The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had caused over 382 million cases and over 2.7 million deaths globally as of 23 March 2021. By ...The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had caused over 382 million cases and over 2.7 million deaths globally as of 23 March 2021. By that date, at least 10 SARS-CoV-2 variants had emerged. The transmissibility and lethality of the variants are higher than those of the Wuhan reference strain. Therefore, a universal vaccine for the reference strain and all variants (present and future) is indispensable. The coronavirus envelope (E) protein is an integral membrane protein crucial to the viral lifecycle and the pathogenesis of coronaviruses. The SARS-CoV-2 E protein has a postsynaptic density protein 95/Drosophila disc large tumor suppressor/zonula occludens-1 (PDZ) binding motif (PBM), and its interaction with PDZ-domain-2 of the human tight junction protein may interrupt the integrity of lung epithelium. Furthermore, the SARS-CoV-2 E protein itself is a homopentameric cation channel viroporin, which may be involved in viral release. This protein is thus a potential target for the development of a universal COVID-19 vaccine, because of its highly conserved amino acid sequence. The variant mutations occur mainly in the spike protein, and conservation of E protein remained in most Variants of Concern (VOC). Only one of the extant VOC have mutations in the E protein that P71L mutation occurs in the South African variant 501Y.V2 (B.1.351). If a vaccine is designed to target E protein, two scenarios are possible: 1) SARS-CoV-2 maintains a highly conserved E protein amino acid sequence, rendering the virus consistently or permanently susceptible to the vaccine;or 2) the E protein mutates and new variants evolve accordingly. In scenario 2, the tertiary structure and function of the E protein homopentameric cation channel viroporin, PBM, or other aspects affecting pathogenicity would be attenuated. Either scenario would thus ameliorate the pandemic. I therefore propose that a vaccine targeting the SARS-CoV-2 E protein would be effective against the Wuhan reference strain and all current and future SARS-CoV-2 variants. Efforts to create E protein-based vaccines are ongoing. Further research and clinical trials are needed to realize this universal COVID-19 vaccine.展开更多
General anesthesia relies on pharmacological anesthetics. However, some side effects of anesthetics have been observed. Non-pharmacological transcranial photobiomodulation (tPBM) as an adjuvant treatment may reduce th...General anesthesia relies on pharmacological anesthetics. However, some side effects of anesthetics have been observed. Non-pharmacological transcranial photobiomodulation (tPBM) as an adjuvant treatment may reduce the dosage of pharmacological anesthetics while maintaining anesthetic depth. The inhibitory effects of tPBM in terms of central nervous system depression render it a potential approach for inducing general anesthesia. Alteration of quantum processes of neuronal microtubules, the mechanisms of general anesthesia on consciousness, may occur in response to tPBM treatments. Further, tPBM as an adjuvant treatment may facilitate the distribution of the pharmacological anesthetics in the brain. The analgesic effects of photobiomodulation (PBM) are acknowledged, and PBM has been used for regional analgesia. However, whether tPBM can be used for general anesthesia is unknown. Here, I define “optoanesthesia” as “the use of tPBM for general anesthesia”. I hypothesize that optoanesthesia can act as a means of general anesthesia. Supporting evidence in the form of unconsciousness, amnesia, and immobilization is provided in this paper. In addition, the tPBM-induced frequent yawning (a manifestation of transient arousal-shift during the continuing loss of consciousness during induction of general anesthesia) observed incidentally in my previous study of tPBM preconditioning for seizures also supports the hypothesis. I further discuss the issues with respect to the pharmacokinetics, parameters of optoanesthesia such as wavelength and targeted brain regions, and apparatus design, as well as the compatibility of the optoanesthesia and the Bispectral Index Monitoring System during surgery. Future research is needed to prove this hypothesis.展开更多
文摘The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had caused over 382 million cases and over 2.7 million deaths globally as of 23 March 2021. By that date, at least 10 SARS-CoV-2 variants had emerged. The transmissibility and lethality of the variants are higher than those of the Wuhan reference strain. Therefore, a universal vaccine for the reference strain and all variants (present and future) is indispensable. The coronavirus envelope (E) protein is an integral membrane protein crucial to the viral lifecycle and the pathogenesis of coronaviruses. The SARS-CoV-2 E protein has a postsynaptic density protein 95/Drosophila disc large tumor suppressor/zonula occludens-1 (PDZ) binding motif (PBM), and its interaction with PDZ-domain-2 of the human tight junction protein may interrupt the integrity of lung epithelium. Furthermore, the SARS-CoV-2 E protein itself is a homopentameric cation channel viroporin, which may be involved in viral release. This protein is thus a potential target for the development of a universal COVID-19 vaccine, because of its highly conserved amino acid sequence. The variant mutations occur mainly in the spike protein, and conservation of E protein remained in most Variants of Concern (VOC). Only one of the extant VOC have mutations in the E protein that P71L mutation occurs in the South African variant 501Y.V2 (B.1.351). If a vaccine is designed to target E protein, two scenarios are possible: 1) SARS-CoV-2 maintains a highly conserved E protein amino acid sequence, rendering the virus consistently or permanently susceptible to the vaccine;or 2) the E protein mutates and new variants evolve accordingly. In scenario 2, the tertiary structure and function of the E protein homopentameric cation channel viroporin, PBM, or other aspects affecting pathogenicity would be attenuated. Either scenario would thus ameliorate the pandemic. I therefore propose that a vaccine targeting the SARS-CoV-2 E protein would be effective against the Wuhan reference strain and all current and future SARS-CoV-2 variants. Efforts to create E protein-based vaccines are ongoing. Further research and clinical trials are needed to realize this universal COVID-19 vaccine.
文摘General anesthesia relies on pharmacological anesthetics. However, some side effects of anesthetics have been observed. Non-pharmacological transcranial photobiomodulation (tPBM) as an adjuvant treatment may reduce the dosage of pharmacological anesthetics while maintaining anesthetic depth. The inhibitory effects of tPBM in terms of central nervous system depression render it a potential approach for inducing general anesthesia. Alteration of quantum processes of neuronal microtubules, the mechanisms of general anesthesia on consciousness, may occur in response to tPBM treatments. Further, tPBM as an adjuvant treatment may facilitate the distribution of the pharmacological anesthetics in the brain. The analgesic effects of photobiomodulation (PBM) are acknowledged, and PBM has been used for regional analgesia. However, whether tPBM can be used for general anesthesia is unknown. Here, I define “optoanesthesia” as “the use of tPBM for general anesthesia”. I hypothesize that optoanesthesia can act as a means of general anesthesia. Supporting evidence in the form of unconsciousness, amnesia, and immobilization is provided in this paper. In addition, the tPBM-induced frequent yawning (a manifestation of transient arousal-shift during the continuing loss of consciousness during induction of general anesthesia) observed incidentally in my previous study of tPBM preconditioning for seizures also supports the hypothesis. I further discuss the issues with respect to the pharmacokinetics, parameters of optoanesthesia such as wavelength and targeted brain regions, and apparatus design, as well as the compatibility of the optoanesthesia and the Bispectral Index Monitoring System during surgery. Future research is needed to prove this hypothesis.
