Using wide biological pores to cap and contain the COVID-19 spike protein

Geometric analysis shows that the spike (S) protein in the COVID-19 virus (SARS-Cov-2) can fully or partially enter into the channel of a wide biological pore like perforin (PFN) or streptolysin (SLO) when the latter is anchored in a bilayer lipid membrane. The PFN channel is a β barrel formed from multiple monomers, for example a ~14 nm diameter channel is formed from 22 monomers. Coincidentally the wide canopy of S (which has three identical chains) has an enclosing diameter of ~14 nm. While inside the channel peripheral residues in the canopy may bind with residues on the pore side of the barrel. If there are no adverse cross-reactions this would effectively prevent S from interacting with a target cell. Calculations with data obtained from PDB and other sources show that there are ~12 peripheral residue triples in S within a circle of diameter ~14 nm that can potentially bind with 22 exposed residues in each barrel monomer. The revised Miyazawa-Jernighan matrix is used to calculate the binding energy of canopy-PFN barrel residue pairs. The results show a large number of binding pairs over distances of up to 38 Å into the pore. This geometric view of capture and containment points to the possibility of using biological pores to neutralize SARS-Cov-2 in its many variant forms. Some necessary conditions that must be satisfied for such neutralization to occur are noted. A wide pore (such as PFN or SLO) can also be used in an electrolytic cell to detect the presence of SARS-Cov-2, which would cause a large-sized blockade of the base current (the ionic current in a fully open pore). It can further be used to quantify the virus level in the sample. Solid-state pores, which have several advantages over biological ones, can be used instead; immune rejection is not an issue and there is no need for the spike or the virus to bind to the pore.

Using wide biological pores to cap and contain the COVID-19 spike protein

Geometric analysis shows that the spike (S) protein in the COVID-19 virus (SARS-Cov-2) can fully or partially enter into the channel of a wide biological pore like perforin (PFN) or streptolysin (SLO) when the latter is anchored in a bilayer lipid membrane. The PFN channel is a β barrel formed from multiple monomers, for example a ~14 nm diameter channel is formed from 22 monomers. Coincidentally the wide canopy of S (which has three identical chains) has an enclosing diameter of ~14 nm. While inside the channel peripheral residues in the canopy may bind with residues on the pore side of the barrel. If there are no adverse cross-reactions this would effectively prevent S from interacting with a target cell. Calculations with data obtained from PDB and other sources show that there are ~12 peripheral residue triples in S within a circle of diameter ~14 nm that can potentially bind with 22 exposed residues in each barrel monomer. The revised Miyazawa-Jernighan matrix is used to calculate the binding energy of canopy-PFN barrel residue pairs. The results show a large number of binding pairs over distances of up to 38 Å into the pore. This geometric view of capture and containment points to the possibility of using biological pores to neutralize SARS-Cov-2 in its many variant forms. Some necessary conditions that must be satisfied for such neutralization to occur are noted. A wide pore (such as PFN or SLO) can also be used in an electrolytic cell to detect the presence of SARS-Cov-2, which, by blocking the pore would cause a near total blockade of the base current (the ionic current in a fully open pore).

Using wide biological pores to cap and contain the COVID-19 spike protein

Geometric analysis shows that the spike (S) protein in the COVID-19 virus (SARS-Cov-2) can fully or partially enter into the channel of a wide biological pore like perforin (PFN) or streptolysin (SLO) when the latter is anchored in a bilayer lipid membrane. The PFN channel is a β barrel formed from multiple monomers, for example a ~14 nm diameter channel is formed from 22 monomers. Coincidentally the wide canopy of S (which has three identical chains) has an enclosing diameter of ~14 nm. While inside the channel peripheral residues in the canopy may bind with residues on the pore side of the barrel. If there are no adverse cross-reactions this would effectively prevent S from interacting with a target cell. Calculations with data obtained from PDB and other sources show that there are ~12 peripheral residue triples in S within a circle of diameter ~14 nm that can potentially bind with 22 exposed residues in each barrel monomer. The revised Miyazawa-Jernighan matrix is used to calculate the binding energy of canopy-PFN barrel residue pairs. The results show a large number of binding pairs over distances of up to 38 Å into the pore. This geometric view of capture and containment points to the possibility of using biological pores to neutralize SARS-Cov-2 in its many variant forms. Some necessary conditions that must be satisfied for such neutralization to occur are noted.

Experimental study of the small-diameter channel and shaped-charge jet penetration effect

The paper focuses on experiments carried out to determine the effect of a small-diameter channel, passed by a shaped-charge jet before interacting with an obstacle, on its penetrating action. These experiments were conducted in relation to the study of the features of shaped-charge jet motion through the cavity of an elongated solenoid with electromagnetic stabilization of the jet stretching process. For this purpose, steel sleeves with a channel were installed in front of the shaped charge, which made it possible to simulate the mechanical factors affecting the shaped-charge jet when it moves in the air channel. For the conditions implemented in the experiments, it was found that in the absence of collisions of the shaped-charge jet with the channel walls, the penetration depth decreases insignificantly, i.e. within 5%. In experiments in which there were traces of contact interaction with the shaped-charge jet on the channel surface, a significant decrease in the penetrating action was recorded.

Direct numerical simulation of high aspect ratio spanwise-aligned bars

We conduct minimal-channel direct numerical simulations of turbulent flow over two-dimensional rectangular bars aligned in the spanwise direction. This roughness has often been described as $d$-type, as the roughness function $\unicode[STIX]{x0394}U^{+}$ is thought to depend only on the outer-layer length scale (pipe diameter, channel half-height or boundary layer thickness). This is in contrast to conventional engineering rough surfaces, named $k$-type, for which $\unicode[STIX]{x0394}U^{+}$ depends on the roughness height, $k$. The minimal-span rough-wall channel is used to circumvent the high cost of simulating high Reynolds number flows, enabling a range of bars with varying aspect ratios to be investigated. The present results show that increasing the trough-to-crest height, $k$, of the roughness while keeping the width between roughness bars, ${\mathcal{W}}$, fixed in viscous units, results in non-$k$-type behaviour although this does not necessarily indicate $d$-type behaviour. Instead, for deep surfaces with $k/{\mathcal{W}}\gtrsim 3$, the roughness function appears to depend only on ${\mathcal{W}}$ in viscous units. In these situations, the flow no longer has any information about how deep the roughness is and instead can only ‘see’ the width of the fluid gap between the bars.