Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications Bálint Mészáros1 (ORCID: 0000-0003-0919-4449) Hugo Sámano-Sánchez1 (ORCID: 0000-0003-4744-4787) Jesús Alvarado-Valverde1,2 (ORCID: 0000-0003-0752-1151) Jelena Čalyševa1,2 (ORCID: 0000-0003-1047-4157) Elizabeth Martínez-Pérez1,3 (ORCID: 0000-0003-4411-976X) Renato Alves1 (ORCID: 0000-0002-7212-0234) Manjeet Kumar1 (ORCID: 0000-0002-3004-2151) Email:
[email protected] Friedrich Rippmann4 (ORCID: 0000-0002-4604-9251) Lucía B. Chemes5 (ORCID: 0000-0003-0192-9906) Email:
[email protected] Toby J. Gibson1 (ORCID: 0000-0003-0657-5166) Email:
[email protected] 1Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany 2Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences 3Laboratorio de bioinformática estructural, Fundación Instituto Leloir, C1405BWE, Buenos Aires, Argentina 4Computational Chemistry & Biology, Merck KGaA, Frankfurter Str. 250, 64293 Darmstadt, Germany 5Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín. Av. 25 de Mayo y Francia S/N, CP1650 Buenos Aires, Argentina Keywords: COVID-19 / Coronavirus / Receptor-Mediated Endocytosis / Autophagy / SLiM / ELM Server / Host-Pathogen Interaction / ACE2 / Integrins / Integrin αvβ3 / Integrin α5β1 / Host Targeted Therapy / Tyrosine Kinase Abstract The primary cell surface receptor for SARS-CoV-2 is the angiotensin-converting enzyme 2 (ACE2). Recently it has been noticed that the viral Spike protein has an RGD motif, suggesting that cell surface integrins may be co-receptors. We examined the sequences of ACE2 and integrins with the Eukaryotic Linear Motif resource, ELM, and were presented with candidate short linear motifs (SLiMs) in their short, unstructured, cytosolic tails with potential roles in endocytosis, membrane dynamics, autophagy, cytoskeleton and cell signalling.