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. 2021 Feb 12;11:585331. doi: 10.3389/fphar.2020.585331

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Copyright © 2021 Lem, Opook, Lee, Chee, Lawson and Chin.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Potential drug candidate to treat COVID-19 manufactured by Gilead Sciences to treat COVID-19, remdesivir (Kim et al., 2019). The addition of 3″ hydroxyl group (blue circle) in remdesivir inhibits the replication of the MERS RNA strand after a few cycles of nucleotide addition, which shields this antiviral drug from removal by coronavirus proofreading enzymes that abolish nucleotide analogs whereas the nitrogens (yellow circle) function as a proton donor and acceptor for a hydrogen bond to a uracil base as an identical binding site of double stranded RNA in adenosine. The phosphate group (green circle) is created as a protecting group or McGuigan ProTide to transport this antiviral compound into cells through phosphorylation, which is identical to a normal nucleotide triphosphate and recognized by polymerases in the cell. The important and unique part for this nucleotide analog is the addition of the 1′ cyano group (red circle) to eliminate the side effect of blockage of the mitochondrial RNA polymerase exhibited in mice.