The IMPDH inhibitor merimepodib provided in combination with the adenosine analogue remdesivir reduces SARS-CoV-2 replication to undetectable levels in vitro
| Autor: | Emily K. Mantlo, Rachel A. Sattler, Natalya Bukreyeva, John T. Manning, Timothy G. Wanninger, Cheng Huang, Jerome B. Zeldis, Slobodan Paessler |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
General Immunology and Microbiology Coronavirus disease 2019 (COVID-19) business.industry Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 030106 microbiology General Medicine medicine.disease_cause Adenosine Virology General Biochemistry Genetics and Molecular Biology In vitro 03 medical and health sciences Titer 030104 developmental biology Merimepodib Vero cell Medicine General Pharmacology Toxicology and Pharmaceutics business Coronavirus medicine.drug |
| Zdroj: | F1000Research. 9:361 |
| ISSN: | 2046-1402 |
| DOI: | 10.12688/f1000research.23639.1 |
| Popis: | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing COVID-19 pandemic, which has resulted in over 2.5 million confirmed cases and 170,000 deaths worldwide as of late April 2020. The pandemic currently presents major public health and economic burdens worldwide. No vaccines or therapeutics have been approved for use to treat COVID-19 cases in the United States despite the growing disease burden, thus creating an urgent need for effective treatments. The adenosine analogue remdesivir (REM) has recently been investigated as a potential treatment option, and has shown some activity in limiting SARS-CoV-2 replication. We previously reported that the IMPDH inhibitor merimepodib (MMPD) provides a dose-dependent suppression of SARS-CoV-2 replication in vitro. Here, we report that a 4-hour pre-treatment of Vero cells with 2.5µM MMPD reduces the infectious titer of SARS-CoV-2 more effectively than REM at the same concentration. Additionally, pre-treatment of Vero cells with both REM and MMPD in combination reduces the infectious titer of SARS-CoV-2 to values below the detectable limit of our TCID50 assay. This result was achieved with concentrations as small as 1.25 µM MMPD and 2.5 µM REM. At concentrations of each agent as low as 0.31 µM, significant reduction of viral production occurred. This study provides evidence that REM and MMPD administered in combination might be an effective treatment for COVID-19 cases. |
| Databáze: | OpenAIRE |
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