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  • 1
    Online Resource
    Online Resource
    Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 47 ( 2020-11-24), p. 29832-29838
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 47 ( 2020-11-24), p. 29832-29838
    Abstract: Effective therapies are urgently needed for the SARS-CoV-2/COVID-19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from large phage-displayed Fab, scFv, and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. A high-affinity Fab was selected from one of the libraries and converted to a full-size antibody, IgG1 ab1, which competed with human ACE2 for binding to RBD. It potently neutralized replication-competent SARS-CoV-2 but not SARS-CoV, as measured by two different tissue culture assays, as well as a replication-competent mouse ACE2-adapted SARS-CoV-2 in BALB/c mice and native virus in hACE2-expressing transgenic mice showing activity at the lowest tested dose of 2 mg/kg. IgG1 ab1 also exhibited high prophylactic and therapeutic efficacy in a hamster model of SARS-CoV-2 infection. The mechanism of neutralization is by competition with ACE2 but could involve antibody-dependent cellular cytotoxicity (ADCC) as IgG1 ab1 had ADCC activity in vitro. The ab1 sequence has a relatively low number of somatic mutations, indicating that ab1-like antibodies could be quickly elicited during natural SARS-CoV-2 infection or by RBD-based vaccines. IgG1 ab1 did not aggregate, did not exhibit other developability liabilities, and did not bind to any of the 5,300 human membrane-associated proteins tested. These results suggest that IgG1 ab1 has potential for therapy and prophylaxis of SARS-CoV-2 infections. The rapid identification (within 6 d of availability of antigen for panning) of potent mAbs shows the value of large antibody libraries for response to public health threats from emerging microbes.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2010197117
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    The opportunistic marine pathogen Vibrio parahaemolyticus becomes virulent by acquiring a plasmid that expresses a deadly toxin
    Proceedings of the National Academy of Sciences ; 2015
    In:  Proceedings of the National Academy of Sciences Vol. 112, No. 34 ( 2015-08-25), p. 10798-10803
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 34 ( 2015-08-25), p. 10798-10803
    Abstract: Acute hepatopancreatic necrosis disease (AHPND) is a severe, newly emergent penaeid shrimp disease caused by Vibrio parahaemolyticus that has already led to tremendous losses in the cultured shrimp industry. Until now, its disease-causing mechanism has remained unclear. Here we show that an AHPND-causing strain of V. parahaemolyticus contains a 70-kbp plasmid (pVA1) with a postsegregational killing system, and that the ability to cause disease is abolished by the natural absence or experimental deletion of the plasmid-encoded homologs of the Photorhabdus insect-related (Pir) toxins PirA and PirB. We determined the crystal structure of the V. parahaemolyticus PirA and PirB (PirA vp and PirB vp ) proteins and found that the overall structural topology of PirA vp /PirB vp is very similar to that of the Bacillus Cry insecticidal toxin-like proteins, despite the low sequence identity ( 〈 10%). This structural similarity suggests that the putative PirAB vp heterodimer might emulate the functional domains of the Cry protein, and in particular its pore-forming activity. The gene organization of pVA1 further suggested that pirAB vp may be lost or acquired by horizontal gene transfer via transposition or homologous recombination.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1503129112
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 3
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    Online Resource
    Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 3 ( 2020-01-21), p. 1438-1446
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 3 ( 2020-01-21), p. 1438-1446
    Abstract: Feline infectious peritonitis virus (FIPV) is an alphacoronavirus that causes a nearly 100% mortality rate without effective treatment. Here we report a 3.3-Å cryoelectron microscopy (cryo-EM) structure of the serotype I FIPV spike (S) protein, which is responsible for host recognition and viral entry. Mass spectrometry provided site-specific compositions of densely distributed high-mannose and complex-type N - glycans that account for 1/4 of the total molecular mass; most of the N-glycans could be visualized by cryo-EM. Specifically, the N-glycans that wedge between 2 galectin-like domains within the S1 subunit of FIPV S protein result in a unique propeller-like conformation, underscoring the importance of glycosylation in maintaining protein structures. The cleavage site within the S2 subunit responsible for activation also showed distinct structural features and glycosylation. These structural insights provide a blueprint for a better molecular understanding of the pathogenesis of FIP.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1908898117
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Voice Therapy for Benign Voice Disorders in the Elderly: A Randomized Controlled Trial Comparing Telepractice and Conventional Face-to-Face Therapy
    American Speech Language Hearing Association ; 2020
    In:  Journal of Speech, Language, and Hearing Research Vol. 63, No. 7 ( 2020-07-17), p. 2132-2140
    Details
    In: Journal of Speech, Language, and Hearing Research, American Speech Language Hearing Association, Vol. 63, No. 7 ( 2020-07-17), p. 2132-2140
    Abstract: Previous studies have reported that voice therapy via telepractice is useful for patients with nodules and muscle tension dysphonia. Nevertheless, telepractice for elderly patients with voice disorders has not yet been investigated. We conducted this study to examine the hypothesis that voice therapy via telepractice is not inferior to conventional voice therapy. Method Eighty patients with dysphonia aged more than 55 years participated in this study from September 2016 to June 2018. After screening the inclusion and the exclusion criteria, 69 patients were randomized into telepractice (33 patients) and conventional (36 patients) groups. The outcome measurements included Voice Handicap Index-10, videolaryngostroboscopy, maximum phonation time, auditory-perceptual evaluation, and acoustic analysis. Paired t test, Wilcoxon signed-ranks test, and repeated measures analysis of variance were used to examine treatment outcomes. Results The diagnoses of voice disorders included atrophy ( n = 33), unilateral vocal paralysis ( n = 13), muscle tension dysphonia ( n = 7), nodules ( n = 6), and polyps ( n = 10). No significant differences were observed in age, sex, and baseline measurements between the two groups. Twenty-five patients in the telepractice group and 24 patients in the control group completed at least four weekly sessions. Significant improvements were observed for all the outcome measures ( p 〈 .05) in both groups. Improvements in Voice Handicap Index-10 in the telepractice group (24.84 ± 5.49 to 16.80 ± 8.94) were comparable to those in the conventional group (22.17 ± 7.29 to 13.46 ± 9.95, p = .764). Other parameters also showed comparable improvements between the two groups without statistically significant differences. Conclusions This is the first randomized controlled trial comparing telepractice and conventional voice therapy in elderly patients with voice disorders. The results showed that the effectiveness of voice therapy via telepractice was not inferior to that of conventional voice therapy, indicating that telepractice can be used as an alternative to provide voice care for elderly patients with vocal disorders.
    Type of Medium: Online Resource
    ISSN: 1092-4388 , 1558-9102
    URL: Article
    DOI: 10.1044/2020_JSLHR-19-00364
    Language: English
    Publisher: American Speech Language Hearing Association
    Publication Date: 2020
    detail.hit.zdb_id: 2070420-3
    SSG: 5,2
    SSG: 7,11
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