Michael Davis, LeShaundria Brown, Tra'Mya Lauderdale, Ryan Billings, Valeanna Adams, Serena Barnhill, Ntirenganyi Karamba, Melanie Van Stry, Candace Jones Carter

This Jmol Exploration was created using the Jmol Exploration Webpage Creator from the MSOE Center for BioMolecular Modeling.

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Exploration Content

Exploring the Mechanisms of Antiviral Therapeutics: A 3D Model of SARS-CoV-2 RdRp in Complex with Remdesivir

The recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) causes coronavirus disease 2019 (COVID-19), a respiratory disease affecting the human population worldwide. SARS-CoV-2 replication requires the RNA dependent RNA polymerase (RdRp) complex, composed of non-structural proteins (nsp) 7, 8, and 12. Nsp 7 and 8 function as a primase, whereas nsp12 functions as RdRp for replication and transcription. This polymerase is the target of the antiviral drug remdesivir, an adenosine monophosphate analog. During RNA replication catalyzed by RdRp, remdesivir is covalently attached to the growing RNA strand, resulting in chain termination. Here, we designed a 3-dimensional (3D) model of the SARS-COV-2 nsp12-nsp7-nsp8 RdRp complex bound to template-primer double-stranded (ds)RNA and remdesivir using Jmol and PDB 7BV2 cryo-EM structure (Yin et al., 2020). The 3D model shows the nsp12 subunit bound to dsRNA template and growing RNA strand that forms a corkscrew-like structure within the center channel. The model highlights specific residues aspartic760, valine557, and serine861 within the active site and the interactions of the template-primer RNA strands with remdesivir. An additional 3D model illustrates the structural similarity of remdesivir to adenosine monophosphate. These 3D models enable students to visualize complex biomolecules and understand mechanisms of therapeutics.

Remdesevir: Carbon Yellow, CPK

RNA Primer: Purple

RNA Template: Orange
Hydrogen Bonds: White Nsp12: Blue [67,67,255] Nsp 8: Red([255,76,76]) Nsp 7: Light Green [144,238,144] D760-A- Aspartic Acid: Pink [255,0,255] V557-V- Valine: Grey [16,80,80] S861-S- Serine: Turquoise

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This displays the RdRp bound to remdesivir, and highlights parts of the model. The non-structural protein(Nsp) 12 is colored Blue and the first to be highlighted. Next is Nsp 7 which is Light Green, and after is Nsp 8 colored red. Then we zoom in to get a closer look at the Remdesivir, Adenine, and the active site.

SARS-CoV-2-RdRp in Complex with Remdesivir

A closer look of the Remdesivir highlighting the structural differences between Adenosine and Remdesivir.


A closer look at adenosine highlighting the difference in the structure from Remdesivir.


Remedesivir is a nucleotide analog that has some structural similarity to adenosine triphosphate. For example, the nitrogenous base can form hydrogen bond with uracil mimicking the base-pairing between adenine and uracil.

Structural differences between remdesivir and adenosine monophosphate: The functional group added to 1' carbon on ribose is a nitrile, also called cyano or organo cyanide, and contains a carbon-nitrogen triple bond. This substitution prevents binding to host cell RNA polymerase. Also there is a C-nucleoside bond at 1' carbon instead of the C-N glycosidic bond found in adenosine.


Here is the RNA template and Primer bound to Remdesivir.

The RNA template is orange and the Primer is purple. From the top view you can see where Remdesivir is covalently attached and results in chain termination.


Beigel JH, et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Nov 5;383(19):1813-1826. doi: 10.1056/NEJMoa2007764. Epub 2020 Oct 8. PMID: 32445440; PMCID: PMC7262788.

Hillen, H.S., Kokic, G., Farnung, L., Dienemann, C., Tegunov, D., Cramer, P. (2020) Structure of replicating SARS-CoV-2 polymerase. Nature,

Oldach. L.. Anatomy of a molecule. What makes remdesivir unique? ASBMB today. March 17, 2020.

Wang, Q., et al. (2020) Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase. Cell 182: 1-12

Yin, W., et al. (2020). Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science, 368(6498), 1499. doi:10.1126/science.abc1560

Zhai, Y.J., Sun, F., Li, X., Pang, H., Xu, X., Bartlam, M., Rao, Z. (2005) Insights into SARS-CoV transcription and replication from the structure of the nsp7-nsp8 hexadecamer. Nat Struct Mol Biol 12: 980-986.