Variable Macro X Domain of SARS-CoV-2 Retains the Ability to Bind ADP-ribose

David N. Frick; Rajdeep S. Virdi; Nemanja Vuksanovic; Narayan Dahal; Nicholas R Silvaggi

The development of antivirals targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the present COVID-19 pandemic, 1 will most likely focus on viral proteins and enzymes needed for replication. 2 Like other coronaviruses, SARS-CoV-2 has a large positive sense (+)RNA genome over 30,000 nucleotides long with several open reading frames. Most of the proteins that form the viral replicase are encoded by the "rep 1ab" reading frame, which codes for a 7,096 amino acid-long polyprotein that is ultimately processed into at least 15 functional peptides, five of which are only produced by a translational frameshift event occurring after nsp10 (Fig. 1) . Parts of the SARS-CoV-2 rep 1ab polyprotein are very similar to the rep 1ab protein of the coronavirus that caused the SARS epidemic in 2003 (which will be referred to here as SARS-CoV-1), suggesting the that drugs targeting the SARS-CoV-1 nsp5-14 might be effective against SARS-CoV-2. However, some portions of the SARS rep 1ab polyproteins are quite different.