Structures and dynamics of the novel S1/S2 protease cleavage site loop of the SARS-CoV-2 spike glycoprotein.

Lemmin, Thomas; Kalbermatter, David; Harder, Daniel; Plattet, Philippe; Fotiadis, Dimitrios (2020). Structures and dynamics of the novel S1/S2 protease cleavage site loop of the SARS-CoV-2 spike glycoprotein. Journal of structural biology: X, 4, p. 100038. Elsevier 10.1016/j.yjsbx.2020.100038

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At the end of 2019, a new highly virulent coronavirus known under the name SARS-CoV-2 emerged as a human pathogen. One key feature of SARS-CoV-2 is the presence of an enigmatic insertion in the spike glycoprotein gene representing a novel multibasic S1/S2 protease cleavage site. The proteolytic cleavage of the spike at this site is essential for viral entry into host cells. However, it has been systematically abrogated in structural studies in order to stabilize the spike in the prefusion state. In this study, multi-microsecond molecular dynamics simulations and ab initio modeling were leveraged to gain insights into the structures and dynamics of the loop containing the S1/S2 protease cleavage site. They unveiled distinct conformations, formations of short helices and interactions of the loop with neighboring glycans that could potentially regulate the accessibility of the cleavage site to proteases and its processing. In most conformations, this loop protrudes from the spike, thus representing an attractive SARS-CoV-2 specific therapeutic target.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Faculty Institutions > NCCR TransCure
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research

UniBE Contributor:

Kalbermatter, David, Harder, Daniel, Plattet, Philippe, Fotiadis, Dimitrios José


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health








Barbara Franziska Järmann-Bangerter

Date Deposited:

11 Jan 2021 10:54

Last Modified:

05 Dec 2022 15:44

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Ab initio modelling Coronavirus Furin cleavage site Molecular dynamics simulation SARS-CoV-2 Spike glycoprotein




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