Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HCoV-229E)

Authors

Keykavous Parang, Chapman UniversityFollow
Naglaa Salem El-Sayed, Chapman UniversityFollow
Assad J. Kazeminy, Chapman UniversityFollow
Rakesh Tiwari, Chapman UniversityFollow

Document Type

Article

Publication Date

5-17-2020

Abstract

Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. The study revealed that remdesivir exhibited an EC₅₀ value of 0.07 µM against HCoV-229E with TC₅₀ of > 2.00 µM against MRC-5 cells. Parent NRTIs were found to be inactive against (HCoV-229E) at tested concentrations. Among all the NRTIs and 5′-O-fatty acyl conjugates of NRTIs, 5′-O-tetradecanoyl ester conjugate of FTC showed modest activity with EC₅₀ and TC₅₀ values of 72.8 µM and 87.5 µM, respectively. These data can be used for the design of potential compounds against other coronaviruses.

Comments

This article was originally published in Molecules, volume 25, issue 10, in 2020. https://doi.org/10.3390/molecules25102343

This scholarship is part of the Chapman University COVID-19 Archives.

Recommended Citation

Parang K, El-Sayed NS, Kazeminy AJ, Tiwari RK. Comparative antiviral activity of remdesivir and anti-HIV nucleoside analogs against human coronavirus 229E (HCoV-229E). Molecules. 2020;25(10):2343. Published 2020 May 17. https://doi.org/10.3390/molecules25102343

Copyright

The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.