Antiviral Drug-Membrane Permeability: the Viral Envelope and Cellular Organelles

TL;DR

This paper introduces a computational model to rapidly assess drug permeability through viral and cellular membranes, aiding in the efficient identification of effective antiviral compounds like those for SARS-CoV-2.

Contribution

The study presents a novel, flexible computational approach that predicts drug membrane permeability considering both drug properties and membrane characteristics.

Findings

Negative correlation between permeation speed and drug bioavailability.

Model accurately predicts drug permeability across different membranes.

Applicable to a wide range of molecules and biological membranes.

Abstract

To shorten the time required to find effective new drugs, like antivirals, a key parameter to consider is membrane permeability, as a compound intended for an intracellular target with poor permeability will have low efficacy. Here, we present a computational model that considers both drug characteristics and membrane properties for the rapid assessment of drugs permeability through the coronavirus envelope and various cellular membranes. We analyze 79 drugs that are considered as potential candidates for the treatment of SARS-CoV-2 and determine their time of permeation in different organelle membranes grouped by viral baits and mammalian processes. The computational results are correlated with experimental data, present in the literature, on bioavailability of the drugs, showing a negative correlation between fast permeation and most promising drugs. This model represents an important tool capable of evaluating how permeability affects the ability of compounds to reach both intended and unintended intracellular targets in an accurate and rapid way. The method is general and flexible and can be employed for a variety of molecules, from small drugs to nanoparticles, as well to a variety of biological membranes.