UC San Diego

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS2) is a novel epidemic strain of Betacoronaviruses responsible for the Covid-19 pandemic. This virus, and its corresponding disease has claimed millions of lives and caused major obstructions to social and economic platforms around the world. Other notable Betacoronaviruses include the 2003 SARS1 which caused a brief epidemic in China, and the 2011 Middle East Respiratory Syndrome Virus (MERS) which affects northern Africa and central Asia to this day. Despite issuing multiple FDA emergency-use authorized vaccines for the virus, symptomatic breakthrough cases are still possible largely due to already established variants of the SARS2 virus, in particular the delta-variant. With such a large spread, and propensity to evolve, the Betacoronaviruses are likely to remain a challenge to civilization along with the seasonal flu. In any case, preparation against novel Betacoronaviruses is a necessity. In this review, we investigate the early replication stages of Coronaviruses, focusing on SARS1/2. We discuss the proteins associated with genome replication, and the formation of the coronaviral replication organelle, and the discovery of a novel putative coronaviral nuclear pore protein complex. Despite major differences in amino acid sequences, the proteins associated with early replication share strong structural homology. Additionally, stages of membrane rearrangements are shared amongst all the coronaviruses. Understanding the shared mechanisms of replication amongst these viruses is the first step in discovering potential drug targets for coronavirus antivirals.