Candidate drugs against SARS-CoV-2 and COVID-19

  • McKee, Dwight L.
  • Sternberg, Ariane
  • Stange, Ulrike
  • Laufer, Stefan
  • Naujokat, Cord

  • aIntegrative Cancer Consulting, Aptos, CA, USA

    bCenter and Network for Targeted Oncology, Muehlackerweg 8, D-69239, Heidelberg, Germany

    cDepartment of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität, Tübingen and Tuebingen Center for Academic Drug Discovery, Auf Der Morgenstelle 8, 72076, Tuebingen, Germany

    dInstitute of Immunology, University of Heidelberg, Im Neuenheimer Feld 305, D-69120, Heidelberg, Germany

* Corresponding author.

E-mail address:[email protected].

Received 27 March 2020; Received in revised form 20 April 2020; Accepted 22 April 2020

Available online 29 April 2020

Pharmacological Research 157:p 104859, July 2020. | DOI: 10.1016/j.phrs.2020.104859

Graphical abstract

Coronavirus SARS-CoV-2 enters host cells via ligation of its spike protein (S glycoprotein) with host cell ACE2 receptor that is primed by TMPRSS2 protease. ACE2- and TMPRSS2-mediated cell entry can be blocked by experimental and established drugs. Virus replication and assembly can be inhibited by antiviral drugs targeting viral RNA-dependent RNA polymerase (RdRp) and main protease (3Clpro).

Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may limit spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.

Copyright © 2020Elsevier, Inc.