In infected cells, the newly synthesized spike protein in ER is transported first to the Golgi, and then from Golgi to the ERGIC compartment, which is the site of β-coronavirus progeny assembly 8, 9, 10. The trimeric β-coronavirus spike is organized into an ecto-domain, a transmembrane domain, and a cytosolic domain 6, 7 (Fig. Fundamental insights into spike biogenesis will advance the understanding of how β-coronaviruses exploit host resources during viral infection and may potentially lead to the development of novel therapeutics. Current efforts to contain the pandemic are focused primarily on vaccinations using the viral spike protein that is responsible for SARS-CoV-2 entry into host cells 4, 5. Most recently, the novel SARS-CoV-2 has been implicated in the COVID-19 global pandemic that has claimed over four million lives. A decade later, Middle East respiratory syndrome (MERS) was reported in Saudi Arabia in 2012 with over 30% fatality in patients 2, 3. In 2002, the severe acute respiratory syndrome coronavirus (SARS-CoV) was implicated in an epidemic first reported in China before spreading to 27 countries, which resulted in 774 deaths 1. Β-Coronaviruses have been responsible for major human respiratory diseases in the last two decades. Collectively, our investigation on the spike motif identifies key COPI binding determinants with implications for retrograde trafficking. αCOPI residues critical for spike motif binding are elucidated by mutagenesis and crystallography and found to be conserved in the zoonotic reservoirs, bats, pangolins, camels, and in humans. Guided by an in silico analysis of dibasic motifs in the human proteome, we employ mutagenesis and binding assays to show that the spike motif terminal residues are critical modulators of complex dissociation, which is essential for spike release in ERGIC. This motif demonstrates selectivity for αCOPI subunit. Here we identify an extended COPI binding motif in the spike that encompasses the canonical K-x-H dibasic sequence. However, limited residue-level details are available into how the spike interacts with COPI. Β-Coronaviruses such as SARS-CoV-2 hijack coatomer protein-I (COPI) for spike protein retrograde trafficking to the progeny assembly site in endoplasmic reticulum-Golgi intermediate compartment (ERGIC).

Post memorial day covid spike