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      Nanoparticle composite TPNT1 is effective against SARS-CoV-2 and influenza viruses

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          Abstract

          A metal nanoparticle composite, namely TPNT1, which contains Au-NP (1 ppm), Ag-NP (5 ppm), ZnO-NP (60 ppm) and ClO 2 (42.5 ppm) in aqueous solution was prepared and characterized by spectroscopy, transmission electron microscopy, dynamic light scattering analysis and potentiometric titration. Based on the in vitro cell-based assay, TPNT1 inhibited six major clades of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with effective concentration within the range to be used as food additives. TPNT1 was shown to block viral entry by inhibiting the binding of SARS-CoV-2 spike proteins to the angiotensin-converting enzyme 2 (ACE2) receptor and to interfere with the syncytium formation. In addition, TPNT1 also effectively reduced the cytopathic effects induced by human (H1N1) and avian (H5N1) influenza viruses, including the wild-type and oseltamivir-resistant virus isolates. Together with previously demonstrated efficacy as antimicrobials, TPNT1 can block viral entry and inhibit or prevent viral infection to provide prophylactic effects against both SARS-CoV-2 and opportunistic infections.

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          Most cited references60

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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              Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

              Summary A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.
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                Author and article information

                Contributors
                jmfang@ntu.edu.tw
                pcyang@ntu.edu.tw
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                22 April 2021
                22 April 2021
                2021
                : 11
                : 8692
                Affiliations
                [1 ]GRID grid.19188.39, ISNI 0000 0004 0546 0241, Department of Clinical Laboratory Sciences and Medical Biotechnology, , National Taiwan University College of Medicine, ; No. 1, Sec. 1, Ren-Ai Rd., Taipei, 10002 Taiwan
                [2 ]GRID grid.412094.a, ISNI 0000 0004 0572 7815, Department of Laboratory Medicine, , National Taiwan University Hospital, Chung-Shan South Rd., ; No. 7, Taipei, 10002 Taiwan
                [3 ]GRID grid.260565.2, ISNI 0000 0004 0634 0356, Department and Graduate Institute of Microbiology and Immunology, , National Defense Medical Center, ; Taipei, 11490 Taiwan
                [4 ]Tripod Nano Technology, No. 171, Sec. 1, Mei Shi Rd., Yang Mei District, Taoyuan, 32656 Taiwan
                [5 ]GRID grid.28665.3f, ISNI 0000 0001 2287 1366, The Genomics Research Center, , Academia Sinica, ; No. 128, Sec. 2, Academia Rd., Taipei, 11529 Taiwan
                [6 ]GRID grid.19188.39, ISNI 0000 0004 0546 0241, Department of Chemistry, , National Taiwan University, ; No. 1, Sec. 4, Roosevelt Rd., Taipei, 10607 Taiwan
                [7 ]GRID grid.19188.39, ISNI 0000 0004 0546 0241, Department of Internal Medicine, , National Taiwan University Hospital and National Taiwan University College of Medicine, ; No. 7, Chung-Shan South Rd., Taipei, 10002 Taiwan
                [8 ]GRID grid.28665.3f, ISNI 0000 0001 2287 1366, Institute of Biomedical Sciences, , Academia Sinica, ; No. 128, Sec. 2, Academia Rd., Taipei, 11529 Taiwan
                Article
                87254
                10.1038/s41598-021-87254-3
                8062499
                33888738
                7a5a1479-ce95-4560-ba9a-4d6edfffc7fb
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 28 July 2020
                : 25 March 2021
                Funding
                Funded by: Ministry of Science and Technology
                Award ID: MOST107-2320-B-002-016-MY3
                Award ID: MOST107-2320-B-002-016-MY3
                Award ID: MOST107-2320-B-002-016-MY3
                Award ID: MOST107-2320-B-002-016-MY3
                Award ID: MOST 108-3114-Y-001-002
                Award ID: MOST 108-3114-Y-001-002
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001869, Academia Sinica;
                Award ID: AS-SUMMIT-108
                Award ID: AS-SUMMIT-108
                Award ID: AS-SUMMIT-108
                Award ID: AS-SUMMIT-108
                Award Recipient :
                Funded by: Ministry of Science and Technolog
                Award ID: MOST 107-0210-01-19-01
                Award ID: MOST 107-0210-01-19-01
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                nanoparticles,antiviral agents
                Uncategorized
                nanoparticles, antiviral agents

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