Comparative study of SARS-CoV-2 infection in different cell types: Biophysical-computational approach to the role of potential receptors.

González-Paz, Lenin, Alvarado, María José, Hurtado-León, María Laura, Lossada, Carla, Vera-Villalobos, Joan, Loroño, Marcos, Paz, J L, Jeffreys, Laura ORCID: https://orcid.org/0000-0002-0607-6116, Torres, F Javier and Alvarado, Ysaias J (2022) 'Comparative study of SARS-CoV-2 infection in different cell types: Biophysical-computational approach to the role of potential receptors.'. Computers in Biology and Medicine, Vol 142, e105245.

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Abstract

Cellular susceptibility to SARS-CoV-2 infection in the respiratory tract has been associated with the ability of the virus to interact with potential receptors on the host membrane. We have modeled viral dynamics by simulating various cellular systems and artificial conditions, including macromolecular crowding, based on experimental and transcriptomic data to infer parameters associated with viral growth and predict cell susceptibility. We have accomplished this based on the type, number and level of expression of the angiotensin-converting enzyme 2 (ACE2), transmembrane serine 2 (TMPRSS2), basigin2 (CD147), FURIN protease, neuropilin 1 (NRP1) or other less studied candidate receptors such as heat shock protein A5 (HSPA5) and angiotensin II receptor type 2 (AGTR2). In parallel, we studied the effect of simulated artificial environments on the accessibility to said proposed receptors. In addition, viral kinetic behavior dependent on the degree of cellular susceptibility was predicted. The latter was observed to be more influenced by the type of proteins and expression level, than by the number of potential proteins associated with the SARS CoV-2 infection. We predict a greater theoretical propensity to susceptibility in cell lines such as NTERA-2, SCLC-21H, HepG2 and Vero6, and a lower theoretical propensity in lines such as CaLu3, RT4, HEK293, A549 and U-251MG. An important relationship was observed between expression levels, protein diffusivity, and thermodynamically favorable interactions between host proteins and the viral spike, suggesting potential sites of early infection other than the lungs. This research is expected to stimulate future quantitative experiments and promote systematic investigation of the effect of crowding presented here.

Item Type:	Article
Subjects:	QU Biochemistry > Cells and Genetics > QU 375 Cell physiology QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 506 COVID-19
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.compbiomed.2022.105245
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	07 Apr 2022 14:04
Last Modified:	20 Jan 2023 02:02
URI:	https://archive.lstmed.ac.uk/id/eprint/19937

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