Modeling of SARS-CoV-2 treatment effects for informed drug repurposing

Kern, Charlotte; Schöning, Verena; Chaccour, Carlos; Hammann, Felix (2021). Modeling of SARS-CoV-2 treatment effects for informed drug repurposing. Frontiers in Pharmacology, 12 Frontiers 10.3389/fphar.2021.625678

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Several repurposed drugs are currently under investigation in the fight against coronavirus disease 2019 (COVID-19). Candidates are often selected solely by their effective concentrations in vitro, an approach that has largely not lived up to expectations in COVID-19. Cell lines used in in vitro experiments are not necessarily representative of lung tissue. Yet, even if the proposed mode of action is indeed true, viral dynamics in vivo, host response, and concentration-time profiles must also be considered. Here we address the latter issue and describe a model of human SARS-CoV-2 viral kinetics with acquired immune response to investigate the dynamic impact of timing and dosing regimens of hydroxychloroquine, lopinavir/ritonavir, ivermectin, artemisinin, and nitazoxanide.
We observed greatest benefits when treatments were given immediately at the time of diagnosis. Even interventions with minor antiviral effect may reduce host exposure if timed correctly. Ivermectin seems to be at least partially effective: given on positivity, peak viral load dropped by 0.3-0.6 log units and exposure by 8.8-22.3%. The other drugs had little to no appreciable effect. Given how well previous clinical trial results for hydroxychloroquine and lopinavir/ritonavir are explained by the models presented here, similar strategies should be considered in future drug candidate prioritization efforts.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Kern, Charlotte; Schöning, Verena and Hammann, Felix

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 610 Medicine & health > 615 Pharmacology & therapeutics, prescription drugs

ISSN:

1663-9812

Publisher:

Frontiers

Language:

English

Submitter:

Felix Hammann

Date Deposited:

03 Feb 2021 11:31

Last Modified:

25 Mar 2021 13:47

Publisher DOI:

10.3389/fphar.2021.625678

BORIS DOI:

10.48350/151549

URI:

https://boris.unibe.ch/id/eprint/151549

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