obtaining of safe, effective, anti-viral vaccines has recently risen to the top of the international agenda To maximize the success probability of future anti-viral vaccines, the anti-viral vaccines successful in the past are summarized here by ... ...

    Abstract Rapid obtaining of safe, effective, anti-viral vaccines has recently risen to the top of the international agenda To maximize the success probability of future anti-viral vaccines, the anti-viral vaccines successful in the past are summarized here by virus type and vaccine type The primary focus is on viruses with both single-stranded RNA genomes and a membrane envelope, given the pandemic past of influenza viruses and coronaviruses The following conclusion is reached, assuming that success of future strategies is positively correlated with strategies successful in the past The primary strategy, especially for emerging pandemic viruses, should be development of vaccine antigens that are live-attenuated viruses;the secondary strategy should be development of vaccine antigens that are inactivated virus particles Support for this conclusion comes from the complexity of immune systems These conclusions imply the need for a revision in current strategic planning
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #813263
    Database COVID19

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  8. Article ; Online: Extracellular Interaction of

    Ritter, Samantha / Wright, Elena T / Serwer, Philip

    Viruses

    2023  Volume 15, Issue 12

    Abstract: The following hypothesis proposes non-diffusive, environmental bacteriophage (phage) motion. (1) Some phage-hosting, motile bacteria undergo chemotaxis down ATP concentration gradients to escape lysis-inducing conditions, such as phage infection. (2) ... ...

    Abstract The following hypothesis proposes non-diffusive, environmental bacteriophage (phage) motion. (1) Some phage-hosting, motile bacteria undergo chemotaxis down ATP concentration gradients to escape lysis-inducing conditions, such as phage infection. (2) Some phages respond by non-infective binding to the motile bacteria. (3) When the bacteria reach a lower ATP concentration, which is a condition that signals increased density of phage-susceptible bacteria, the phage converts, Trojan-horse-like, to productive binding and infection. This hypothesis was previously proposed for
    MeSH term(s) Bacteriophages ; Bacillus thuringiensis ; Biofilms ; Phage Therapy ; Adenosine Triphosphate
    Chemical Substances Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2023-12-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v15122409
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Restoring logic and data to phage-cures for infectious disease.

    Serwer, Philip

    AIMS microbiology

    2017  Volume 3, Issue 4, Page(s) 706–712

    Abstract: Antibiotic therapy for infectious disease is being compromised by emergence of multi-drug-resistant bacterial strains, often called superbugs. A response is to use a cocktail of several bacteria-infecting viruses (bacteriophages or phages) to supplement ... ...

    Abstract Antibiotic therapy for infectious disease is being compromised by emergence of multi-drug-resistant bacterial strains, often called superbugs. A response is to use a cocktail of several bacteria-infecting viruses (bacteriophages or phages) to supplement antibiotic therapy. Use of such cocktails is called phage therapy, which has the advantage of response to bacterial resistance that is rapid and not exhaustible. A procedure of well-established success is to make cocktails from stockpiles of stored environmental phages. New phages are added to stockpiles when phage therapy becomes thwarted. The scientific subtext includes optimizing the following aspects: (1) procedure for rapidly detecting, purifying, storing and characterizing phages for optimization of phage cocktails, (2) use of directed evolution in the presence of bacteriostatic compounds to obtain phages that can be most efficiently used for therapy in the presence of these compounds, (3) phage genome sequencing technology and informatics to improve the characterization of phages, and (4) database technology to make optimal use of all relevant information and to rapidly retrieve phages for cocktails that will vary with the infection(s) involved. The use of phage stockpiles has an established record, including a recent major human-therapy success by the US Navy. However, I conclude that most research is not along this track and, therefore, is not likely to lead to real world success. I find that a strong case exists for action to rectify this situation.
    Language English
    Publishing date 2017-08-15
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2471-1888
    ISSN (online) 2471-1888
    DOI 10.3934/microbiol.2017.4.706
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Hypothesis for the cause and therapy of neurodegenerative diseases.

    Serwer, Philip

    Medical hypotheses

    2017  Volume 110, Page(s) 60–63

    Abstract: The cause and therapy of neurodegenerative diseases remain unsolved puzzles. These diseases are correlated with presence of beta sheet-rich amyloid assemblies. Here, I derive and assemble puzzle pieces to obtain a loose end-tying hypothesis for cause ... ...

    Abstract The cause and therapy of neurodegenerative diseases remain unsolved puzzles. These diseases are correlated with presence of beta sheet-rich amyloid assemblies. Here, I derive and assemble puzzle pieces to obtain a loose end-tying hypothesis for cause with direct implications for therapy. I use the following extrapolations to find connectable puzzle pieces: (a) the traditional extrapolation that amyloid/amyloid precursors cause disease, (b) a recent extrapolation that amyloid-forming proteins, some of which are virus protein homologs, are components of an empirically obscure innate immune system that counters insults, including those by both viruses and bacteria, (c) a new extrapolation that various insults produce assemblies with structural features in common and that amyloid-forming, innate immune system proteins recognize these features and, then, counter insults by co-assembly, (d, 1) a second new extrapolation that beta sheet is a common structural feature and is extended during insult-neutralizing co-assembly and (d, 2) an appendix, derived from studies of phages T3 and T4, that most insult-produced assemblies are obscure to current biochemical analysis. The hypothesis is the following. One function of amyloid-forming proteins is non-classical innate immunity to biological insults. This immunity works via beta sheet-extending co-assembly of amyloid-forming proteins with beta sheet-containing insult products. For example, co-assembly with beta sheet-containing viral assembly intermediates inhibits virus production. Amyloid-forming proteins cause neurodegenerative disease when errant, typically overproduced. Other innate immunity systems sometimes exacerbate symptoms. This hypothesis suggests the following therapy, based on manipulating Nature's chemistry. First, conduct directed evolution to obtain low-pathogenicity, chronic symptom-producing viruses with assembly intermediates that co-assemble with and destabilize both amyloid and amyloid sub-assemblies. Then, infect patients with these viruses.
    MeSH term(s) Amyloidogenic Proteins/chemistry ; Amyloidogenic Proteins/immunology ; Animals ; Biological Evolution ; Humans ; Immunity, Innate ; Models, Neurological ; Neurodegenerative Diseases/etiology ; Neurodegenerative Diseases/immunology ; Neurodegenerative Diseases/therapy ; Protein Conformation, beta-Strand ; Viral Proteins/immunology
    Chemical Substances Amyloidogenic Proteins ; Viral Proteins
    Language English
    Publishing date 2017-11-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 193145-3
    ISSN 1532-2777 ; 0306-9877
    ISSN (online) 1532-2777
    ISSN 0306-9877
    DOI 10.1016/j.mehy.2017.11.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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