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.

Automated summary

The antiviral treatment of SARS-CoV-2 has prompted worldwide research and clinical trials with drugs like lopinavir/ritonavir, darunavir/cobicistat, and remdesivir. Study designs vary greatly and results are often conflicting. Remdesivir is the most commonly used drug in clinical trials, followed by lopinavir/ritonavir, favipiravir, ribavirin, and sofosbuvir.