Weak Point of SARS-CoV-2: Human and Viral Ion Channels under External Physical Fields

Abstract

The ionic E-nanochannel (viroporin) is the weak point of SARS-CoV-2, the virus responsible for the (still threatening) COVID-19 since it is vital to the virus's budding and propagation. Therefore, targeting it to disable its functions ought to incapacitate, or at least weaken, the virus. The ionic currents inside this channel could be affected and disturbed by direct physical attack via the actions of external fields. The paper presents the first step towards the application of such methods in the fight against the current pandemic, numerical simulations of external fields' impact on ionic currents through viral channels. These simulations-based on the actual, detailed physical nanostructure of ionic channels, measured experimentally and reported in the literature-show that external physical fields can diminish the channel's currents and that the lower the channel's selectivity, the stronger the effect. Simulations suggest that SARS-CoV-2 E-viroporin is almost non-selective, which means that the whole virus ought to be highly vulnerable to the actions of external physical fields, much more vulnerable than the much more selective human cell ionic channels. If corroborated by experiment, this observation may result in an innovative method of dealing with the recent pandemic caused by SARS-CoV-2 and other similar viruses.

Keywords: Brownian motions; SARS-CoV-2; ionic nanochannels; numerical simulations; selectivity; ultrasound; viroporins; viruses.

Figure 1

The general geometrical structure of a biological ionic nanochannel. Red lines: schematic presentation of the simplified structure of the channel in question; black shape: a sketch of the geometrical structure of ionic biochannels based on KcsA K⁺ channel presented in Figure 1 in [13] and Figure 3 in [14]. The similar general structure of the SARS-CoV-2 E-viroporin is discussed in [3]. EV: external vestibule, SF: selectivity filter (single-file motion), WC: water cavity, G: gate, IV: internal vestibule. R: [numbers, nm] describe radii r of cylindrical fragments of the simplified model, z: [numbers, nm] describe distance along the channel longitudinal axis from the external entrance (z = 0) towards the interior (z = 10).

Figure 2

Relative diminishing of current DI = $<$ I_D(t)$/I$₀(t)$>$ as the function of field strength D (in arbitrary units). (A): Cation, (B): Anion currents; black: prokaryotic and eukaryotic (incl. human), red: viral (incl. SARS-CoV-1), blue: SARS-CoV-2 channels.