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A lesson from an old friend: high molecular weight kininogen (HMWK) impact in COVID-19.
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  • Chiara Colarusso,
  • Michela Terlizzi,
  • Aldo Pinto,
  • Rosalinda Sorrentino
Chiara Colarusso
University of Salerno

Corresponding Author:[email protected]

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Michela Terlizzi
University of Salerno
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Aldo Pinto
University of Salerno
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Rosalinda Sorrentino
University of Salerno
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a newly identified coronavirus which has spread from China to the rest of the world causing the pandemic coronavirus disease 19 (COVID-19). It has fatality rate that floats from 5 to 15% and the symtoms are fever, cough, myalgia and/or fatigue up to dyspnea, responsible for hospitalization and in most of the cases of artificial oxygenation. In the attempt to understand how the virus spreads and how to pharmacologically abolish it, it was highlighted that SARS-CoV2 infects human cells by means of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin-like protease (3CLpro), also known as Mpro. Once bound to its receptor ACE2, the other two proteases, in concert with the receptor-mediated signaling, allow virus replication and spread throughout the body. Our attention has been focused on the role of ACE2 in that its blockade by the virus increases Bradykinin and its metabolites, well known to facilitate inflammation in the lung (responsible for cough and fever), facilitate both the coagulation and complement system, three mechanisms that are typical of angioedema, cardiovascular dysfunction and sepsis, pathologies which symptoms occur in COVID-19 patients. Thus, we propose to pharmacologically block the kallicrein-kinin system upstream bradykinin and the ensuing inflammation, coagulation and complement activation by means of lanadelumab, which is a clinically approved drug for hereditary angioedema.
07 May 2020Submitted to British Journal of Pharmacology
09 May 2020Submission Checks Completed
09 May 2020Assigned to Editor
11 May 2020Reviewer(s) Assigned
18 May 2020Editorial Decision: Revise Minor
22 May 20201st Revision Received
25 May 2020Submission Checks Completed
25 May 2020Assigned to Editor
26 May 2020Reviewer(s) Assigned
29 May 2020Editorial Decision: Accept