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Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity

    Authors: Markus Hoffmann; Heike Hofmann-Winkler; Joan C. Smith; Nadine Krueger; Lambert K. Sorensen; Ole S. Sogaard; Jorgen Bo Hasselstrom; Michael Winkler; Tim Hempel; Lluis Raich; Simon Olsson; Takashi Yamazoe; Katsura Yamatsuta; Hirotaka Mizuno; Stephan Ludwig; Frank Noe; Jason M. Sheltzer; Mads Kjolby; Stefan Poehlmann

    doi:10.1101/2020.08.05.237651 Date: 2020-08-05 Source: bioRxiv

    Antiviral therapy is urgently needed to combat the coronavirus disease MESHD 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). The protease inhibitor camostat mesylate inhibits SARS-CoV-2 infection MESHD of lung cells by blocking the virus-activating host cell protease TMPRSS2. Camostat mesylate has been approved for treatment of pancreatitis MESHD pancreatitis HP in Japan and is currently being repurposed for COVID-19 treatment. However, potential mechanisms of viral resistance as well as camostat mesylate metabolization and antiviral activity of metabolites are unclear. Here, we show that SARS-CoV-2 can employ TMPRSS2-related host cell proteases for activation and that several of them are expressed in viral target cells. However, entry mediated by these proteases was blocked by camostat mesylate. The camostat metabolite GBPA inhibited the activity of recombinant TMPRSS2 with reduced efficiency as compared to camostat mesylate and was rapidly generated in the presence of serum SERO. Importantly, the infection MESHD experiments in which camostat mesylate was identified as a SARS-CoV-2 inhibitor involved preincubation of target cells with camostat mesylate in the presence of serum SERO for 2 h and thus allowed conversion of camostat mesylate into GBPA. Indeed, when the antiviral activities of GBPA and camostat mesylate were compared in this setting, no major differences were identified. Our results indicate that use of TMPRSS2-related proteases for entry into target cells will not render SARS-CoV-2 camostat mesylate resistant. Moreover, the present and previous findings suggest that the peak concentrations of GBPA established after the clinically approved camostat mesylate dose (600 mg/day) will result in antiviral activity.

    Patients with COVID-19 Interstitial Pneumonia MESHD Pneumonia HP Exhibit Pancreatic Hyperenzymemia and Not Acute Pancreatitis HP Pancreatitis MESHD

    Authors: Raffaele Pezzilli; Stefano Centanni; Michele Mondoni; Rocco F. Rinaldo; Matteo Davì; Rossana Stefanelli; GianVico Melzi d’Eril; Alessandra Barassi

    doi:10.21203/rs.3.rs-50275/v1 Date: 2020-07-28 Source: ResearchSquare

    Background and aims: Gastrointestinal manifestations of COVID-19 have been well established, but pancreatic involvement is under debate. The aim of the study is to evaluate the presence of acute pancreatitis HP pancreatitis MESHD in COVID-19 patients and to assess the frequency of pancreatic hyperenzymemia. Methods: From April 1st 2020 to April 30th 2020, 110 consecutive patients (69 males TRANS, 41 females TRANS; mean age TRANS 63.0 years, range 24-93 years) met these criteria and were enrolled in the study.. The clinical data and serum SERO activity of pancreatic amylase and lipase were assayed in all patients using commercially available kits. Results: None of the patients studied developed clinical signs or morphological alterations compatible with acute pancreatitis HP pancreatitis MESHD. However, it was found that 24.5% of the patients had amylase values above 53 IU/L and 16.4% had lipase values above 300 IU/. Only one patient (0.9%) had both amylase and lipase values in excess of three-fold the upper normal limit without clinical signs of pancreatitis MESHD pancreatitis HP. Conclusions: The presence of pancreatic hyperenzymemia in a patient with COVID-19 requires the management of these patients be guided by clinical evaluation and not merely by evaluation of the biochemical results.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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