Emerging mutations in envelope protein of SARS-CoV-2 and their effect on thermodynamic properties

Kejie Mou; Mohnad Abdalla; Dong Qing Wei; Muhammad Tahir Khan; Madeeha Shahzad Lodhi; Doaa B Darwish; Mohamed Sharaf; Xudong Tu

doi:10.1016/j.imu.2021.100675

Emerging mutations in envelope protein of SARS-CoV-2 and their effect on thermodynamic properties

Inform Med Unlocked. 2021:25:100675. doi: 10.1016/j.imu.2021.100675. Epub 2021 Jul 27.

Authors

Kejie Mou¹, Mohnad Abdalla², Dong Qing Wei^{3

4}, Muhammad Tahir Khan⁵, Madeeha Shahzad Lodhi⁵, Doaa B Darwish⁶, Mohamed Sharaf^{7

8}, Xudong Tu⁹

Affiliations

¹ Department of Neurosurgery, Bishan Hospital of Chongqing, Chongqing, China.
² Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Shandong Province, 250012, PR China.
³ State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint International Research Laboratory of Metabolic & Developmental Sciences and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, PR China.
⁴ Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen, Guangdong, 518055, PR China.
⁵ Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, KM Defence Road, Lahore, Pakistan, 58810.
⁶ Department of Biology, Faculty of Science, University of Tabuk, 71491, Saudi Arabia.
⁷ Department of Biochemistry and Molecular Biology, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, PR China.
⁸ Department of Biochemistry, Faculty of Agriculture, AL-Azhar University, Nasr City, Cairo, 11751, Egypt.
⁹ Chongqing Medical and Pharmaceutical College, Chongqing, China.

Abstract

Structural proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are potential drug targets due to their role in the virus life cycle. The envelope (E) protein is one of the structural proteins; plays a critical role in virulency. However, the emergence of mutations oftenly leads to drug resistance and may also play a vital role in virus stabilization and evolution. In this study, we aimed to identify mutations in E proteins that affect the protein stability. About 0.3 million complete whole genome sequences were analyzed to screen mutations in E protein. All these mutations were subjected to stability prediction using the DynaMut server. The most common mutations that were detected at the C-terminal domain, Ser68Phe, Pro71Ser, and Leu73Phe, were examined through molecular dynamics (MD) simulations for a 100ns period. The sequence analysis shows the existence of 259 mutations in E protein. Interestingly, 16 of them were detected in the DFLV amino acid (aa) motif (aa72-aa75) that binds the host PALS1 protein. The results of root mean square deviation, fluctuations, radius of gyration, and free energy landscape show that Ser68Phe, Pro71Ser, and Leu73Phe are exhibiting a more stabilizing effect. However, a more comprehensive experimental study may be required to see the effect on virus pathogenicity. Potential antiviral drugs, and vaccines may be developed used after screening the genomic variations for better management of SARS-CoV-2 infections.

Keywords: Antiviral drugs; Envelope; Genome; Mutations; SARS-CoV-2; Stability.