PT - JOURNAL ARTICLE AU - Logan T. Collins AU - Tamer Elkholy AU - Shafat Mubin AU - David Hill AU - Ricky Williams AU - Kayode Ezike AU - Ankush Singhal TI - Elucidation of SARS-CoV-2 budding mechanisms through molecular dynamics simulations of M and E protein complexes AID - 10.1101/2021.07.26.453874 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.07.26.453874 4099 - http://biorxiv.org/content/early/2021/08/20/2021.07.26.453874.short 4100 - http://biorxiv.org/content/early/2021/08/20/2021.07.26.453874.full AB - 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 StatementThe 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.