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      Tmprss2 specific miRNAs as promising regulators for SARS-CoV-2 entry checkpoint

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Graphical abstract

          Highlights

          • Post transcriptional regulators miRNAs may be potential Biodrugs for coronaviruses.

          • Computer aided screening identified 3 miRNAs targeting Tmprss2 in CoV2 management.

          • hsa-miR-214, hsa-miR-98 and hsa-miR-32 recognized as potential binders in Tmprss2.

          • miRNA target validation for TMPRSS2 in Caco-2 promises molecular therapy for CoV2.

          • hsa-miR32 a novel potential therapeutics with maximum suppression of TMPRSS2 protein.

          Abstract

          Tmprss2 is an emerging molecular target which guides cellular infections of SARS-CoV-2, has been earmarked for interventions against the viral pathologies. The study aims to computationally screen and identifies potential miRNAs, following in vitro experimental validation of miRNA-mediated suppression of Tmprss2 for early prevention of COVID-19. Pool of 163 miRNAs, scrutinized for Tmprss2 binding with three miRNA prediction algorithms, ensued 11 common miRNAs. Further, computational negative energies for association, corroborated miRNA-Tmprss2 interactions, whereas three miRNAs (hsa-miR-214, hsa-miR-98 and hsa-miR-32) based on probability scores ≥0.8 and accessibility to Tmprss2 target have been selected in the Sfold tool. Transfection of miRNA(s) in the Caco-2 cells, quantitatively estimated differential expression, confirming silencing of Tmprss2 with maximum gene suppression by hsa-miR-32 employing novel promising role in CoV-2 pathogenesis. The exalted binding of miRNAs to Tmprss2 and suppression of later advocates their utility as molecular tools for prevention of SARS-CoV-2 viral transmission and replication in humans.

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          Most cited references48

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          Is Open Access

          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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              Characterization of a novel coronavirus associated with severe acute respiratory syndrome.

              P Rota (2003)
              In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closely related to any of the previously characterized coronaviruses.
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                Author and article information

                Journal
                Virus Res
                Virus Res
                Virus Research
                Elsevier B.V.
                0168-1702
                1872-7492
                8 January 2021
                March 2021
                8 January 2021
                : 294
                : 198275
                Affiliations
                [a ]Animal Biochemistry Division, ICAR-National Dairy Research Institute, Karnal, Haryana, 132001, India
                [b ]Virus Research and Diagnostic Laboratory, Kalpana Chawla Government Medical College, Karnal, Haryana, 132001, India
                [c ]Centre for Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, 110012, India
                [d ]Multidisciplinary Clinical Translational Research, Translational Health Science and Technology Institute, Faridabad, Haryana, 121001, India
                Author notes
                [* ]Corresponding author at: Translational Health Science and Technology Institute, (An autonomous institute of the Department of Biotechnology, Government of India), NCR Biotech Science Cluster, 3rd Milestone, Faridabad–Gurugram Expressway, PO box #04, Faridabad, Haryana.
                [** ]Co-corresponding author at: Animal Biochemistry Division, National Dairy Research Institute, Karnal, Haryana, 132001, India.
                Article
                S0168-1702(20)31182-5 198275
                10.1016/j.virusres.2020.198275
                7833564
                33359190
                2c7cf5a0-f2ba-451e-979f-ba6696e59adb
                © 2020 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 17 September 2020
                : 27 November 2020
                : 17 December 2020
                Categories
                Article

                Microbiology & Virology
                covid-19,hsa-mir-214,hsa-mir-98,hsa-mir-32,tmprss2
                Microbiology & Virology
                covid-19, hsa-mir-214, hsa-mir-98, hsa-mir-32, tmprss2

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