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RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
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Aprotinin Inhibits SARS-CoV-2 Replication.

Denisa Bojkova1, Marco Bechtel1, Katie-May McLaughlin2

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Cells
|November 4, 2020
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The protease inhibitor aprotinin effectively inhibited SARS-CoV-2 replication at therapeutic concentrations. Aprotinin may help control COVID-19 early by compensating for downregulated host proteases.

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2019-nCoVCOVID-19antiviralaprotinindrug discoverysevere acute respiratory syndrome coronavirussevere acute respiratory syndrome coronavirus 2

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Area of Science:

  • Virology
  • Biochemistry
  • Pharmacology

Background:

  • Severe acute respiratory syndrome virus 2 (SARS-CoV-2) causes the COVID-19 pandemic.
  • Protease inhibitors are explored for inhibiting virus entry by blocking spike protein cleavage.
  • Host cell protease inhibitors are downregulated during SARS-CoV-2 replication.

Purpose of the Study:

  • To investigate the antiviral activity of protease inhibitors against SARS-CoV-2.
  • To determine if aprotinin can inhibit SARS-CoV-2 replication.
  • To explore aprotinin's potential in managing COVID-19.

Main Methods:

  • Testing aprotinin and SERPINA1/alpha-1 antitrypsin for SARS-CoV-2 inhibition.
  • Analyzing proteomics and translatome data to understand host-pathogen interactions.
  • Evaluating aprotinin's efficacy in various cell types (Caco2, Calu-3, bronchial epithelial cells) and against multiple virus isolates.

Main Results:

  • Aprotinin, but not SERPINA1, inhibited SARS-CoV-2 replication at therapeutically achievable concentrations.
  • Proteomics and translatome data revealed downregulation of host protease inhibitors during SARS-CoV-2 replication.
  • Aprotinin demonstrated anti-SARS-CoV-2 activity across different cell models and virus strains.

Conclusions:

  • Therapeutic concentrations of aprotinin exhibit anti-SARS-CoV-2 activity.
  • Aprotinin may counteract the downregulation of host proteases during viral replication.
  • Aprotinin aerosol could be a potential therapeutic for early SARS-CoV-2 control and preventing severe COVID-19.