Research Ideas and Outcomes :
Research Idea
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Corresponding author: Georgios Dougas (georgiosdougas@yahoo.com)
Academic editor: Editorial Secretary
Received: 30 May 2023 | Accepted: 11 Oct 2023 | Published: 16 Oct 2023
© 2023 Georgios Dougas
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation:
Dougas G (2023) Electromagnetic radiation as antiviral treatment with a focus on Rabies post-exposure prophylaxis. Research Ideas and Outcomes 9: e107227. https://doi.org/10.3897/rio.9.e107227
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Shortwave and microwave diathermy devices are commonly used in physical therapy as heating treatment. The rise in temperature occurs due to the flow of electric current in the treated area. Ions are evenly distributed in a predicted pattern from skin to deeper tissues. We hypothesise that the diathermy physiotherapy devices (DPDs) can be repurposed as a means of neutralisation of the Rabies virus (RABV) by exploiting the generated electric charges. In order to minimise the ohmic heating of the tissue, the pulsed output of the diathermy devices is preferred where the ‘on’ time of active energy emission is considerably shorter than the ‘off’ time. RABV proteins mediating cell invasion, cytoplasmic replication and budding, contain polar components that can be adversely affected by non-thermal electric phenomena. Repurposed DPDs can replace the Rabies immunoglobulin (RIG) by targeting the site of inoculation i.e. the area of the animal bite, provided that the delivered electric charges can reduce pathogenicity by altering key viral proteins. The modality is advantageous compared to conventional RIG since it can theoretically neutralise all Lyssavirus species, is not limited by the compartment syndrome, can intercept RABV even after it gains access to the peripheral neural network where conventional post-exposure prophylaxis is ineffective and is cost-effective in the long term. The principle of physical alteration of vulnerable proteins by electricity delivered by electromagnetic radiation is not limited to RABV, but may be applied to a spectrum of viral pathogens.
post-exposure prophylaxis, Rabies, diathermy, magnetic field therapy, electric stimulation therapy, immunoglobulins, antiviral agents
Rabies is a dreadful disease with dramatic clinical course and almost 100% mortality. The causative agent is the Rabies virus (RABV), a bullet-shaped, enveloped, negative-sense RNA virus, 180 nm long and 60 nm wide. A genome of approximately 12,000 bp encodes five proteins: nucleoprotein N, polymerase L, phosphoprotein P, matrix protein M and glycoprotein G (
RABV is inoculated by a bite or scratch inflicted by an infectious animal. The virions move passively at the intercellular space with a pace of 12-24 mm/day and enter nerve cell axons through neuromuscular junctions or sensory terminals. While inside the neural network, the virions are inaccessible to antibodies. Subsequently, RABV is transported from peripheral nerves to the brain following a centripetal route. Once RABV reaches the brain, a progressive encephalitis occurs with an almost invariably fatal outcome (
In the majority of cases involving bite or scratch by an animal, only a theoretical risk assessment for RABV infection is possible. Animals appearing asymptomatic during the incident do not exclude transmission (
Often, even a remote theoretical risk of exposure to Rabies warrants the administration of post-exposure-prophylaxis (PEP) i.e. Rabies vaccine and, depending on type of exposure, Rabies immunoglobulin (RIG). According to WHO guidelines, RIG must be administered if the epidermis is penetrated (category III of exposure) (
Even though PEP is a crucial intervention for the prevention of infection, the Rabies vaccine and especially the RIG are often in short supply. Τhe topical infiltration of RIG at the site of trauma where it is highly effective (
The hyperthermia achieved by the diathermy physiotherapy devices (DPDs) in common physical therapy practice is due to the phenomenon of heat generation when electric current flows through a conductor (living tissues) according to Joule's and Ohm’s laws (Power = V2/R), where V is voltage and R is resistance (Joule effect) (
Inductive DPDs use a drum applicator (monode) where a rapidly oscillating (RF) electric current passes through a coil and a magnetic field is generated according to Maxwell’s laws of electromagnetism. The magnetic flux is driven by the monode to the target area and a reactive circular electric current is induced within the tissue, perpendicular to the magnetic lines (Eddy current) (Fig.
The principle of operation of the inductive physical diathermy devices. The alternating magnetic field generated by AC current induces a flow of electrons (Eddy current) perpendicular to the magnetic field. According to the hypothesis, the electrical phenomena can be exploited to adversely affect viruses in the targeted tissue. The topical hyperthermia occurs as the current passes through the ohmic resistance of the tissue and is not central to the hypothesis.
The magnetic field and the accompanying Eddy current reach deep tissues, without being hindered by skin, bones, tendons or other high-density structures. The local electric current is affected by factors such as wattage, frequency, tissue water content and distance from source (
The capacitive DPDs generate an oscillating electrostatic field in the RF range (shortwave or microwave frequencies) (
Inductive and capacitive DPDs distribute the electric current to the superficial and deeper tissues in a predictable pattern.
Both types of DPDs have two modes of application, the continuous mode and the pulse mode. The continuous mode is simply a non-stop RF emission towards the target, highly efficient for generating deep tissue heat. In the pulsed mode, RF is actively emitted during 'on' time (pulse) which is a fraction of the duration of the 'off' time and, therefore, the total energy delivered to the patient is relatively low, even though the peak power during the 'on' time can be quite high. The pulse has a typical duration of 20-400 microseconds and the pulses may range from 20-800 per second. Due to the less amount of delivered energy for the same time of application, the pulsed diathermy generates little or no heat and is preferred when the desired result is electric excitation rather than deep tissue heating (
Pulsed shortwave inductive DPDs offer an efficient delivery of the electric energy to the tissues with a minimal risk of thermal damage and the least safety concerns (
The central hypothesis is the application of electricity for the neutralisation of RABV and other Lyssaviruses as a replacement of RIG in post-exposure prophylaxis. The delivery of electric energy to the target tissue is achieved by repurposed shortwave or microwave diathermy physiotherapy devices (DPDs), commonly used in physical therapy. These devices accomplish hyperthermia by driving electric current through the ohmic resistance of the tissues (Ohm's law). The flow of ions is predictably distributed in a defined surface and depth of the targeted area unhindered by soft or hard anatomic structures. The rise of tissue temperature is a side effect of the electric phenomena and is not important in the present hypothesis. However, heat may exacerbate the bleeding of an open wound inflicted by animal and can even increase infectivity by enhancing local migration of virions. Therefore, the pulsed mode of DPD application is preferred over the continuous mode due to the negligible thermal effect (
RABV is surrounded by a host-derived lipid bilayer (envelope) acquired from the invaded cell during exocytosis. In general, enveloped viruses are considered more vulnerable to environmental stressors compared to non-enveloped viruses that are enclosed in a sturdy capsid (
The inductive DPDs generate a rapidly oscillating magnetic field that easily penetrates tissues. According to established Laws of Physics, a circular electric current is spontaneously formed, perpendicular to the magnetic lines occurring as a reaction at any change of the magnetic flux (“Eddy current”). Inductive shortwave pulsed output DPDs efficiently distribute the electric current within the treated tissue, exhibit a good safety profile and are proposed as the core diathermy devices. Fig.
Example of the proposed use of an induction diathermy physiotherapy device (A) to a victim bitten by a rabid animal at the gastrocnemius area. The alternating magnetic flux emitted by the drum applicator (B) generates Eddy current within the targeted tissue. A towel (C) is placed between the applicator and the subject to remove any superficial water (e.g. sweat, moisture) which could concentrate electric current and produce excessive localised heat. This setting could replace Rabies Immunoglobulin (RIG) in Rabies post-exposure prophylaxis.
The capacitive DPDs generate an oscillating electrostatic field between condenser electrodes placed close to the skin with the electric current flowing through the in-between tissue (Fig.
Electricity is known to adversely affect viruses. However, the direct application of electric voltage for therapeutic purposes on humans faces serious limitations. Human skin has tremendous impedance that may reach 100,000 ohms and can be penetrated only with high, lethal voltages when conventional electrodes are applied (e.g. naked wire). The current then flows at an unpredictable course through the path of the least impedance with a propensity to move along the periphery of human body (skin) rather than through the core (tissues) (
The virucidal effects of electric energy, mainly in the form of pulsed electric fields (PEF) of very high voltage for a very short time in food components and human-like cell substrates, have been previously described (
Recent studies have reported adverse effects of the electromagnetic radiation on SARS-COV-2;
The amino acids are acidic, basic, non-polar (hydrophobic) or polar (
RABV M and G proteins play a crucial synergistic role in cell invasion, virion intracellular formation and the release from the host-cell of the new viral particles by budding (
Common physiotherapeutic diathermy devices can be repurposed to neutralise RABV and replace the expensive and in short supply Rabies immunoglobulin. Apart from RABV, a wide range of pathogenic viruses may prove susceptible to the electric excitation induced by electromagnetism. The modality could be the precursor to a novel approach of combating viral infectious diseases by exploiting electric phenomena.
A preliminary theoretical assessment revealed that the application of electromagnetic energy for the deactivation of Rabies virus is possible and commonly used RF diathermy devices may potentially replace the conventional RIG. The diathermy physiotherapy devices have clearance for therapeutic applications on human patients, have been used for decades in rehabilitation and can distribute electric energy at various tissue depth. However, the incapacitation of the targeted viruses by inflicting sufficient damage to the viral proteins is only a theoretical postulate. The outcome is an equation of the electric energy applied at molecular level, the susceptibility of the protein domains and the impact of the protein alteration to the viral pathogenetic machinery. The experimental testing of the modality on cell cultures and laboratory animals can elucidate how the applied electric field affects the virus. We propose the application of pulsed-mode, shortwave, induction-type diathermy or a combination of induction and capacity-type devices for even better distribution of the electric current. If the laboratory cannot handle RABV due to safety constraints, other members of the Rhabdoviridae, for example, Vesiculovirus, a virus of low zoonotic potential affecting mainly livestock (
The benefits of the proposed modality as a RIG replacement include the significantly reduced expenses, the lack of anaphylaxis reaction, the equal protection against RABV and other Lyssaviruses, partially or not intercepted by the conventional PEP, such as the European Lyssaviruses (EBLV-1, EBLV-2), the Mokola virus (MOKV), the Lagos bat virus (LBV) and the West Caucasian bat virus (WCBV) (
Deleterious effects to other viral pathogens are possible as electrically sensitive proteinic components are not limited to RABV. Viruses localised in chronically-infected sites could be targeted with DPDs. For example, the dorsal ganglia and the liver could be targeted for Herpes simplex virus type 1 and Hepatitis C virus, respectively. The effectiveness of RF electric fields could be tried even in systemic viral infections via designs which deliver the emitted energy to large body areas or for prolonged periods. Enveloped viruses lack a durable protective capsid and might inherently be more vulnerable to the adverse effects of the electric current as some previous reports suggest that the non-enveloped viruses could be impervious to the flow of electric current (
The use of RF diathermy devices should be avoided on oedematous tissues, pregnant or menstruating women or bacterial septic infections, for example, tuberculosis (
The author is grateful to Mrs. Irini Eleftheriadou, professional painter and fine arts teacher, for her contribution to the artwork of this paper and her relentless support during the writing of this manuscript.
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Conceptualisation, methodology, writing-original draft preparation, revision, editing, visualisation, G.D.