Theoretical Efficacy of Possible Inhibitors of SARS-CoV-2 Cell Recognition and Their Effect on Viral Dynamics in Different Cell Types: Computational Biology and Prediction from <i>in Vitro</i> Experimental Data

It has been reported that the susceptibility of cells to be infected by SARS-CoV-2 may be facilitated by various proteins that behave as potential receptors for the virus. To explore this, we have modeled viral dynamics by simulating various cellular systems (Vero E6, HeLa, HEK293 and CaLu3) in the presence and absence of drugs (anthelmintic, ARBs, anticoagulant, serine protease inhibitor, antimalarials and NSAID) proposed to affect cellular recognition by the spike protein from experimental data. Simulated cell systems exhibited similar susceptibility to SARS-CoV-2 infection. CaLu3 was the most susceptible to SARS-CoV-2 infection, likely due to the effect of receptors other than ACE2, which may statistically contribute to most of the observed susceptibility. All tested compounds bound to the spike protein in a thermodynamically favorable and stable manner throughout the study time. The anticoagulant nafamostat presented the most favorable characteristics in terms of thermodynamics, kinetics, theoretical antiviral activity, and potential safety (toxicity) associated with SARS-CoV-2 spike protein-mediated infections in the cell lines tested. This study contributes with mathematical and bioinformatic models for the search of optimal cell lines for the evaluation and detection of compounds, especially in mechanism of action studies focusing on repurposed drugs. These observations must be experimentally demonstrated and this research is expected to stimulate future quantitative experiments.