by Tired: Remdesivir Wired: Merimopodib Inspired: Both Merimopodib (of which I just read for the first time) is an inhibitor of an enzyme used to make Guanosine. Viruses need a lot of Guanosine (and other nucleosides) to reproduce, so it is an antiviral. It can be taken orally and there is a known safe dose. A preprint asserts that a combination of Remdesivir and Merimopodib completely blocks SARS-CoV-2 replication in vitro. Here is the abstract The IMPDH inhibitor merimepodib provided in combination with the adenosine analogue remdesivir reduces SARS-CoV-2 replication to undetectable levels in vitro [version 1; peer review: awaiting peer review] Natalya Bukreyeva, Rachel A. Sattler, Emily K. Mantlo1, Timothy Wanninger, John T. Manning, Cheng Huang, Slobodan
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Tired: Remdesivir
Wired: Merimopodib
Inspired: Both
Merimopodib (of which I just read for the first time) is an inhibitor of an enzyme used to make Guanosine. Viruses need a lot of Guanosine (and other nucleosides) to reproduce, so it is an antiviral. It can be taken orally and there is a known safe dose.
A preprint asserts that a combination of Remdesivir and Merimopodib completely blocks SARS-CoV-2 replication in vitro.
Here is the abstract
The IMPDH inhibitor merimepodib provided in combination with the adenosine analogue remdesivir reduces SARS-CoV-2 replication to undetectable levels in vitro [version 1; peer review: awaiting peer review]
Natalya Bukreyeva, Rachel A. Sattler, Emily K. Mantlo1, Timothy Wanninger, John T. Manning, Cheng Huang, Slobodan Paessler, Jerome B. Zeldis
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BRIEF REPORT
The IMPDH inhibitor merimepodib provided in combination with the adenosine analogue remdesivir reduces SARS-CoV-2 replication to undetectable levels in vitro [version 1; peer review: awaiting peer review]
Natalya Bukreyeva1, Rachel A. Sattler1, Emily K. Mantlo1, Timothy Wanninger1, John T. Manning https://orcid.org/0000-0002-2130-20541, Cheng Huang1, Slobodan Paessler1, Jerome B. Zeldis2
Abstract
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.