Abstract
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.
Competing Interest Statement
The authors are affiliated with Conduit Computing, a company which is developing a home diagnostic test for COVID-19 (as well as other infectious diseases) called nanoSPLASH.
Footnotes
Figures and text have been revised for clarity and flow. Some minor errors have been corrected. 3M1E data has been moved to supplementary information.