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Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Molecules 2020 ; 25 (10): ä Nephropedia Template TP
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Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs Against Human Coronavirus 229E (HCoV-229E) #MMPMID32429580
Parang K; El-Sayed NS; Kazeminy AJ; Tiwari RK
Molecules 2020[May]; 25 (10): ä PMID32429580show ga
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(50) value of 0.07 microM against HCoV-229E with TC(50) of > 2.00 microM 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(50) and TC(50) values of 72.8 microM and 87.5 microM, respectively. These data can be used for the design of potential compounds against other coronaviruses.