tetano
Editor, Senior Moderator
2020 May 17;25(10):E2343.
doi: 10.3390/molecules25102343.
Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs Against Human Coronavirus 229E (HCoV-229E)
Keykavous Parang[SUP] 1 [/SUP], Naglaa Salem El-Sayed[SUP] 1 2 [/SUP], Assad J Kazeminy[SUP] 1 3 [/SUP], Rakesh K Tiwari[SUP] 1 [/SUP]
Affiliations
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 EC[SUB]50[/SUB] value of 0.07 ?M against HCoV-229E with TC[SUB]50[/SUB] of > 2.00 ?M 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 EC[SUB]50[/SUB] and TC[SUB]50[/SUB] values of 72.8 ?M and 87.5 ?M, respectively. These data can be used for the design of potential compounds against other coronaviruses.
Keywords: HCoV-229E; NRTIs; RNA polymerase; SARS-COV-2; antiviral; remdesivir.
doi: 10.3390/molecules25102343.
Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs Against Human Coronavirus 229E (HCoV-229E)
Keykavous Parang[SUP] 1 [/SUP], Naglaa Salem El-Sayed[SUP] 1 2 [/SUP], Assad J Kazeminy[SUP] 1 3 [/SUP], Rakesh K Tiwari[SUP] 1 [/SUP]
Affiliations
- PMID: 32429580
- DOI: 10.3390/molecules25102343
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 EC[SUB]50[/SUB] value of 0.07 ?M against HCoV-229E with TC[SUB]50[/SUB] of > 2.00 ?M 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 EC[SUB]50[/SUB] and TC[SUB]50[/SUB] values of 72.8 ?M and 87.5 ?M, respectively. These data can be used for the design of potential compounds against other coronaviruses.
Keywords: HCoV-229E; NRTIs; RNA polymerase; SARS-COV-2; antiviral; remdesivir.