Programme

P.64 -- Poster, VCTP-49

Date: Friday, 2 August 2024

Time: 08:30 - 10:00

Neuropilin-1 protein may serve as a receptor for SARS-CoV-2 infection: Evidence from molecular dynamics simulations

Hoang Linh Nguyen1,2, Ho Khac Hieu3,4, Nguyen Quoc Thai5,6, Nguyen Thi Ai Nhung7, and Mai Suan Li8

1Institute of Fundamental and Applied Sciences, Duy Tan University, Ho Chi Minh City 700000, Vietnam 2Faculty of Environmental and Natural Sciences, Duy Tan University, Da Nang 550000, Vietnam 3Institute of Research and Development, Duy Tan University, 03 Quang Trung, Hai Chau, Da Nang 550000, Viet Nam 4Faculty of Environmental and Natural Sciences, Duy Tan University, 03 Quang Trung, Hai Chau, Da Nang 550000, Viet Nam 5Faculty of Physics, VNU University of Science, Vietnam National University, 334 Nguyen Trai, Hanoi 100000, Vietnam 6Dong Thap University, 783 Pham Huu Lau Street, Ward 6, Cao Lanh City, Dong Thap, Vietnam 7Department of Chemistry, University of Sciences, Hue University, Hue, Vietnam 8Institute of Physics, Polish Academy of Sciences, al. Lotnikow 32/46, 02-668, Warsaw, Poland

Human cell angiotensin converting enzyme 2 (ACE2) is the most popular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but other receptors have been observed in experiments. Neuropilin-1 protein (NRP1) is one of them, but the mechanism of its binding to the wild type (WT) and different variants of the virus remains unclear at the atomic level. In this work, all-atom umbrella sampling simulations were performed to clarify the binding mechanism of NRP1 to the spike protein fragment 679–685 of the WT, Delta, and Omicron BA.1 variants. We found that the Delta variant binds most strongly to NRP1, while Omicron BA.1 slightly decreases the binding affinity to NRP1 compared to WT, and the van der Waals interaction plays a key role in stabilizing the complexes studied. The change in protonation state of the His amino acid results in different binding free energies between variants. Consistent with the experiment, lowering the pH was shown to increase the binding affinity of the virus to NRP1. Our results indicate that Delta and Omicron mutations not only affect fusogenicity but also affect NRP1 binding.

Presenter: Nguyen Hoang Linh