Elucidation of SARS-CoV-2 budding mechanisms through molecular dynamics simulations of M and E protein complexes

Collins, Logan T.; Elkholy, Tamer; Mubin, Shafat; Hill, David; Williams, Ricky; Ezike, Kayode; Singhal, Ankush

SARS-CoV-2 and other coronaviruses pose major threats to global health, yet computational efforts to understand them have largely overlooked the process of budding, a key part of the coronavirus life cycle. When expressed together, coronavirus M and E proteins are sufficient to facilitate budding into the ER-Golgi intermediate compartment (ERGIC). To help elucidate budding, we ran atomistic molecular dynamics (MD) simulations using the Feig laboratory’s refined structural models of the SARS-CoV-2 M protein dimer and E protein pentamer. Our MD simulations consisted of M protein dimers and E protein pentamers in patches of membrane. By examining where these proteins induced membrane curvature in silico, we obtained insights around how the budding process may occur. The M protein dimers acted cooperatively to induce membrane curvature while E protein pentamers kept the membrane planar. These results could eventually help guide the development of antiviral therapeutics which inhibit coronavirus budding.