Faculty Collaboration Database

Inhibition of Human Coronaviruses by Antimalarial Peroxides. ACS Infect Dis 2021 Jul 09;7(7):1985-1995

Date

03/31/2021

Pubmed ID

33783182

DOI

10.1021/acsinfecdis.1c00053

Scopus ID

2-s2.0-85105043981 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

As the toll of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues, efforts are ongoing to identify new agents and repurpose safe drugs for its treatment. Antimalarial peroxides have reported antiviral and anticancer activities. Here, we evaluated the in vitro activities of artesunate (AS) and two ozonides (OZ418 and OZ277) against human α-coronavirus NL63 and β-coronaviruses OC43 and SARS-CoV-2 in several cell lines. OZ418 had the best selectivity index (SI) in NL63-infected Vero cells and MK2 cells. The overall SI of the tested compounds was cell-type dependent. In OC43-infected human foreskin fibroblasts, AS had the best cell-associated SI, ≥17 μM, while the SI of OZ418 and OZ277 was ≥12 μM and ≥7 μM, respectively. AS did not inhibit SARS-CoV-2 in either Vero or Calu-3 cells. A comparison of OZ418 and OZ277 activity in SARS-CoV2-infected Calu-3 cells revealed similar EC₅₀ (5.3 μM and 11.6 μM, respectively), higher than the EC₅₀ of remdesivir (1.0 ± 0.1 μM), but the SI of OZ418 was higher than OZ277. A third ozonide, OZ439, inhibited SARS-CoV-2 efficiently in Vero cells, but compared to OZ418 in Calu-3 cells, it showed higher toxicity. Improved inhibition of SARS-CoV-2 was observed when OZ418 was used together with remdesivir. Although the EC₅₀ of ozonides might be clinically achieved in plasma after intravenous administration, sustained virus suppression in tissues will require further considerations, including drug combination. Our work supports the potential repurposing of ozonides and calls for future in vivo models.

Author List

Ghosh AK, Miller H, Knox K, Kundu M, Henrickson KJ, Arav-Boger R

Authors

Ravit Boger MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Ayan K. Ghosh PhD Research Scientist I in the Pediatrics department at Medical College of Wisconsin
Kelly J. Henrickson MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antimalarials
Humans
Peroxides
RNA, Viral
Vero Cells