PT  - JOURNAL ARTICLE
AU  - Logan Thrasher 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/2021/11/10/2021.07.26.453874.short
4100  - http://biorxiv.org/content/early/2021/11/10/2021.07.26.453874.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. Multiple M protein dimers acted together to induce global membrane curvature through protein-lipid interactions while E protein pentamers kept the membrane planar. These results could eventually help guide development of antiviral therapeutics which inhibit coronavirus budding.Competing Interest StatementThe authors are affiliated with Conduit Computing, a company which is developing diagnostic tests for COVID-19 as well as other infectious diseases.