羥氯喹(HCQ)是繼青黴素之後的第二次醫學科學大革命嗎?

作者:葉寧

人氣 2537

【大紀元2020年12月23日訊】撰寫此手稿是旨在拯救Covid-19流行病患者生命的緊迫壓力下促成。

新冠病毒綜合徵自2020年2月以來已奪走了50多萬美國人的生命,這很可能是由於實際上缺乏正確的治療方法所致。我不是專業的病毒學家/流行病學家。憑藉中國傳統草藥的家庭背景,我擁有豐富的學習經驗,在業餘時間關注世界上不斷改進的生產和專注於該藥物的最新方法論相互比較驗證,並經常和在醫學科學領域位居前茅的卓越科學家進行徹夜長談之後發現了羥氯喹的巨大抗病毒作用。美國國立衛生研究院是世界上擁有數量最多的著名頂尖生命科學家的總部,代表著最前沿的生命科學發展巔峰。我在那裡收益甚豐。

自2020年1月以來,我向中國大陸貢獻了5個Covid-19替代療法,其中包括熱檸檬薑茶,以及逆轉人體蛋白質缺乏和過度疲勞的方法。作為得到部分接受的方法論指南,其目的僅僅是為了挽救生命於毀滅性的Covid大流行。在最黑暗的時期開始時,促使我參與人道主義行動以挽救Covid-19病人生命的主要原因是,我對在中國武漢拍攝到的錄像感到震驚,很多人在街上倒地而死。有人深感恐懼竟然從高層公寓樓的窗戶跳下自殺。 「您不必死於像冠狀病毒感染綜合徵那樣的疾病!」。不幸的是,預測美國的轉折點應該在2020年5月出現失敗了。因為唐納德·特朗普總統大膽的羥氯喹倡導在4月份遭到偽證挫敗。隨後FDA撤銷了頒發給羥氯喹的臨時「臨床試驗」許可。死亡率隨後迅速攀升。全國各地醫院的Covid-19傷亡人數急劇上升。我為羥氯喹在美國紐約南區地方法院(20-3067-RA)尋求Mandamus令狀而進行的法律鬥爭並未帶來迅速而積極的結果。現在,由於所有非醫學方面干擾羥氯喹當作治療過濾性慢病毒流行病的合力在大選後逐漸消失,今天應該是大家一心來專注於這一挽救生命的崇高事業的時候了。

  1. HCQ的發現及其抗病毒作用

氯喹(CQ)是一種9-氨基喹啉,於1934年被發現。羥氯喹(HCQ)是一種具有更強治療效果的先進CQ類型,是基於神諭在中國開始的臨床試驗中海選出來的一種古老藥物,已被使用。與致命的大流行瘟疫作鬥爭。羥氯喹之前,還沒有有效的藥物來治療由Flu到Covid-19甚至AIDS這類濾過性慢病毒引起的各種傳染病的有效化學配方。已經表明,羥氯喹(HCQ)對流感病毒SARS-CoV和SARS-CoV2及其變異分枝Covid-19病毒感染靈長類動物細胞的濾過性慢病毒具有顯效能以此進行有效的治療。人類首次發現羥氯喹(HCQ)對廣譜濾過性慢病毒病毒具有抑制作用和較低/極微弱毒副作用的治療效果。對病毒性流感和新冠綜合徵具有極強的抗病毒作用。此外,臨床試驗證明,每天接受200-600mg 羥氯喹(HCQ)劑量的每個成員三到五天治療期間顯示出幾乎接近100%的康復結果。對於急性流感患者,小劑量服藥一到三次,症狀全部消失。

  1. HCQ治療Covid-19的臨床評價

嚴重急性呼吸系統綜合症(SARS)及其新類型變異Covid-19,是由新發現的冠狀病毒SARS-CoV2引起的。 Covid-19是一種新興疾病,於2019年末在中國湖北省首次報道。該疾病迅速傳播到整個世界,對美國造成了最嚴重的影響,Covid-19相關的死亡人數已達到六位數,全球範圍內的努力因非醫學併發症(這對人類而言非常不幸)而失敗,未能鑑定出冠狀病毒科(冠狀病毒科的新成員)的病原體冠狀病毒,再加上未能找到和鑑定最有效和可用的治療與醫學無關的併發症的藥物成為藉口。2005年之前,確實沒有有效的預防或暴露後的治療方法。

值得注意的是,據報道,每天服用400-800毫克羥氯喹治療Covid-19併發症前患者獲得100%的清除率和奇蹟結果,所有病毒均被消除。(1) Vladimir Zelenko博士和其他人使用他的HCQ-基於雞尾酒的雞尾酒已經在臨床試驗中成功治療了數百名Covid-19患者,他最近預測,從英國傳播的Covid-19病毒的新變種也在羥氯喹HCQ治療區範圍之內。(2)(今年三月初鍾南山院士在全國醫學科學連線會議宣布磷酸氯奎對治療早期新冠具有顯效。)

此外,在使用羥氯喹HCQ治療Covid-19患者的臨床試驗中,有一些失敗或不足的報道。這種零星的故障被用來惡意攻擊羥氯喹HCQ。未公開的原因可能是由於劑量不足或為時已晚。Vladimir Zelenko博士的不足在於並非在所有Covid-19病例中都必須千篇一律的雞尾酒療法。對於沒有發現細菌感染或炎症的早期Covid-19患者,是不需要抗生素更不需要大劑量抗生素的。但是,對於已經歷Covid-19病毒觸發的非病毒性併發症的晚期患者,單純使用羥氯喹HCQ則為時已晚。在後期,該過程需要支持性對症治療,例如抗生素,抗炎,抗血栓形成/抗凝血和/或降低自身免疫性風暴療法,也可謹慎地使用後遺症嚴重的萬金油激素療法。另外,如瑞典的經驗所示,抗生素過量也會造成嚴重後果,因此必須採取預防措施。

  1. 羥氯喹HCQ極為低毒

改良的羥氯喹HCQ配方已被廣泛用於治療人類疾病,例如瘧疾,阿米巴病,HIV,狼瘡和自身免疫性細胞因子風暴,而沒有明顯有害的副作用,即使對於孕婦也絕對安全。儘管這種效果似乎比大多數(如果不是全部)FDA批准的用於治療癌症患者的化療藥物不知道要安全多少倍。儘管在大多數文明國家的《藥物規範》中早就包含了這種化學療法的指南。但是,最近還是對羥氯喹服用後的安全性和毒副作用做了持續一年之久的雙盲臨床實驗。美國國立衛生研究院相關診所於2012年3月至2013年3月對103例狼瘡患者進行了一項觀察羥氯喹HCQ安全性的臨床試驗。對照組每個成員每日HCQ 200-400 mg的劑量,累積總量高達144000毫克。沒有,重複一遍,羥氯喹HCQ服用組中沒有任何人遭受任何可見的副作用。(3)太安全了。

羥氯喹HCQ的分子「重量」為434(433.96)單位。體外有效消除顯示10μM 氯喹CQ或5μM 羥氯喹HCQ,消除了100%的廣譜過濾慢病毒。在通過數學模型考慮了所有可能的降解率之後,治癒Covid-19早期患者或Flu患者的平均劑量應為2.17 mg / kg體重。對於Covid-19中晚期患者,應該增加劑量為為6.21 mg / kg體重。因此,每日劑量200-600mg口服就足夠了。一週劑量將有效地消除幾乎所有病毒感染並消除體內病毒。由於羥氯喹HCQ表現出極低的毒性,因此如果臨床劑量每天增加至400-800 mg,則在臨床試驗中短時間(例如,連續處方少於6個月)不會產生任何具有統計意義的毒副作用。對於相對超重的患者,前兩天口服劑量為800毫克,不會引起毒性反應。

  1. CQ氯喹和羥氯喹HCQ的感染前和感染後效果

羥氯喹HCQ可以全面有效地預防細胞培養中從急性流感到Covid-19和SARS等濾過性慢病毒的傳播。在實驗室的體外實驗和中國的體內臨床試驗中,當在過濾慢病毒感染之前或之後用HCQ處理細胞時,均觀察到了良好的病毒傳播抑制作用[1]。

最近,Vincent等人報道在Vero E6細胞中用0.1μMCQ或0.05μMHCQ進行預處理可將感染率降低28%,而將10μM 氯喹CQ或5μM 羥氯喹HCQ進行預處理可將感染率降低100%(圖1).1

該研究還評估了病毒吸附後氯喹CQ的即時作用,他們發現在病毒吸附後3和5 小時加入氯喹可以有效地清除感染的病毒(圖2)。1電子顯微鏡分析表明,在5-6 h內出現了大量的細胞外病毒顆粒4這些數據表明,用氯喹CQ預處理Vero E6細胞使這些細胞難以抵抗SARS-CoV感染,感染後給予氯喹CQ顯示出明顯治癒作用。

圖2.定時用氯喹進行感染後治療。

4.2 羥氯喹HCQ阻止了Covid-19與刺突糖蛋白的結合

當在細胞外添加氯喹時,氯喹CQ的非質子化部分進入細胞,在那裡質子化並濃縮在酸性,低pH的細胞器中,例如內體,高爾基囊泡和溶酶體。 氯喹CQ可以多種方式影響病毒感染,抗病毒作用部分取決於病毒利用內體進入的程度。除了羥氯喹HCQ的眾所周知的功能(例如提高內體pH平衡)外,該藥物似乎還干擾了細胞受體血管緊張素轉換酶2ACE2)的末端糖基化。這可能會對病毒受體的結合產生阻抗等負面影響並消除感染,並因水泡pH值的升高而產生進一步的治療後果,從而在臨床允許的濃度範圍內對流感綜合徵,SARS CoV和Covid-19的感染和傳播產生全面和奇蹟般的抑制作用。已經被中國各地醫院的臨床試驗證明其顯效。(在美國何嘗不是呢?)

在人類八十多年的抗病毒藥物研究中,生命科學家們長期以來一直致力於阻止病毒劍突糖蛋白(類似於信號輸出天線)與宿主細胞的ACE2受體之間的連接附著,以消除與細胞受體的病毒結合,從而遏制引發病毒感染。這種研究思路一以貫之,長達八十多年幾乎沒有進展。以Covid-19和Sars為例,SARS-CoV的出芽發生在高爾基體中,並導致包膜刺突糖蛋白摻入到病毒體中。刺突糖蛋白是一種I型膜蛋白,可促進病毒附著於細胞受體並引發感染,血管緊張素轉換酶2(ACE2)已被鑑定為這種過濾性慢病毒(包括SARS-CoV和Covid)的功能性細胞受體。Vincent等人最近發現,刺突蛋白的加工受到弗林蛋白酶樣轉化酶的影響,並且特定抑制劑對這種裂解的抑制作用消除了細胞病變,並顯著降低了病毒效價(圖3)。相反, 羥氯喹HCQ的抗病毒作用可能不是由於病毒糖蛋白生物合成和加工過程的改變。(1)與之前的分析一致,(1)他們觀察到了較大蛋白質的存在,在這裡被稱為寡聚物。最近,Song女士等研究者提供的證據表明這些是SARS-CoV穗蛋白的同源三聚體,並已摻入病毒體中。

圖3.溶智劑對ACE2在細胞表面表達和生物合成的影響。

羥氯喹HCQ在Covid-19治療中的未來臨床應用

疫苗,特別是mRNA類疫苗,屬於體內免疫系統增強作用類,其改變人類基因的潛在因素不可忽視,且跟不上病毒突變速度。自行車趕飛彈。疫苗不是直接用來消除病毒的化學殺毒劑殺手,當羥氯喹HCQ密度達到10 MU時,體外可100%消除病毒。對於這種代際突變過快的病毒(例如Covid-19),疫苗的開發速度是否可以與該代際突變相匹配,並且毒性評估可能還不清楚。羥氯喹已被證明是有效的或什至是全效的,在體內沒有或幾乎沒有毒性副作用。今天,我們見證了由羥氯喹HCQ領導的具有里程碑意義的轉折點,它是一種經過驗證的有效的廣譜抗病毒劑,幾乎沒有毒性的副作用,這為Lord帶來了「 Great Grace好消息」,從而挽救了成千上萬的大流行病毒患者的生命。一場開創性的醫學革命,就像發現青黴素以消除八十年前的各種致死細菌一樣,開始了。新冠綜合徵對人類的另類貢獻巨大,儘管代價慘重!另外,羥氯喹本身具有降低自身免疫性風暴的有益功能。此外,氯喹還具有改善患者的酸鹼平衡水平的作用。

羥氯喹HCQ是繼青黴素之後的第二次醫學革命嗎?

在1928年蘇格蘭科學家亞歷山大·弗萊明(Alexander Fleming)發現青黴素之前,細菌是主要的死亡原因。自1942年起,醫學界開始使用青黴素來治療細菌感染,醫學界這種漫長的黑暗夜晚已經結束。其中包括抗葡萄球菌青黴素,氨基青黴素和抗假單胞菌青黴素。(5)它們來自青黴素真菌。青黴素的發現是治療人類疾病的醫學領域的一場偉大革命,其中許多疾病在青黴素之前非常致命。因此,為表彰亞歷山大·弗萊明(Alexander Fleming)博士,他與牛津大學的科學家霍華德·弗洛里(Howard Florey)博士和恩斯特·鮑裡斯·鏈博士(Ernst Boris Chain)共同獲得了諾貝爾生理學或醫學獎,後者開發了改良的青黴素配方,廣泛用於臨床治療。

在發現青黴素後的大約八十年中,整個醫學界在世世代代的共同努力下,在尋找有效的方法來發現,配製和提供任何化學藥品方面幾乎沒有取得什麼進展(如果有的話)對抗任何過濾性慢病毒的藥物或藥物,包括流感,埃博拉病毒,艾滋病,SARS-CoV和Covid-19。我們在一次偉大的慶典中親眼目睹了人類應該如何感恩上帝,這是祂在1928年以後的第二次恩典。在這一次瘟疫中尚未被擊敗的致命敵人正在通過整個過濾慢病毒的爆發,導致嚴重的致命病毒綜合徵。從流感,Covid-19到艾滋病。由於Covid-19的嚴重性以及急性感染,濾過性慢病毒引發的疾病迅速傳播的潛力以及缺乏公認的有效且安全的病毒體內抑制劑,因此確定抗大流行病很重要可有效用於治療和預防潛在慢病毒感染的藥物羥氯喹的廣泛療效意義重大。

結合此處提供的數據,顯示了與患者治療相適應的羥氯喹HCQ劑量對細胞培養物中的病毒抑制作用,建議立即,完全和永久FDA批准羥氯喹HCQ用於預防和治療這種過濾性慢病毒引發的流行病,如急性流感,Covid-19強烈推薦SARS流行患者。

參考資料:

1 Vincent,M.J。等人。 氯喹是SARS冠狀病毒感染和擴散的有效抑制劑。 Virol J 2,69,doi:10.1186 / 1743-422X-2-69(2005)。

2 Zhao,M.細胞因子風暴和COVID-19中的免疫調節療法:氯喹和抗IL-6單克隆抗體的作用。 Int J Antimicrob Agents 55,105982,doi:10.1016 / j.ijantimicag.2020.105982(2020)。

3 Derwand,R.,Scholz,M.和Zelenko,V. COVID-19門診患者:鋅加小劑量羥氯喹和阿奇黴素的早期風險分層治療:回顧性病例系列研究。 Int J Antimicrob Agents 56,106214,doi:10.1016 / j.ijantimicag.2020.106214(2020)。

4 Ng,M.L.,Tan,S.H。,參見E.E.,Ooi,E.E。和Ling,A.E.SARS冠狀病毒在vero細胞中的早期感染。 J Med Virol 71,323-331,doi:10.1002 / jmv.10499(2003)。

5 Tan,J.S。&File,T.M.,Jr.Antiseseudomonal青黴素。 Med Clin North Am 79,679-693,doi:10.1016 / s0025-7125(16)30032-3(1995)。

作者簡介:葉寧,美國執業律師,畢業於美國長春藤大學賓夕法尼亞大學法學院。葉寧的祖上歷代中醫草藥朗中,他從小接觸溫病學等中醫典藉。在長達數十年律師生涯中,特別是在幫助美國國家健康中心等世界前沿生命科學研究中心各科頂尖專家的業務中,接受到醫學科學的最新最前沿信息。

 

責任編輯:高義

This manuscript was written under the urgent pressure of being motivated in saving lives of Covid-19 epidemics which has claimed more than 500,000 American lives since February 2020, most likely due to virtual absence of correct therapy. The author is not a professional virologist/epidemiologist. With family background of Chinese traditional herbal medicine, this author had extensive learning experience interacting in appendices nature with the world’s improved ways to produce and concentrate on the drug and prove its antiviral effects following topnotch scientists in medical science mostly in the NIH, the world’s most prestigious headquarter compound representing the most cutting-edge life science development. Since January 2020, this author contributed 5 Covid-19 alternative therapy package involving hot-lemon ginger tea to ways to reverse protein deficiency and over-fatigue, to HCQs, in China, as partially accepted methodology guidelines whose mere motive is to save lives from devastating Covid pandemics.  The driving cause pushing this author to involve himself in humanitarian crusade in saving lives of Covid-19 patients during starting the darkest period is what he was shocked by what he watched video footage taken in Wuhan, China that many collapsed in the streets and deeply scared people having committed suicide by jumping off from the windows of the high rise apartment buildings. “You don’t have to die with this kind of disease as corona virus infected syndrome!” He out-cried.  He has the answer to get fully recovery, for the super majority of Covid patients.  Mr. Ye accurately forecast in earlier February, 2020 that the turning point with 95%+ death toll reduction throughout China should appear in March 2020, in comparison to Academician Zhong Nanshan’s forecasting that the turning point would be in May 2020. Mr. Ye’s forecasting that the turning point in the United States should be May 2020 was unfortunately failed because President Donald Trump’s courageous advocacy of HCQ was defeated by the establishment in April followed with FDA’s revocation of temporary “clinical trial” permit, and further followed with swift climbing up of death tolls of Covid-19 casualty from hospitals throughout the nation. Ning Ye’s legal battle for the sake of HCQ seeking for Writ of Mandamus with U.S. District Court for the Southern District of New York (20-3067-RA) did not result in prompt and positive outcome. Now, with all non-medical aspects in interfering the HCQ as the crusade to treating filtering lentivirus epidemics dying down after general election, it is high time to concentrate upon this noble cause in saving lives.

  1. The discovery of HCQ and its anti-virus effects

Chloroquine (CQ), a 9-aminoquinoline that was identified in 1934. Hydroxychloroquine (HCQ), the advanced type of CQ with more effective therapeutic, is an ancient drug in the random selection during the clinical trials starting in China, which has been used in fighting against lethal pandemic. Before, HCQ, there has been no effective drug for the treatment of various infectious diseases caused by lentivirus from Flu to Covid-19, even AIDS. It has been shown that HCQ has effective therapeutic, virus-suppression and lower by effect has strong antiviral effects on filtering lentivirus ranging from flu virus SARS-CoV and SARS-CoV2 and its variation ramification Covid-19 virus infection of primate cells. In addition, clinical trial proves that each member receiving 200-600mg HCQ daily dosage showed 100% recovery result during the three to five-day treatment for acute Flu patients.

  1. Clinical evaluation of HCQ in the treatment of Covid-19

Severe acute respiratory syndrome (SARS) and its neo-type variation, Covid-19, is caused by a newly discovered coronavirus SARS-CoV2. Covid-19 is an emerging disease that was first reported in Hubei Province, China, in late 2019. The disease rapidly spread to the entire world with most severe impact upon the United States having claimed six digits Covid-19 related deaths and worldwide efforts have failed for non-medical complications, very unfortunately to humanity, in the identification of the etiological agent coronavirus, a novel member of the family Coronaviridae, coupled with wasteful failure in finding and identification of most effective and available treating drug for complications irrelevant to medical science for its own sake. No effective prophylactic or post-exposure therapy had been available before 2005.1

Of note, it has been reported that HCQ administration with daily dosage of 400-800mg HCQ treating Covid-19 pre-complication patients received 100% sweeping and miracle results, all virus were eliminated.1 Dr. Vladimir Zelenko and others used his HCQ-based cocktails has successfully treated hundreds of Covid-19 patients in clinic trial and he recently predicted that neo-variation of Covid-19 virus spreading from the UK is also within the sphere of HCQ’s therapeutic zone.2

In addition, there are some reports of failure or inadequacy in the clinical trials of using HCQ to treat Covid-19 patients. Such sporadic failures were used to maliciously attack HCQ. The unrevealed reason is probably due to insufficient or excessive dosage, or too late. Cocktail therapy is not necessarily required in all Covid-19 cases, and large doses of antibiotics are not required for early stage Covid-19 patients without bacterial infection or inflammation. Using HCQ too late, however, for late-stage patients who have experienced non-viral complications triggered by the Covid-19 virus. In the late stages, the process requires supportive symptomatic treatments such as antibiotics, anti-inflammatory, antithrombotic/anticoagulation and/or anti-autoimmune storm. In addition, as the experience in Sweden shows, preventive measures must be taken.

  1. Low toxicity of HCQ

The improved formula HCQ has been widely used to treat human diseases such as malaria, amoebiosis, HIV, Lupus and autoimmune cytokine storms, without significant detrimental side effects which appears absolutely safe even to pregnant women. Though such safety by effects, which appears much, much safer than most, if not all, FDA approved chemical agents in chemotherapy treating cancer patients, have long been contained in the Drug Codes in the most civilized nations, however, a one-year long clinical trial to observe HCQ’s safety was conducted by NIH related clinic for a control group of 103 Lupus patients from March 2012 to March 2013. Daily dosage of HCQ 200-400 mg for each member of controlled group, the accumulated total quantity was up to 144000 mg.  None, repeat, none in the HCQ group suffered any visible side effects.3

An HCQ’s molecule “weight” is 434 (433.96). An effective elimination in in vitro shows 10μM CQ or 5 μM HCQ, eliminated broad spectrum filtering lentivirus by 100%.  After all possible degrading ratio is taken into account through mathematical models, the average dosage to heal a Covid-19 or Flu patient with HCQ should be 2.17 mg/kg body weight. For mid and later phase Covid-19 patients, 6.21 mg/kg body weight. Therefore, a daily dosage 200-600mg, oral is sufficient, and a weekly dosage will effectively repeal all viral infection with elimination of virus in vivo. Due to the fact that HCQ shows extreme low toxicity which does not show any statistical value for short period (e.g., less than 6 months period of continuous prescription) administration in clinical trials, if the clinical dosage be increased up to 400-800 mg daily oral dosage for the first two days to relatively overweight patients, it causes no toxicity response.

  1. Preinfection and postinfection effect of CQ and HCQ

HCQ demonstrates full-scale effective in preventing the spread of filtering lentiviral epidemics ranging from acute Flu to Covid-19 and SARS in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with HCQ prior to or after such filtering lentivirus infection on both in vitro experiment in laboratories and in vivo clinical trials in China.1

Recently, Vincent et al., reported that pretreatment with 0.1μM CQ or 0.05μM HCQ, reduced infectivity by 28%, and 10μM CQ or 5 μM HCQ, reduced infectivity by 100% in Vero E6 cells (Figure 1).1 The antiviral effects by CQ immediately after virus adsorption was also evaluated, they found that adding chloroquine 3 and 5 h after virus adsorption effectively removed infected virus (Figure 2).1 Electron microscopic analysis indicated the appearance of significant amounts of extracellular virus particles 5-6 h after infection.4 These data demonstrated that pretreatment of Vero E6 cells with CQ rendered these cells refractory to SARS-CoV infection, and that administration of CQ after infection also showed curative effect.

Figure 1. Prophylactic effect of chloroquine.

Figure 2. Timed post-infection treatment with chloroquine.

4.2 HCQ prevented the binding of Covid-19 with spike glycoprotein

When added extracellularly, the non-protonated portion of CQ enters the cell, where it becomes protonated and concentrated in acidic, low-pH organelles, such as endosomes, Golgi vesicles, and lysosomes. CQ can affect virus infection in many ways, and the antiviral effect depends in part on the extent to which the virus utilizes endosomes for entry. In addition to the well-known functions of HCQ’s such as elevations of endosomal pH balancing, the drug appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2 (ACE2). This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in sweeping and miracle inhibition of infection and spread of Flu syndrome, SARS CoV and Covid-19 at clinically admissible concentrations by all clinical trials in hospitals throughout China.

Over eighty years of antiviral drug research, scientists have long focused on blocking the attachment between the viral spike glycoprotein (similar to the signal output antenna) and the host cell’s ACE2 receptor, to eliminate viral attachment to the cellular receptor that initiates a viral infection. Taking example of Covid-19 and Sars, budding of the SARS-CoV occurs in the Golgi apparatus and results in the incorporation of the envelope spike glycoprotein into the virion. The spike glycoprotein is a type I membrane protein that facilitates viral attachment to the cellular receptor and initiation of infection, and angiotensin-converting enzyme-2 (ACE2) has been identified as a functional cellular receptor of such filtering lentivirus including SARS-CoV and Covid-19. Vincent et al., have recently shown that the processing of the spike protein was affected by furin-like convertases and that inhibition of this cleavage by a specific inhibitor abrogated cytopathicity and significantly reduced the virus titer (Figure 3).1 In contrast, the antiviral effect of HCQ is probably not due to alteration of virus glycoprotein biosynthesis and processing. Consistent with this previous analysis,1 they observed the presence of a larger protein, which is referred to here as oligomers. Recently, Song et al. provided evidence that these are homotrimers of the SARS-CoV spike protein and were incorporated into the virions.

Figure 3. Effect of lysomotropic agents on the cell-surface expression and biosynthesis of ACE2.

Future clinical application of HCQ in the treatment of Covid-19

Vaccines belongs to in vivo immune system enhancement, not a chemical agent virus killer that directly eliminates viruses, which was shown 100% elimination of virus in vitro when the density of HCQ reached 10MU. For such viruses with too fast intergenerational mutations, such as that of Covid-19, whether the vaccine development speed can match that intergenerational mutation, and the toxicity evaluation may not have been crystal clear. Hydroxychloroquine has proven effective or even full effect with none or insignificantly little toxic side effects in vivo. We have witnessed today that a landmark turning point led by the HCQ as a proven effective broad spectrum anti-virus agent with insignificant little by-effect of toxicity has brought the Good News of Great Grace from Lord, in saving millions of pandemic virus patients as a groundbreaking medical science revolution just like discovery of Penicillin to eliminate various lethal bacteria eighty some years before. In addition, chloroquine itself has the beneficial function of degrading autoimmune storms.  Moreover, chloroquine also has the effect of improving the pH balancing level of the patients.

Is HCQ the second revolution in medical science after penicillin?

Before Penicillin was discovered in 1928 by Scottish scientist Alexander Fleming, bacteria  was the primary cause of death. This long night of darkness in medical science treating human disease has been ended when Penicillin was used to by medicinal society to treat bacteria infections starting 1942. The epoch making new era started when there are several enhanced penicillin families which are effective against additional bacteria; these include the antistaphylococcal penicillinsaminopenicillins and the antipseudomonal penicillins.5 They are derived from Penicillin fungi. Discovery of Penicillin is a great revolution in medical science treating human diseases many of which had been deadly before Penicillin. Consequently, in recognition of Dr. Alexander Fleming, a Nobel Prize in Physiology or Medicine was awarded to him sharing with Dr. Howard Florey and Dr. Ernst Boris Chain, scientists with Oxford University who developed improved penicillins formulas.

During the same period of approximately eight decades after discovery of Penicillin, the entire medical community through out of the world with orchestrated efforts by generations, has made little progress, if any, to find effective way to discover, formulate and made it available any chemical agents or drugs in fighting against any filtering lentivirus, ranging from that of Flu, of Ebola, of AIDS, of SARS-CoV, and of Covid-19. We have witnessed in great celebration that humanity, thanks the God, has encountered her second year of 1928, this time, yet to be defeated lethal enemy is filtering lentivirus probably by its entire family, which causes such crippling or deadly virus triggering human diseases ranging from Flu, Covid-19 to AIDS. Due to the severity of Covid-19 as well as acute Flu infection, the potential for rapid spread of the filtering lentivirus triggered diseases, and the absence of proven effective and safe in vivo inhibitors of the virus, it is important to identify anti-pandemic drug that can effectively be used to both treat and prevent potential lentiviral infections.

Together with data presented here, showing virus inhibition in cell culture by HCQ doses compatible with patient treatment, recommendation of immediate, full and permanent FDA approval of HCQ to be used in prevention and treating such filtering lentivirus triggered epidemic as Acute Flu,Covid-19 and SARS epidemic patients is strongly recommended.

References

1              Vincent, M. J. et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2, 69, doi:10.1186/1743-422X-2-69 (2005).

2              Zhao, M. Cytokine storm and immunomodulatory therapy in COVID-19: Role of chloroquine and anti-IL-6 monoclonal antibodies. Int J Antimicrob Agents 55, 105982, doi:10.1016/j.ijantimicag.2020.105982 (2020).

3              Derwand, R., Scholz, M. & Zelenko, V. COVID-19 outpatients: early risk-stratified treatment with zinc plus low-dose hydroxychloroquine and azithromycin: a retrospective case series study. Int J Antimicrob Agents 56, 106214, doi:10.1016/j.ijantimicag.2020.106214 (2020).

4              Ng, M. L., Tan, S. H., See, E. E., Ooi, E. E. & Ling, A. E. Early events of SARS coronavirus infection in vero cells. J Med Virol 71, 323-331, doi:10.1002/jmv.10499 (2003).

5              Tan, J. S. & File, T. M., Jr. Antipseudomonal penicillins. Med Clin North Am 79, 679-693, doi:10.1016/s0025-7125(16)30032-3 (1995).

責任編輯:高義

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