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      Candidatos potenciales farmacológicos inhibidores de proteasa transmembrana de serina 2 en el tratamiento de 2019-ncov Translated title: Potential pharmacological candidates Transmembrane protease, serine 2 inhibitors 2019-ncov treatment

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          Abstract

          Resumen Introducción: La Enfermedad por coronavirus 2019 (COVID-19) causada por el virus SARS-CoV-2, con característica de infectar el tracto respiratorio causando un síndrome respiratorio agudo como paso inicial para ingresar a la célula huésped el virus usa los receptores ACE II y la proteína transmembrana TMPRSS2 para causar la infección, Por lo que se ha descrito diferentes tipos de fármacos para realizar su inhibición en la adhesión del paso inicial. Metodología: Revisión no sistemática de artículos con la ayuda de palabras clave preestablecidas. Resultados: En esta revisión presentaremos fármacos que inhiben este tipo de receptor, por lo tanto, estos medicamentos podrían considerarse candidatos potenciales para mitigar la propagación del SARS-CoV-2.

          Translated abstract

          Abstract Introduction: Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus with characteristic of infecting the respiratory tract, causing severe acute respiratory syndrome. The virus uses the ACE II receptors and the transmembrane protein TMPRSS2 initial step to enter the host cell, this contribution described different types of drug, to perform its inhibition in initial step adhesion. Methodology: Non-systematic review of articles with the help of preset keywords Results: In this review we will present drugs that inhibitors of this type of receptor therefore these drugs could be considered potential candidates to mitigate the spread of SARS-CoV-2.

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          Most cited references22

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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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            Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient

            This study documents results of SARS-CoV-2 polymerase chain reaction (PCR) testing of environmental surfaces and personal protective equipment surrounding 3 COVID-19 patients in isolation rooms in a Singapore hospital.
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              The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis.

              TMPRSS2 is an androgen-regulated cell-surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastases. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries, we identified a spectrum of TMPRSS2 substrates that include pro-hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-MET receptor tyrosine kinase signaling, and initiated a proinvasive epithelial-to-mesenchymal transition phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment.
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                Author and article information

                Journal
                ars
                Ars Pharmaceutica (Internet)
                Ars Pharm
                Universidad de Granada (Granada, Granada, Spain )
                2340-9894
                December 2020
                : 61
                : 4
                : 253-257
                Affiliations
                [1] Cartagena Bolívar orgnameCorporación Universitaria Rafael Núñez orgdiv1Facultad Ciencias de la Salud orgdiv2Programa de Medicina Colombia
                [3] Cartagena Bolívar orgnameUniversidad de Cartagena orgdiv1Facultad de Ciencias Exactas y Naturales orgdiv2Programa de Biología Colombia
                [2] Cartagena Bolívar orgnameCorporación Universitaria Rafael Núñez Colombia
                Article
                S2340-98942020000400008 S2340-9894(20)06100400008
                10.30827/ars.v61i4.15688
                5bb8ea29-659b-4487-93ff-6fcefaa58a64

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

                History
                : 17 July 2020
                : 12 August 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 22, Pages: 5
                Product

                SciELO Spain

                Categories
                Notas Clínicas

                TMPRSS2,Coronaviridae,ACE II,COVID-19,2019-nCoV
                TMPRSS2, Coronaviridae, ACE II, COVID-19, 2019-nCoV

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