Tags

Type your tag names separated by a space and hit enter

SARS-CoV-2 host tropism: An in silico analysis of the main cellular factors.
Virus Res. 2020 11; 289:198154.VR

Abstract

Recent reports have shown that small and big felines could be infected by SARS-CoV-2, while other animals, like swines and mice, are apparently not susceptible to this infection. These findings raise the question of the role of cell factors associated with early stages of the viral infection in host selectivity. The cellular receptor for SARS-CoV-2 is the Angiotensin Converting Enzyme (ACE2). Transmembrane protease serine 2 (TMPRSS2) has been shown to prime the viral spike for its interaction with its receptor. GRP78 has also been proposed as a possible co-receptor. In this study, we used several bioinformatics approaches to bring clues in the interaction of ACE2, TMPRSS2, and GRP78 with SARS-CoV-2. We selected several mammalian hosts that could play a key role in viral spread by acting as secondary hosts (cats, dogs, pigs, mice, and ferrets) and evaluated their predicted permissiveness by in silico analysis. Results showed that ionic pairs (salt bridges, N-O pair, and long-range interactions) produced between ACE2 and the viral spike has an essential function in the host interaction. On the other hand, TMPRSS2 and GRP78 are proteins with high homology in all the evaluated hosts. Thus, these proteins do not seem to play a role in host selectivity, suggesting that other factors may play a role in the non-permissivity in some of these hosts. These proteins represent however interesting cell targets that could be explored in order to control the virus replication in humans and in the intermediary hosts.

Authors+Show Affiliations

Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.Department of Neurology and Experimental Therapeutics and Molecular Imaging Laboratory, Massachusetts General Hospital, MA 02129, USA.Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.Unidad de Química Medicinal, Facultad de Farmacia, Universidad Central de Venezuela, Caracas 1041-A, Venezuela. Electronic address: maria.serrano@ucv.ve.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

32918944

Citation

Rangel, H R., et al. "SARS-CoV-2 Host Tropism: an in Silico Analysis of the Main Cellular Factors." Virus Research, vol. 289, 2020, p. 198154.
Rangel HR, Ortega JT, Maksoud S, et al. SARS-CoV-2 host tropism: An in silico analysis of the main cellular factors. Virus Res. 2020;289:198154.
Rangel, H. R., Ortega, J. T., Maksoud, S., Pujol, F. H., & Serrano, M. L. (2020). SARS-CoV-2 host tropism: An in silico analysis of the main cellular factors. Virus Research, 289, 198154. https://doi.org/10.1016/j.virusres.2020.198154
Rangel HR, et al. SARS-CoV-2 Host Tropism: an in Silico Analysis of the Main Cellular Factors. Virus Res. 2020;289:198154. PubMed PMID: 32918944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 host tropism: An in silico analysis of the main cellular factors. AU - Rangel,H R, AU - Ortega,J T, AU - Maksoud,S, AU - Pujol,F H, AU - Serrano,M L, Y1 - 2020/09/09/ PY - 2020/05/29/received PY - 2020/09/01/revised PY - 2020/09/03/accepted PY - 2020/9/13/pubmed PY - 2020/10/31/medline PY - 2020/9/12/entrez KW - COVID-19 KW - GRP78 KW - Receptor ACE2 KW - SARS-CoV-2 KW - TMPRSS2 SP - 198154 EP - 198154 JF - Virus research JO - Virus Res VL - 289 N2 - Recent reports have shown that small and big felines could be infected by SARS-CoV-2, while other animals, like swines and mice, are apparently not susceptible to this infection. These findings raise the question of the role of cell factors associated with early stages of the viral infection in host selectivity. The cellular receptor for SARS-CoV-2 is the Angiotensin Converting Enzyme (ACE2). Transmembrane protease serine 2 (TMPRSS2) has been shown to prime the viral spike for its interaction with its receptor. GRP78 has also been proposed as a possible co-receptor. In this study, we used several bioinformatics approaches to bring clues in the interaction of ACE2, TMPRSS2, and GRP78 with SARS-CoV-2. We selected several mammalian hosts that could play a key role in viral spread by acting as secondary hosts (cats, dogs, pigs, mice, and ferrets) and evaluated their predicted permissiveness by in silico analysis. Results showed that ionic pairs (salt bridges, N-O pair, and long-range interactions) produced between ACE2 and the viral spike has an essential function in the host interaction. On the other hand, TMPRSS2 and GRP78 are proteins with high homology in all the evaluated hosts. Thus, these proteins do not seem to play a role in host selectivity, suggesting that other factors may play a role in the non-permissivity in some of these hosts. These proteins represent however interesting cell targets that could be explored in order to control the virus replication in humans and in the intermediary hosts. SN - 1872-7492 UR - https://www.unboundmedicine.com/medline/citation/32918944/SARS_CoV_2_host_tropism:_An_in_silico_analysis_of_the_main_cellular_factors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-1702(20)31061-3 DB - PRIME DP - Unbound Medicine ER -