Repositioning HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors for the treatment of SARS-CoV-2 infection and COVID-19

  • Aims: SARS-CoV-2 is a single-stranded RNA virus which is part of the ß-coronavirus family (like SARS 2002 and MERS 2012). The high prevalence of hospitalization and mortality, in addition to the lack of vaccines and therapeutics, forces scientists and clinicians around the world to evaluate new therapeutic options. One strategy is the repositioning of already known drugs, which were approved drugs for other indications. Subject and method: SARS-CoV-2 entry inhibitors, RNA polymerase inhibitors, and protease inhibitors seem to be valuable targets of research. At the beginning of the pandemic, the webpage listed n=479 clinical trials related to the antiviral treatment of SARS-CoV-2 (01.04.2020, “SARS-CoV-2,” “COVID-19,” “antivirals,” “therapy”), of which n=376 are still accessible online in January 2021 (10.01.2021). Taking into account further studies not listed in the CTG webpage, this narrative review appraises HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors as promising candidates for the treatment of COVID-19. Results: Lopinavir/ritonavir, darunavir/cobicistat, remdesivir, tenofovir-disoproxilfumarate, favipriravir, and sofosbuvir are evaluated in clinical studies worldwide. Study designs show a high variability and results often are contradictory. Remdesivir is the drug, which is deployed in nearly 70% of the reviewed clinical trials, followed by lopinavir/ritonavir, favipiravir, ribavirine, and sofosbuvir. Discussion: This review discusses the pharmacological/clinical background and questions the rationale and study design of clinical trials with already approved HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors which are repositioned during the SARS-CoV-2 pandemic worldwide. Proposals are made for future study design and drug repositioning of approved antiretroviral compounds.

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Author:Nils von HentigORCiDGND
Parent Title (English):European journal of clinical pharmacology
Place of publication:Berlin ; Heidelberg ; New York
Document Type:Article
Date of Publication (online):2021/03/04
Date of first Publication:2021/03/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/10/20
Tag:HIV protease inhibitors; RNA polymerase inhibitors; Repositioning drugs; SARS-CoV-2
Page Number:11
First Page:1297
Last Page:1307
Open Access funding enabled and organized by Projekt DEAL.
Institut: Medizin
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0