https://socictopen.socict.org/files/original/0e80589cc49d9c24526a18472ddec514.pdf 7367b68e97f417fb9d641f179164c987 Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Coronavirus Description An account of the resource Dominio científico: Coronavirus Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site Creator An entity primarily responsible for making the resource Ashita Singh, Neil Carragher, Robin Fahraeus, Kathryn Ball, Ted R Hupp, Umesh Kalathiya, Monikaben Padariya, Javier Antonio Alfaro, Juergen Haas, Maciej Bagiński, Alison Daniels, Marcos Mayordomo, Małgorzata Lisowska, Judith Nicholson Description An account of the resource An important stage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) life cycle is the binding of the spike (S) protein to the angiotensin converting enzyme-2 (ACE2) host cell receptor. Therefore, to explore conserved features in spike protein dynamics and to identify potentially novel regions for drugging, we measured spike protein variability derived from 791 viral genomes and studied its properties by molecular dynamics (MD) simulation. The findings indicated that S2 subunit (heptad-repeat 1 (HR1), central helix (CH), and connector domain (CD) domains) showed low variability, low fluctuations in MD, and displayed a trimer cavity. By contrast, the receptor binding domain (RBD) domain, which is typically targeted in drug discovery programs, exhibits more sequence variability and flexibility. Interpretations from MD simulations suggest that the monomer form of spike protein is in constant motion showing transitions between an “up” and “down” state. In addition, the trimer cavity may function as a “bouncing spring” that may facilitate the homotrimer spike protein interactions with the ACE2 receptor. The feasibility of the trimer cavity as a potential drug target was examined by structure based virtual screening. Several hits were identified that have already been validated or suggested to inhibit the SARS-CoV-2 virus in published cell models. In particular, the data suggest an action mechanism for molecules including Chitosan and macrolides such as the mTOR (mammalian target of Rapamycin) pathway inhibitor Rapamycin. These findings identify a novel small molecule binding-site formed by the spike protein oligomer, that might assist in future drug discovery programs aimed at targeting the coronavirus (CoV) family of viruses. Date A point or period of time associated with an event in the lifecycle of the resource 2020 Subject The topic of the resource molecular docking, variability, Molecular dynamics, spike glycoprotein, SARS-CoV-2, Coronavirus disease 2019 (COVID-19) Identifier An unambiguous reference to the resource within a given context DOI: 10.3390/jcm9051473 Source A related resource from which the described resource is derived Journal of Clinical Medicine Publisher An entity responsible for making the resource available MDPI AG Coverage The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant Medicine