An insight into SARS-CoV-2 membrane protein interaction with spike, envelope, and nucleocapsid proteins

Abstract

Intraviral protein–protein interactions are crucial for replication, pathogenicity, and viral assembly. Among these, virus assembly is a critical step as it regulates the arrangements of viral structural proteins and helps in the encapsulation of genomic material. SARS-CoV-2 structural proteins play an essential role in the self-rearrangement, RNA encapsulation, and mature virus particle formation. In SARS-CoV, the membrane protein interacts with the envelope and spike protein in Endoplasmic Reticulum Golgi Intermediate Complex (ERGIC) to form an assembly in the lipid bilayer, followed by membrane-ribonucleoprotein (nucleocapsid) interaction. In this study, we tried to understand the interaction of membrane protein’s interaction with envelope, spike, and nucleocapsid proteins using protein–protein docking. Further, simulation studies were performed up to 100 ns to examine the stability of protein–protein complexes of Membrane-Envelope, Membrane-Spike, and Membrane-Nucleocapsid proteins. Prime MM-GBSA showed high binding energy calculations for the simulated structures than the docked complex. The interactions identified in our study will be of great importance, as it provides valuable insight into the protein–protein complex, which could be the potential drug targets for future studies.

Communicated by Ramaswamy H. Sarma

Keywords:

• Protein–protein interactions
• binding free energy
• molecular dynamics simulation
• membrane
• envelope
• nucleocapsid
• spike glycoprotein

Acknowledgments

All the authors thank IIT Mandi for the infrastructure.

Disclosure statement

All authors affirm that there are no conflicts of interest.

Authors’ contributions

RG and NG contributed to study supervision and designed the experiment. PK and AK contributed to the acquisition and interpretation of computational data. PK, AK, and RG contributed to paper writing. PK and AK have contributed equally.

Additional information

Funding

RG is thankful to IYBA award from DBT, Government of India (BT/11/IYBA/2018/06) and SERB, Govt. of India (CRG/2019/005603).