Therapeutics

LITERATURE

COVID-19 Molecular Pathophysiology: Acetylation of Repurposing DrugsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated type 1 interferon (IFN-1) production, the pathophysiology of which involves sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) tetramerization and the cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway. As a result, type I interferonopathies are exacerbated. Aspirin inhibits cGAS-mediated signaling through cGAS acetylation. Acetylation contributes to cGAS activity control and activates IFN-1 production and nuclear factor-κB (NF-κB) signaling via STING. Aspirin and dapsone inhibit the activation of both IFN-1 and NF-κB by targeting cGAS. We define these as anticatalytic mechanisms. It is necessary to alleviate the pathologic course and take the lag time of the odds of achieving viral clearance by day 7 to coordinate innate or adaptive immune cell reactions.

코로나 치료제 시리즈 1

Jong Hoon, LEE. 코로나 사망자수를 줄여주는 아스피린: 코로나 치료제 시리즈 1. 2022. https://books.google.co.kr/books?id=E2ViEAAAQBAJ.

JONG Hoon, LEE. 코로나 호흡기질환을 예방치료하는 답손: 코로나 치료제 시리즈 2. 2022. https://books.google.co.kr/books?id=JOBiEAAAQBAJ.

Lee, J.H. 잠자는 나라 시리즈 3. 코비드-19 호흡부전 치료법: 천치와 수재가 코로나 바이러스를 만났을 때. 2021. https://books.google.co.kr/books?id=ESs_EAAAQBAJ.

항촉매치료에 대하여 - 코비드 19의 치료법

Lee, Jong-hoon, Ha Kyeu An, Mun-Gi Sohn, Paul Kivela, and Sangsuk Oh. "4,4′-Diaminodiphenyl Sulfone (Dds) as an Inflammasome Competitor." International Journal of Molecular Sciences 21, no. 17 (2020): 5953. https://www.mdpi.com/1422-0067/21/17/5953.

Kanwar, Badar, Chul Joong Lee, and Jong-Hoon Lee. "Specific Treatment Exists for Sars-Cov-2 Ards." Vaccines 9, no. 6 (2021): 635. https://www.mdpi.com/2076-393X/9/6/635.

Kanwar, Badar A., Asif Khattak, Jenny Balentine, Jong Hoon Lee, and Richard E. Kast. "Benefits of Using Dapsone in Patients Hospitalized with Covid-19." Vaccines 10, no. 2 (2022): 195. https://www.mdpi.com/2076-393X/10/2/195.

Khattak, Asif, Badar Kanwar, Consolato Sergi, Chul Joong Lee, Jenny Balentine, Jong-Hoon Lee, Jungwuk Park, So Jeong Lee, and Su-Hee Choi. "Commentary for the Elderly in the Pandemic Era." Dementia and Geriatric Cognitive Disorders Extra 11, no. 2 (2021): 168-71. https://doi.org/10.1159/000515926. https://www.karger.com/DOI/10.1159/000515926.

Lee, Jong Hoon, Badar Kanwar, Chul Joong Lee, Consolato Sergi, and Michael D. Coleman. "Dapsone Is an Anticatalysis for Alzheimer’s Disease Exacerbation." iScience (2022). https://doi.org/10.1016/j.isci.2022.104274. https://www.cell.com/iscience/fulltext/S2589-0042(22)00544-2.

Jong Hoon, L.EE. 코로나 호흡기바이러스 2형 질병 (Covid-19) 치료 기전. infomedpress, 2022. https://books.google.co.kr/books?id=1E96EAAAQBAJ.

Jong Hoon, LEE. 코로나 사망자수를 줄여주는 아스피린: 코로나 치료제 시리즈 1. 2022. https://books.google.co.kr/books?id=E2ViEAAAQBAJ.

JONG Hoon, LEE. 코로나 호흡기질환을 예방치료하는 답손: 코로나 치료제 시리즈 2. 2022. https://books.google.co.kr/books?id=JOBiEAAAQBAJ.

코로나 치료제 시리즈 2

진행하는 코비드 19 호흡부전 치료

- 코비드-19 치료 이해 (1)

Jong Hoon, L. E. (2022). 코로나 호흡기바이러스 2형 질병 (COVID-19) 치료 기전, infomedpress. https://books.google.co.kr/books?id=1E96EAAAQBAJ

- 코비드 19의 병리 이해 (2)

Jong Hoon, LEE. 코로나 호흡기바이러스 2형 질병 (Covid-19) 병리 기전: 코로나 병리를 알면 쉽게 예방 및 치료된다. infomedpress, 2022. https://books.google.co.kr/books?id=Hn13EAAAQBAJ.

발표 논문

4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome CompetitorThe aim of this study is to examine the use of an inflammasome competitor as a preventative agent. Coronaviruses have zoonotic potential due to the adaptability of their S protein to bind receptors of other species, most notably demonstrated by SARS-CoV. The binding of SARS-CoV-2 to TLR (Toll-like receptor) causes the release of pro-IL-1β, which is cleaved by caspase-1, followed by the formation and activation of the inflammasome, which is a mediator of lung inflammation, fever, and fibrosis. The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome is implicated in a variety of human diseases including Alzheimer’s disease (AD), prion diseases, type 2 diabetes, and numerous infectious diseases. By examining the use of 4,4′-diaminodiphenyl sulfone (DDS) in the treatment of patients with Hansen’s disease, also diagnosed as Alzheimer’s disease, this study demonstrates the diverse mechanisms involved in the activation of inflammasomes. TLRs, due to genetic polymorphisms, can alter the immune response to a wide variety of microbial ligands, including viruses. In particular, TLR2Arg677Trp was reported to be exclusively present in Korean patients with lepromatous leprosy (LL). Previously, mutation of the intracellular domain of TLR2 has demonstrated its role in determining the susceptibility to LL, though LL was successfully treated using a combination of DDS with rifampicin and clofazimine. Of the three tested antibiotics, DDS was effective in the molecular regulation of NLRP3 inflammasome activators that are important in mild cognitive impairment (MCI), Parkinson’s disease (PD), and AD. The specific targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by DDS may be responsible for its observed preventive effects, functioning as a competitor.

Specific Treatment Exists for SARS-CoV-2 ARDSThe COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seems to be difficult to overcome. A pandemic of such a scale has not been seen since the 1918 influenza pandemic. Although the predominant clinical presentation is respiratory disease, neurological manifestations and sequelae are increasingly being recognized. We observed a case series of rapid recovery of ARDS within 24 h in the preliminary clinical features of COVID-19 ARDS-associated neurological disease. It was also noted that by 15 April, 2021, there was no SARS-CoV-2 ARDS on Sorok Island in South Korea, where lepers had been living together. We compared each of dapsone’s effects on humans and considered those of SARS-CoV-2. Dapsone showed different effects in the brain. The Sorokdo National Hospital reported a relationship between dapsone and the neuroinflammasome of Alzheimer’s disease (AD) in Sorok Island from January 2005 to June 2020. AD prevalence was low in the leprosy patient group who took dapsone regularly. The preliminary cross-sectional study of the trial group (22 subjects) and the control group (22 subjects) in the Hunt Regional Hospital reported the following results: The chi-square statistic is 5.1836. The p-value is 0.022801. The result is considered significant at p < 0.05. The results from the medical treatment from 21 December to 29 December 2020 were considered. The mortality rates at the ARDS onset stage were 0% with dapsone administered as a standard COVID-19 treatment and 40% without dapsone administered as a standard COVID-19 treatment, respectively. Based on the respiratory failure and sudden high death rate originating from the involvement of the brainstem, especially the pre-Bötzinger complex, dapsone can be used to significantly reduce the incidence of the cases of acute respiratory distress syndrome and other illnesses caused by SARS-CoV-2.

Benefits of Using Dapsone in Patients Hospitalized with COVID-19Since the start of the SARS-CoV-2 pandemic, refractory and relentless hypoxia as a consequence of exuberant lung inflammation and parenchymal damage remains the main cause of death. We have earlier reported results of the addition of dapsone in this population to the standard of care. We now report a further chart review of discharge outcomes among patients hospitalized for COVID-19. The 2 × 2 table analysis showed a lower risk of death or discharge to LTAC (Long term acute care) (RR = 0.52, 95% CI: 0.32 to 0.84) and a higher chance of discharge home (RR = 2.7, 95% CI: 1.2 to 5.9) among patients receiving dapsone compared to those receiving the usual standard of care. A larger, blinded randomized trial should be carried out urgently to determine if dapsone indeed improves outcomes in COVID-19.

RCT study

Critical Care Results of SARS-CoV-2 ARDS by Dapsone and Standard COVID-19 Treatment - Full Text View - ClinicalTrials.govCritical Care Results of SARS-CoV-2 ARDS by Dapsone and Standard COVID-19 Treatment - Full Text View.

Dapsone Coronavirus SARS-CoV-2 Trial (DAP-CORONA) COVID-19 - Full Text View - ClinicalTrials.govDapsone Coronavirus SARS-CoV-2 Trial (DAP-CORONA) COVID-19 - Full Text View.