Some Measures for COVID-19 Including Deep Ultraviolet Light-Emitting Diode (DUV-LED), Gc protein-derived Macrophage-Activating Factor (Gcmaf), and 5-Aminolevulinic Acid (5-ALA)

Citation: Bando H. Some Measures for COVID-19 Including Deep Ultraviolet Light-Emitting Diode (DUV-LED), Gc protein-derived Macrophage-Activating Factor (Gcmaf), and 5-Aminolevulinic Acid (5-ALA). Asp Biomed Clin the any medium provided the original work is properly cited. Abstract Several trials for the COVID-19 pandemic are found. Prof. Nakamura, University was awarded the 2014 Nobel prize in Physics for light-emitting diodes (LEDs). Deep ultraviolet LED (DUV-LED) causes SARS-CoV-2 inactivation as 99.9% by 265 nm. Gc protein-derived macrophage-activating factor (GcMAF)-based immunotherapy has a wider application for serious infection, chronic fatigue syndrome, and cancers. Covid center in Naples submitted a phase II report concerning GcMAF and COVID-19 in Feb 2021. 5-aminolevulinic acid (5-ALA) and its metabolite protoporphyrin IX (PpIX) show anti-inflammatory and antiviral effects for Zika, Dengue, influenza A viruses, and SARS-CoV-2. These results hopefully contribute to the research development for COVID-19.

diodes (LDs) was achieved by Prof. Shunji Nakamura, Tokushima University. He was awarded the 2014 Nobel prize in Physics [5]. Using this deep ultraviolet light-emitting diode (DUV-LED), quantitative evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivation was reported as 99.9% in 2021 [6]. For the achievement of this level, total doses of 1.8 mJ/cm 2 for 265 nm, 3.0 mJ/cm 2 for 280 nm, and 23 mJ/cm 2 for 300 nm are required. These data could provide the quantitative antiviral clinical efficacy by DUV irradiation on SARS-COV-2, which serves the fundamental knowledge of inactivation methods for SARS-COV-2. This project was supported by Tokushima Prefectural Government and Tokushima University. According to the data mentioned above, some experiments were conducted using LEDs systems by changing the condition [7]. As a result, a wavelength of 260 nm was most effective for the inactivation of coronavirus particles. This research will be expected to develop for broad application worldwide.
Another international research has been found. Clinical research for Gc protein-derived macrophageactivating factor (GcMAF) has been continued in Tokushima University for years [8]. GcMAF has a variety of functions as an immune modulator, including macrophage activation, anti-tumor activity, and anti-angiogenic activity. Consequently, GcMAFbased immunotherapy shows a wider application for serious infection, chronic fatigue syndrome, multiple sclerosis, and several cancers [9]. GcMAF has the possibility of the role for suppressing the severity of COVID-19-induced immune responses [10]. Covid center in Naples, Italy summarized the phase II report concerning GcMAF and COVID-19 pneumonia with 104 references and 63 pages in Feb 2021 [11]. Further development for the interaction of GcMAF and COVID-19 will be expected.
The third topic is 5-aminolevulinic acid (5-ALA). The research group of Tokushima University formerly reported the involvement of 5-ALA, which is the precursor of protoporphyrin IX (PpIX) for the possible sonosensitizers for sonodynamic treatment of cancers [12]. 5-ALA is a synthesized amino acid and has been applied for various purposes such as anticancer therapy or as a dietary supplement. Recently, it has been showed potently inhibition of infection of SARS-CoV-2 in cell culture. The detailed research has been continued at Nagasaki University in Japan [13]. Its antiviral efficacy was detected in both human and nonhuman cells with no significant cytotoxicity. 5-ALA is one of the natural amino acids and exists in plants, bacteria, fungi, and animals. The conjugation of 8 molecules of 5-ALA bring the production of PPIX, which can generate heme with the ferrous ion insertion. Since 5-ALA strengthens the aerobic energy metabolism, it is applied for improved metabolism in such as diabetes mellitus [14]. Its application was broadened for infections such as malaria [15]. Furthermore, PPIX was known to show antiviral efficacy for various viruses including Zika virus, Dengue virus, influenza A virus, and also SARS-CoV-2 [16].
It has been reported that exogenously supplied 5-ALA affects the host through various mechanisms [17]. Metabolites of 5-ALA such as PPIX and hem seem to affect viral infection existing inside the host cells. A recent report demonstrated that a G-quadruplex (G4)binding compound could inhibit SARS-CoV-2 replication [18]. G4s show tetra-helical structures made of guanine-rich regions of DNA or RNA, which can regulate gene expression, genome stability, and adequate control of protein quality [19]. G4 structures have been observed in the genome of many kinds of viruses such as coronaviruses and can regulate viral replication cycles. As to recent studies, G4 structures of the SARS-CoV-2 RNA genome and its interaction with the binding proteins would become possibly antiviral targets to attach COVID-19 [18,20]. In addition, heme is the metabolites of 5-ALA and a ligand of G4 structures [21]. Consequently, exogenous 5-ALA administration leads to increased production of PPIX and heme inside the host cells, which may interfere with the interaction of G4 structures or virus genome leading to inhibition of SARS-CoV-2 infection.
5-ALA is synthesized in most plants and animals, and then we always consume it within our daily foods [22]. Then, it is safely provided to humans as a supplement or medicine for a wider population including mild cases of patients with COVID-19 [23]. Moreover, 5-ALA shows anti-inflammatory efficacy in humans, and then it is possible to provide rather severe cases for the combined therapy for antiinflammation and antiviral activity [22]. Concerning the research of 5-ALA and COVID-19, experiments using swine have been found [24,25]. Consequently, further studies of antiviral function by animal experiments and mechanistic research will be expected.
As mentioned above, several recent topics were introduced and discussed in this article. They include i) SARS-CoV-2 inactivation was 99.9% by DUV-LED, ii) GcMAF would be effective as phase II report from Italy, iii) 5-ALA would be applied for COVID-19. The information will be hopefully prevalent across the world rapidly, leading to the health and happiness of all people with the development of research of COVID-19.

Conflict of Interest
The author has read and approved the final version of the manuscript. The author has no conflicts of interest to declare.