Coronaviruses are large, roughly spherical particles with bulbous surface projections. The average diameter of the virus particles is around ۱۲۵ nm (.۱۲۵ μm). The diameter of the envelope is ۸۵ nm and the spikes are ۲۰ nm long. The envelope of the virus in electron micrographs appears as a distinct pair of electron-dense shells (shells that are relatively opaque to the electron beam used to scan the virus particle).
The viral envelope consists of a lipid bilayer, in which the membrane (M), envelope (E) and spike (S) structural proteins are anchored. The ratio of E:S:M in the lipid bilayer is approximately ۱:۲۰:۳۰۰. On average a coronavirus particle has ۷۴ surface spikes. A subset of coronaviruses (specifically the members of betacoronavirus subgroup A) also have a shorter spike-like surface protein called hemagglutinin esterase (HE).
The coronavirus surface spikes are homotrimers of the S protein, which is composed of an S۱ and S۲ subunit. The homotrimeric S protein is a class I fusion protein which mediates the receptor binding and membrane fusion between the virus and host cell. The S۱ subunit forms the head of the spike and has the receptor binding domain (RBD). The S۲ subunit forms the stem which anchors the spike in the viral envelope and on protease activation enables fusion. The E and M protein are important in forming the viral envelope and maintaining its structural shape. Inside the envelope, there is the nucleocapsid, which is formed from multiple copies of the nucleocapsid (N) protein, which are bound to the positive-sense single-stranded RNA genome in a continuous beads-on-a-string type conformation. The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host cell.
Cold Plasma Componds:
The efficacy of Cold plasma (CP) is due to its many components that exhibit favorable behavior for biomedical applications, including electrons, charged particles, reactive oxygen species (ROS), reactive nitrogen species (RNS), free radicals, ultraviolet (UV) photons, molecules, electromagnetic fields, physical forces, and electric fields.
Most notably, CP has been applied to applications such as sterilization, wound healing, coagulation, skin diseases, cancer therapy, immunotherapy, and regenerative medicine.
Potential mechanisms for CP action on COVID-۱۹ leading to loss of functionality and sterilization are showed in above picture. The COVID-۱۹ outbreak has led to dangerous shortages of sterilization capacity at hospitals, businesses, and in homes. Sterilization by CP is an alternative to conventional and/or traditional sterilization methods. CP sterilization is caused by plasma-generated reactive species inducing virus leakage and functionality loss. The levels of these reactive species can be adjusted by plasma source design (e.g., electrode orientation and gas feed mechanism), feeding gas types, operating conditions (e.g., electrode voltages and gas flow rates), the nature of the product/substrate, and the micro-organism itself. Studies highlighted the breakage of structurally important bonds, such as C-C, C-O, and C-N. Further, intracellular pH may be lowered by CP generated ROS and RNS, as shown in Fig. diffusing into the virus, inactivating it due to the absence of pH homoeostasis. Mass transport through the membrane becomes dysregulated by oxidative damage to membrane lipids. Separately, charged particle accumulating on the virus’ surface also damages cell membrane through electrostatic disruption. The electrostatic forces from such an accumulation can exceed the tensile strength of the membrane, leading to its rupture. ROS also play a part in membrane disruption, as they can drive protein denaturation and virus leakage. Such reactive species can induce oxidation of amino acids, nucleic acids, and unsaturated fatty acid peroxides through interaction with membrane lipids, leading to changes in the membranes’ function. Nucleic acids oxidized to ۸-hydroxy-۲ deoxyguanosine and amino acids oxidized to ۲-oxo-histidine. Changes in the membrane directly affect the nucleoid primarily via pore formation and breakdown of the interactions between nucleoid and membrane proteins. In addition, several other mechanisms for antimicrobial effects also exist, including other reactive atoms and ions, emissions (UV), electrons, metastable, and electronically/vibrationally excited molecules. Mechanisms for addressing COVID-۱۹ are driven by the ability of CP treatment to contribute to virus death including etching virus walls, damaging virus membranes, destruction of genetic materials, and protein/enzyme denaturation, as shown in belove
The importance of primary infection control measures have been highlighted for COVID-۱۹. Clean hands frequently with alcohol-based hand rub or soap and water has been cited by the WHO as being “one of the most important hygiene measures in preventing the spread of infection”. Hands are one of the most frequent transmission routes for many infections because they come in direct contact with known portals of entry for pathogens, such as mouth, nose, and eyes. Recently, CP activated medium (liquid) has increasingly be shown as an important approach in the field of plasma biomedicine. Free radicals and reactive species generated in the atmosphere and at the plasma-medium interface can penetrate side interfaces and enter the so-called “bulk medium” to react or recombine, giving rise to the generation of more stable ROS and RNS (such as H۲O۲, NO۲). ROS and RNS concentrations in He CP treatment culture medium show timedependent behavior, as shown in Fig. (a). air CP treated DI water resulting into pH value decreasing, as shown in Fig. (b). According to the Centers for Disease Control (CDC), H۲O۲ is a stable and effective disinfectant against viruses. Thus, CP-activated medium can be used as hand sanitizer to prevent the infection transmission of COVID-۱۹. COVID-۱۹ virus inactivation by CP-activated mudium results from the combined action of a low pH and a high positive oxidation reduction potential. CP-activated mudium can also kill active COVID-۱۹ virus on medical PPE, surfaces, instruments, etc. Such a CP-based mudium will be of extreme value, processing the functions of sterilizing/disinfection everywhere, such as at home, in the office, public spaces, at entrances of buildings, in hospitals, and in laboratories. This technology can avoid the need for sanitizers that require consumables such as alcohol and are thus susceptible to supply chain disruption. Another important component of CP is nitric oxide (NO). NO is a gas that enables diverse biological activities, and can interact with superoxide (O۲-), forming peroxynitrite (ONOO-) to mediate bactericidal or cytotoxic reactions in turn. Moreover, NO has played a major role in regulating airway function and in treating inflammatory airway diseases. The beneficial effects of NO inhalation is observed in most patients with severe ARDS (acute respiratory distress syndrome) since it impedes the synthesis of viral protein and RNA. In addition, organic NO donor, Snitroso‐N‐acetyl penicillamine, can remarkably obstruct the replication cycle of SARS-CoV. Thus, the NO inhalation can be potential for the treatment of severe COVID-۱۹. Additionally, NO collides with O۲ – to ONOO- being one of important cytotoxic reactions in plasma cancer therapy. Generally, NO is most prominent for CP devices that use helium as a supplemental feeding gas. Operators can adjust concentration of NO through changing feeding gas types (nitrogen or mixed gas), operating conditions, and so on. In this way, CP is one of best sources for controllable NO that can treat severe COVID-۱۹ infected patients.
To better survive in host cells, SARS-CoV-۲ employs multiple strategies to avoid immune responses. COVID-۱۹-infected pneumonia patients typically have severe immune abnormalities and risk of cytokine release syndrome (CRS), which results into a decrease of T cells and Natural Killer (NK) cells and an increase of interleukin ۶ (IL-۶), CD۴/CD۸ ratio (CD: cluster of differentiation), fever, tissue/organ dysfunction, and an abnormal coagulation function. Currently, immunotherapy has been proved to an effective treatment to fight COVID-۱۹ infections. The potential mechanism is that inflammatory cells, such as effector T cells and macrophages, accumulate rapidly from peripheral blood by chemokines and release a large number of cytokines into the blood when they kill tumor cells, viruses, or bacteria. Stem cells are hardwired to express antiviral interferon-stimulated genes. In addition, β-glucan is capable of training both hematopoietic stem cell (HSCs) and myeloid progenitors. These conditioned HSCs and myeloid progenitors can more efficiently ward off inflammatory challenges. CP treatment promotes dendritic cell (DC) maturation in the lymph node, where DCs can present the major histocompatibility complexpeptide to T cells. The subsequent T cell-mediated immune response can be augmented by the immune checkpoint inhibitors, resulting in enhanced local and systemic antiviral immunity. The adoptive therapy of CP should be an ideal choice to be employed or combined with other immune modulating agents for COVID-۱۹.
Although the trajectory of COVID-۱۹ outbreak is impossible to predict, timely development and implementation of effective countermeasures are necessary. CP is an alternative to conventional and/or traditional sterilization and treatment methods for COVID-۱۹ due to its causing virus leakage and functionality. Specifically, CP-activated liquid, containing H۲O۲ and exhibiting low pH, is able to kill active COVID-۱۹ virus on hands, medical PPE, surfaces, etc. This prevents the transmission of infection further causing several diseases such as COVID-۱۹, nosocomial food-borne illness, and others. CP generating NO can treat severe COVID-۱۹ infected patients. Moreover, CP immunotherapy is an effective treatment to fight COVID-۱۹ infections because it can increase T cells and NK cells to normal levels and recover tissue/organ from dysfunction and coagulation function from abnormal. Until now, there are still no specific antiviral medications approved for COVID-۱۹, however, development efforts are underway. In parallel and during this process, CP can make its own important contributions to COVID-۱۹ challenges. In summary, CP has great potential for preventing the transmission of COVID-۱۹ infections and treating severely infected COVID-۱۹ patients