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

Preview	Text 2021-01-20_-_Manuscript_Frontiers_clean.pdf - Accepted Version Available under License Creative Commons: Attribution (CC-BY). Download (786kB) | Preview
Preview	Text fphar-12-625678.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (1MB) | Preview

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.

Interest & Impact

Downloads

205 since deposited on 03 Feb 2021
42 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item