Three‐Dimensional Visualization of Remdesivir and the SARS‐CoV‐2 RdRp

Eid, Asal; Kalyanaraman, Karshana; Nguyen, Binh; Dale, Sierra; Rusch‐Salazar, Laura

The SARS‐CoV‐2 virus, which causes the COVID‐19 disease, has been a focus of concern around the world, setting records as a modern‐day pandemic. The Center for Disease Control has confirmed over 86 million cases in the world with over 1.9 million confirmed deaths as of January 5, 2021. SARS‐CoV‐2 continues to be a serious threat to global public health, leaving a distinct footprint in human history. Our research visualizes and contextualizes the mechanism of remdesivir, an antiviral nucleotide analog prodrug. Remdesivir targets the viral RNA‐dependent RNA polymerase (RdRp) to inhibit replication of the virus. This process is facilitated by a subunit replication‐and‐transcription complex of three major nonstructural proteins (nsps): nsp7, nsp8, and nsp12. With our three‐dimensional model (PDB ID 7BV2), we depict the mechanism of remdesivir inhibition of the copying of the viral RNA template through the central channel of RdRp by terminating chain elongation. Our protein model will guide other researchers and students through the mechanism of action of remdesivir and emphasizes the role of this adenosine nucleotide analogue as it binds to the RNA primer. Our model illustrates how remdesivir impacts viral replication by inhibiting the viral RdRp of SARS‐CoV‐2.