비즈니스 모델
January 2015
Over the last few years it has become possible to obtain simvastatin 10 mg over-the-counter in the United Kingdom and a potential increase in self-medication is predicted in other countries as well.
Can I buy statins over the counter?
Low-dose statins are available at some pharmacies without a prescription, but they are not a substitute for prescription statins or for making lifestyle changes to reduce your cholesterol level. If you are at high risk of heart disease, your doctor may prescribe a statin for you.
저용량을 처방 없이 사게 하고 그 다음에 제약사와 장기 계약을 해서 스타틴을 판매한다.
[전석진] [오후 9:49] 기영아 자니?
[전기영 최신] [오후 9:50] 아직 왜?
[전석진] [오후 9:50] 응 스타틴 연구하다 보니 비지니스 모델 아이디어가 생겨서 검증해 보려고...
[전기영 최신] [오후 9:50] 말씀해 보시죠
[전석진] [오후 9:51] 영국에서는 저용량 슽타틴을 over the counter 약으로 (계산대 약이라고 하나? ) 판매하고 있고 다른 나라도 이와 같은 움직임이 있다고 하더라고....
[전석진] [오후 9:52] 그렇다면 우리나라에서도 스타틴을 계산대약으로 하면 우리가 제약사에서 스타틴을 장기 구매 계약을 하고 사서 계산대에서 판매하면 돈이 되지 않을까 해서...
[전석진] [오후 9:53] January 2015
Over the last few years it has become possible to obtain simvastatin 10 mg over-the-counter in the United Kingdom and a potential increase in self-medication is predicted in other countries as well.
https://www.sciencedirect.com/science/article/pii/S1590865814005970
[전기영 최신] [오후 9:53] 근데 아직 코로나에 효과있다고 임상결과가 나온건 아니어서
그리고 스타틴의경우 근육통이나 근육이 부실해지는 부작용은 보고되고 있어요
[전기영 최신] [오후 9:54] 저용량의 경우는 이 부작용을 최대한 억제하는 수준인것 같으네
[전석진] [오후 9:55] 근육통 부작용은 아직 연구 안했고 당뇨와 간 독성 문제는 별 문제 없는 것으로 결론이 났음. 근육통 문제는 고용량 스타틴의 경우 발생하는데 스타틴을 비타민 처럼 먹는 것은 1주일에 한번 정도 저용량으로 먹는 것이 좋다는 연구가 있음.
[전기영 최신] [오후 9:56] 니가 보내준 자료를 보면 스타틴이 코로나 바이러스를 약화시키고 염증을 억제한다는 개연성은 이해가 되는데
[전석진] [오후 9:56] 응 그외에 한 20가지 좋은 효과가 있어. 노화 방지 효과를 포함하여...
[전석진] [오후 9:57] 심지어는 간질환 치료제로도 쓰이고 있데...
[전석진] [오후 9:57] 간질환 약은 신통한 것이 없고 간 질환은 침묵으 장기가 한번 발견되면 끝인 경우가 많은데 이것도 예방할 수 있고...등등...
[전기영 최신] [오후 9:58] 아스피린이 심장병예방을 도와준다는 보도가 나왔을때 아동용 아스피린이 한때 무지 팔린적이 있어요. 그리고 그 이론은 아직도 유효하고 근데 무슨 이유에서인지 더이상 발전이 안되네... 물론 내가 모를수있는 확률이 더 높지만
[전석진] [오후 9:59] 아스피린은 심혈관계에 좋은데 22%가 치료되고 부작용은 위 출혈인데 22%의 위 출혈이 있데 그래서 갑자기 시장에서 사라지게 된 것임.
[전기영 최신] [오후 9:59] https://youtu.be/MK439-xiNTU
[전기영 최신] [오후 10:01] https://youtu.be/aIgE--yB4kU
[전기영 최신] [오후 10:01] 이 외에도 많이 있어 심심하거나시간날때 한번 보세요
[전석진] [오후 10:02] 응 다 나와 있는 말들이고 이에 대한 전문적인 연구가 많아. 약사가 아니라 의학 교수들에 의한 연구....
[전기영 최신] [오후 10:02] 그래서 소 용량의 어린이 아스피린을 사먹었지 위에 부담이 가지 않도록
[전기영 최신] [오후 10:03] 아는 내용이면 다행이고
[전석진] [오후 10:03] 응 그래도 아스피린은 기적의 약은 아니야...스터탄은 당뇨환자들도 먹고 간질환자도 먹어.
[전석진] [오후 10:04] 근육통은 아직 연구를 안해봤는데 지금 간독성 문제 연구하고 있으니 아마 내일 모래 쯤이면 연구 시작 가능할 것 같고...
[전기영 최신] [오후 10:04] 너말고, 국제 변호사 말고, 의사 선생님을 설득할수 없을까?
[전석진] [오후 10:05] 응 약학 대학원 수석 졸업한 연구소에 있는 약사가 나의 논문을 검토중에 있어...
[전석진] [오후 10:05] 그런데 비지니스 모델은 그 친구와 이야기할 필요는 없잖아.
[전기영 최신] [오후 10:07] 분야가 분야인지라... 검토 결과 나오면 보자 나도 아는 의사분들 약사분들에게 물어볼께
일반약, 처방없이 살수있는. 으로 규정이 가능한지도 알아보아야지
[전석진] [오후 10:07] 다른 친구 하나는 제약사를 접촉하여 아예 약을 제조하는 것을 생각해 보자고 하는데 이것은 돈이 많이 들것 같고....
[전석진] [오후 10:08] 그 규정은 있어.
[전기영 최신] [오후 10:08] 스타틴 특허가없으면 복제약 제조는 어렵지 않아
[전석진] [오후 10:08] 그렇지...
[전기영 최신] [오후 10:10] 특정 성분함량 얼마이하면 처방없어도 된다 뭐그런 규정이겠지
그래도 식약처 인증은 받아야되고 그절차나 소요시간이 얼마걸리는지 알아볼께
[전석진] [오후 10:11] 제4조(심사기준) ① 의약품의 분류에 관한 심사는 다음 각호의 기준에 의한다.
1. 전문의약품은 제2조제1항의 규정에 해당되는 의약품이어야 한다.
2. 일반의약품은 제2조제2항의 규정에 해당되는 의약품으로 다음 각목에 적합하여야 한다.
가. 주로 가벼운 의료분야에 사용되며, 부작용의 범위가 비교적 좁고 그 유효성·안전성이 확보된 것
나. 일반국민이 자가요법(Self-medication)으로 직접 사용할 수 있는 것으로 적응증의 선택, 용량 및 용량의 준수, 부작용의 예방이나 처치 등에 대하여 일반국민이 스스로 적절하게 판단할 수 있는 것
다. 원료의약품의 성분 및 그 분량은 유효성 또는 안전성을 충분히 확인할 수 있는 것이어야 한다. 다만, 원칙적으로 작용이 완화된 것이어야 하고 작용이 격렬하거나 습관성·의존성이 있는 것은 제외한다.
라. 적응증은 대체로 경미한 질병의 치료·예방 또는 건강의 유지증진 등의 범위를 넘어서는 안되며, 원칙적으로 의사의 진단, 치료에 따르는 것...
[전석진] [오후 10:11] 지정 신청을 할 수 있어.
[전기영 최신] [오후 10:11] 하여간 연구해봅시다
문제는 스타틴의 코로나에 대한 효능이겠지. 그에 대한 증명하고
[전석진] [오후 10:12] 그건 2020 노벨 생리학상 의학상 수상자인 찰스 라이스가 해주겠지.
[전기영 최신] [오후 10:13] 보내준 규정을 잘읽어보아야 되겠으나 일견해보니 이거 이현령비현령으로 보인다
잘읽어볼께
[전석진] [오후 10:14]
코로나바이러스 예방과 치료의 획기적인 연구 결과- 콜레스테롤 강하제의 사용
변호사 전석진
미국에서는 벌써 이천만명에 가까운 사람들이 코로나 백신을 맞았는데 우리나라는 많이 뒤처져 있다.
그런데 미국에서 이번 달 8. 에 발표된 연구에 의하면 이러한 상황을 역전시키는 방법이 있다.
그것은 백신을 접종할 수 있게 되기 전에 이미 그 부작용에 대하여 검토가 끝난 콜레스테롤 강하제를 광범위하게 사용하자는 것이다.
놀랍게도 이 연구는 암 치료 연구자인 Francisco J. Sánchez-Rivera 박사와 찰스 M. 라이스 2020년 노벨 생리학, 의학상 수상자를 팀으로 하는 연구팀에서 발견된 성과이다. 연구 발표일은 2021.1.8.이다.
연구팀들은 암 연구에 사용되는 크리스퍼 캐스나인이라는 기술을 사용하였다.
연구자들은 호스트 셀의 유전자들을 시스템적으로 제거해 가면서 유전자의 어떤 기능이 ...
[전석진] [오후 10:14] 그래 나는 근육 통증 연구해 볼게...
[전기영 최신] [오후 10:14] ㅇㅋ talk you later
[전석진] [오후 10:15] ㅇㅋ 굿나잇! 탱큐!
스타틴 연구의 시발점은 2021.1.8.이다
The results of their collaboration are now in. Published on December 9 and 14, 2020, in two articles in the journals Cell and Cell Host and Microbe, the studies provide a comprehensive roadmap of the host factors — the infected person’s genes, proteins, and other molecules — that SARS-CoV-2 uses to invade and replicate inside human cells.
Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks
William M. Schneider 5
Joseph M. Luna 5
H.-Heinrich Hoffmann 5
Margaret R. MacDonald
Charles M. Rice
John T. Poirier 7
Show all authors
Show footnotes
Published:December 09, 2020DOI:https://doi.org/10.1016/j.cell.2020.12.006
Cell/Impact factor
38.637
Nature/Impact factor
42.778
Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors
H.-Heinrich Hoffmann 8
Francisco J. Sánchez-Rivera 8
William M. Schneider 8
Margaret R. MacDonald
John T. Poirier 8
Charles M. Rice 9
Show all authors
Show footnotes
Published:December 14, 2020DOI:https://doi.org/10.1016/j.chom.2020.12.009
Both studies relied on the genome-editing tool CRISPR/Cas9. This versatile tool allows scientists to make precise cuts in the genome. The MSK, Rockefeller, and NYU scientists used CRISPR to systematically knock out genes in human cells and ask whether the loss of that gene’s function impaired the virus’s ability to infect, reproduce in, and ultimately kill the cells.
The combined efforts revealed some surprising host factors and potential drug candidates. One set of factors was involved in maintaining cholesterol balance in cells. Conceivably, Dr. Sánchez-Rivera says, existing drugs that modify cholesterol levels could be repurposed to fight COVID-19 infection.
Another factor — much less familiar to the scientists — was a protein called TMEM41B. “Only a handful of papers in total have ever been written about this protein,” Dr. Sánchez-Rivera says. “But we found that it is absolutely essential for SARS-CoV-2 replication. If you remove TMEM41B from host cells, viral replication is completely halted.”
“We hypothesized that the host factors that are shared among this family of viruses may be required for future pandemic coronavirus strains as well,” Dr. Sánchez-Rivera explains. “That would allow us to be more prepared for potential future outbreaks.”
Statins interact with several different signaling pathways to exert their anti-inflammatory and vasculoprotective effects. They also variably affect cholesterol content of cell membranes and interfere with certain coronavirus enzymes involved in receptor-binding. Both these actions may influence SARS-CoV-2 entry into human cells.
Sánchez-Rivera says, existing drugs that modify cholesterol levels could be repurposed to fight COVID-19 infection.
Given that statins – one of the most widely used class of drugs in the world – block mevalonate
production via inhibition of the HMGCoA reductase and have been recently associated with improved
outcomes among COVID-19 patients (Fajgenbaum and Rader, 2020; Zhang et al., 2020), it is tempting
to speculate that pharmacological modulation of the mevalonate pathway could be a promising strategy
for treating COVID-19.
The Cox model applied to the CSH function (HR = 0.58(CI: 0.39-0.89); p = 0.01) and the competing risks FG model (HR = 0.60(CI: 0.39-0.92); p = 0.02) suggest that statins are associated with reduced COVID-19-related mortality.
Conclusions: A lower SARS-CoV-2 infection-related mortality was observed in patients treated with statin therapy prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.
The potential of cholesterol-lowering drug statin use to counteract SARS-CoV-2 mortality and the mechanisms triggered by these compounds in infections, has been suggested by our group [2, 3]. A recent retrospective study by Zhang et al. [4] performed in a very large cohort of 13,981 patients hospitalized for COVID-19 in Hubei Province, China, highlighted a reduced mortality risk in statin user patients applying impressive multiple statistical models, used to adjust for potential bias, and sensitivity analyses to limit the overall unmeasured confounders.
The Cox model applied to the CSH function [HR = 0.58(CI: 0.39–0.89); P = 0.01] and the competing-risks FG model [HR = 0.60 (CI: 0.39–0.92); P = 0.02] suggest that statins are associated with reduced COVID-19-related mortality.
Conclusions
A lower SARS-CoV-2 infection-related mortality was observed in patients treated with ST prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.
22.673
Journal Impact IF History
Published: 15 October 2020
Logistic treatment models showed a lower chance of ICU admission for statin users when compared to non-statin users (ATET: Coeff (risk difference): − 0.12 (− 0.23, − 0.01); p = 0.028). There were no other significant differences in other outcomes. Statin use was independently associated with lower ICU admission. This supports current practice to continue prescription of statins in COVID-19 patients.
In-Hospital Use of Statins Is Associated with a
Reduced Risk of Mortality among Individuals with
COVID-19
Graphical Abstract
Highlights
d Statin treatment among 13,981 patients with COVID-19 was
retrospectively studied
d Statin use in this cohort was associated with a lower risk of
all-cause mortality
d Adding an ACE inhibitor or an ARB did not affect statinassociated outcome in the cohort
d The benefit of statins among this cohort may be due to
immunomodulatory benefits
Authors
Xiao-Jing Zhang, Juan-Juan Qin,
Xu Cheng, ..., Jingjing Cai, Jiao Guo,
Hongliang Li
Correspondence
jiahong.xia@hust.edu.cn (J.X.),
yibinwang@mednet.ucla.edu (Y.W.),
caijingjing83@hotmail.com (J.C.),
guoj@gdpu.edu.cn (J.G.),
lihl@whu.edu.cn (H.L.)
In Brief
Statins have anti-inflammatory benefits
and were suggested as an adjunct
therapy for COVID-19. But statins may
increase the expression of ACE2, the
receptor for SARS-CoV-2. Here, Zhang
et al. retrospectively analyzed 13,981
COVID-19 cases and found that inhospital statin use is associated with a
lower risk of all-cause mortality.
August 4, 2020
that fluvastatin may have a
moderate beneficial effect on SARS-CoV-2 infection
by modulating protein translation.
These showed that the use of statins prior to hospitalization for this condition did not confer a benefit in terms of reduced mortality. However, when administered to COVID-19 patients following hospitalization, the risk of mortality fell by 47%, with the odds of death dropping by 43%, compared to non-users.
This stringent meta-analysis reports on a total of over 110,000 patients, making it the most high-powered study now available. The use of separate assessments for COVID-19 mortality and ICU admissions following statin administration also led to distinct risk evaluations for these outcomes.
Overall, the lower risk of mortality with statin use post-admission is likely to be underestimated since many of these patients were put on statins for other cardiovascular indications, which put them at higher risk of death. The findings, therefore, support continuing statin use in patients who are already taking these drugs.
The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared to the GM non-statin group (17.4%; p = 0.045). The Cox model applied to the CSH function (HR = 0.58(CI: 0.39-0.89); p = 0.01) and the competing risks FG model (HR = 0.60(CI: 0.39-0.92); p = 0.02) suggest that statins are associated with reduced COVID-19-related mortality. Conclusions: A lower SARS-CoV-2 infection-related mortality was observed in patients treated with statin therapy prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19. Keywords: COVID-19; Cardiovascular risk; Mortality; SARS-CoV-2; Statins
SOURCE DATA
TRANSPARENT PROCESS
Cholesterol 25‐Hydroxylase inhibits SARS‐CoV‐2 and other coronaviruses by depleting membrane cholesterol
Here, we report that one of the interferon‐stimulated genes (ISGs), cholesterol 25‐hydroxylase (CH25H), is induced by SARS‐CoV‐2 infection in vitro and in COVID‐19‐infected patients. CH25H converts cholesterol to 25‐hydrocholesterol (25HC) and 25HC shows broad anti‐coronavirus activity by blocking membrane fusion. Furthermore, 25HC inhibits USA‐WA1/2020 SARS‐CoV‐2 infection in lung epithelial cells and viral entry in human lung organoids. Mechanistically, 25HC inhibits viral membrane fusion by activating the ER‐localized acyl‐CoA:cholesterol acyltransferase (ACAT) which leads to the depletion of accessible cholesterol from the plasma membrane. Altogether, our results shed light on a potentially broad antiviral mechanism by 25HC through depleting accessible cholesterol on the plasma membrane to suppress virus–cell fusion. Since 25HC is a natural product with no known toxicity at effective concentrations, it provides a potential therapeutic candidate for COVID‐19 and emerging viral diseases in the future.
Hypothesis:
Considering that simvastatin, and probably statins in general, interfere with SARS-cov2 cellular uptake and some inflammatory pathways activated by the virus, those patients
on statin therapy should be less vulnerable to infection and their clinical course and
prognosis should be better than that in individuals not on statin therapy.
Statins Reduce COVID-19 Severity, Likely by Removing Cholesterol That Virus Uses to Infect
Analyzing anonymized patient medical records, UC San Diego researchers discovered that cholesterol-lowering statins reduced risk of severe COVID-19 infection, while lab experiments uncovered a cellular mechanism that helps explain why
September 23, 2020 | Heather Buschman, PhD and Jeanna Vazquez
Statins are well known for their anti-inflammatory effects5 and some hospitals included them in the
COVID-19 treatment protocol.6
Here, we summarize main points that should be considered before
incorporating this class of drugs in COVID-19 treatment regimen.
ORIGINAL ARTICLE| VOLUME 15, ISSUE 1, P68-78, JANUARY 01, 2021
PDF [197 KB]
Published:December 21, 2020
Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospitals during COVID-19 pandemic in Italy
Gianfranco Mitacchione
Marco Schiavone
Antonio Curnis
Published:December 21, 2020
Infection with SARS-CoV-2 causes downregulation of ACE2. This
increases vulnerability to the damaging effects of AT II, which is
thought to be responsible for the lung injury that is seen in many
COVID-19 patients. The dual roles played by ACE2 as a protector
against the harmful effects of the hyperinflammatory response,
and as the receptor for SARS-CoV, has caused controversy
regarding the use of medications such as ACE-inhibitors (ACE-I)
and angiotensin-receptor blockers (ARBs). T
COVID-19 patients who are already on statin therapy
should also continue treatment if not contraindicated (ESC
guidance, 2020).
Statin use prior to admission was associated with reduced risk of severe COVID-19 (adjusted OR 0.29, 95%CI 0.11 to 0.71, p < 0.01) and faster time to recovery among those without severe disease (adjusted HR for recovery 2.69, 95%CI 1.36 to 5.33, p < 0.01). The association between statin use and severe disease was smaller in the COVID-negative cohort (p for interaction = 0.07). There was potential evidence of faster time to recovery with ARB use (adjusted HR 1.92, 95%CI 0.81 to 4.56). In conclusion, statin use during the 30 days prior to admission for COVID-19 was associated with a lower risk of developing severe COVID-19, and a faster time to recovery among patients without severe disease.
Further, statins may block SARS-CoV-2 infectivity via direct binding to the main protease.11 The purpose of this single-center observational study of patients hospitalized for COVID-19 was to investigate the association of use of statins, ACE inhibitors, or ARBs, with (1) progression to severe disease (death or intensive care unit [ICU] admission), and (2) time to the onset of severe disease or to recovery, defined as hospital discharge without development of severe disease.
Statin use was associated with an increased rate of recovery from COVID-19 among subjects who had not yet experienced severe disease (cause-specific adjusted HR [aHR] for recovery 2.69, 95%CI 1.36 to 5.33, p = 0.004). In adjusted models, neither ARB use (aHR 1.92, 95%CI 0.81 to 4.56, p = 0.14), nor ACE inhibitor use (aHR 1.32, 95%CI 0.69 to 2.50, p = 0.39) was significantly associated with increased rate of recovery. There was some evidence that statin use was also associated with reduced rate of development of severe disease (aHR 0.55, 95%CI 0.28 to 1.08, p = 0.08). Use of ACE inhibitors (aHR 1.14, 95%CI 0.65 to 1.98, p = 0.65) or ARBs (aHR 1.57, 95%CI 0.78 to 3.17, p = 0.21) was not significantly associated with rate of development of severe disease in these adjusted models.
In this series of 170 patients hospitalized for treatment of COVID-19 at UCSDH, use of statins prior to admission was associated with a more than 50% reduction in risk of developing severe COVID-19, after controlling for associated comorbid conditions and for concomitant use of ACE inhibitors or ARBs.
In a competing risks time-to-event analysis, there was strong evidence that statin use was associated with considerably faster time to recovery; there was weaker evidence for association with a reduced rate of progression to severe COVID-19.
There is some biologic plausibility for a protective role of statins in COVID-19 through known anti-inflammatory and immunomodulator effects as well as via upregulation of ACE2 and direct effects on the virus.
Statins may inhibit SARS-CoV-2 infectivity by direct binding and inhibition of the main protease, a key coronavirus enzyme.
Although SARS-CoV viruses employ ACE2 for cell entry, they have been shown in vivo to reduce ACE2 expression upon binding of the viral spike protein to the ACE2 receptor.17
ACE2 downregulation leads to excessive production of angiotensin, which has been causally linked to severe respiratory failure.17 Therefore, upregulation of ACE2 is another potential mechanism whereby statins (as well as ACE inhibitors and ARBs) might protect against COVID-19 lung injury.8 In observational studies, statins were associated with reduced influenza-related hospitalizations,10,18, 19, 20 and with improved outcomes in community acquired pneumonia and sepsis.21
In time-to-event analysis, when considered alone ARB medication use prior to admission was not a predictor of severe disease, but similar to statins, was associated with faster time to recovery. In multivariable analyses when both ARB and statin use were entered jointly in the model of time to recovery, the effect of ARB use was attenuated, while statin use retained a robust effect.
Our findings that obesity and diabetes are risk factors for severe outcomes in COVID-19 are consistent with prior reports.1,28,29
In summary, among patients hospitalized for COVID-19, use of statin medication prior to admission was associated with a reduced risk of severe disease and a faster time to recovery, after adjusting for demographics and comorbid conditions in this single-center observational study. Randomized clinical trials are underway to assess whether statin medications may improve outcomes among COVID-19 patients.
Science/Impact factor
41.845
Volume 136, 1 December 2020, Pages 149-155
The American Journal of Cardiology
Relation of Statin Use Prior to Admission to Severity and Recovery Among COVID-19 Inpatients
스타틴을 30일 전에 복용하면 회복 기간이 빠르다. 병원 자원을 아낄 수 있다.
ORIGINAL RESEARCH ARTICLE
Front. Med., 17 November 2020 | https://doi.org/10.3389/fmed.2020.584870
Association of Statin Use With the In-Hospital Outcomes of 2019-Coronavirus Disease Patients: A Retrospective Study
Result: A total of 2,147 patients with COVID-19 were enrolled in this study. Of which, 250 patients were on statin therapy. The mortality was 2.4% (6/250) for patients taking statins while 3.7% (70/1,897) for those not taking statins. In the multivariate Cox model, after adjusting for age, gender, admitted hospital, comorbidities, in-hospital medications and blood lipids, the risk was lower for mortality (adjusted HR, 0.428; 95% CI, 0.169–0.907; P = 0.029), acute respiratory distress syndrome (ARDS) (adjusted HR, 0.371; 95% CI, 0.180–0.772; P = 0.008) or intensive care unit (ICU) care (adjusted HR, 0.319; 95% CI, 0.270–0.945; P = 0.032) in the statin group vs. the non-statin group. After propensity score-matched analysis based on 18 potential confounders, a 1:1 matched cohort (206:206) was created. In the matched cohort, the Kaplan-Meier survival curves showed that the use of statins was associated with better survival (P = 0.025). In a Cox regression model, the use of statins was associated with lower risk of mortality (unadjusted HR, 0.254; 95% CI, 0.070–0.926; P = 0.038), development of ARDS (unadjusted HR, 0.240; 95% CI, 0.087–0.657; P = 0.006), and admission of ICU (unadjusted HR, 0.349; 95% CI, 0.150–0.813; P = 0.015). The results remained consistent when being adjusted for age, gender, total cholesterol, triglyceride, low density lipoprotein cholesterol, procalcitonin, and brain natriuretic peptide. The favorable outcomes in statin users remained statistically significant in the first sensitivity analysis with comorbid diabetes being excluded in matching and in the second sensitivity analysis with chronic obstructive pulmonary disease being added in matching.
Conclusion: In this retrospective analysis, the use of statins in COVID-19 patients was associated with better clinical outcomes and is recommended to be continued in patients with COVID-19.
Commentary: Statins, COVID-19, and coronary artery disease: killing two birds with one stone
Shiva Ganjali 1
Vanessa Bianconi 1
Peter E. Penson
Maciej Banach
Gerald F. Watts
Amirhossein Sahebkar
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Published:September 22, 2020
3/2020 vol. 16StatsCC BY-NC-SA 4.0Get citation
COVID-19/SARS-COV-2 / RESEARCH PAPER
Statins and the COVID-19 main protease: in silico evidence on direct interaction
Željko Reiner 1, Mahdi Hatamipour 2, 3, Maciej Banach 4, 5, Matteo Pirro 6, Khalid Al-Rasadi 7, Tannaz Jamialahmadi 8, 9, Dina Radenkovic 10, Fabrizio Montecucco 11, 12, Amirhossein Sahebkar 13, 8, 14
Introduction:
No proven drug and no immunisation are yet available for COVID-19 disease. The SARS-CoV-2 main protease (Mpro), a key coronavirus enzyme, which is a potential drug target, has been successfully crystallised. There is evidence suggesting that statins exert anti-viral activity and may block the infectivity of enveloped viruses. The aim of this study was to assess whether statins are potential COVID-19 Mpro inhibitors, using a molecular docking study.
Material and methods:
Molecular docking was performed using AutoDock/Vina, a computational docking program. SARS-CoV-2 Mpro was docked with all statins, while antiviral and antiretroviral drugs – favipiravir, nelfinavir, and lopinavir – were used as standards for comparison.
Results:
The binding energies obtained from the docking of 6LU7 with native ligand favipiravir, nelfinavir, lopinavir, simvastatin, rosuvastatin, pravastatin, pitavastatin, lovastatin, fluvastatin, and atorvastatin were –6.8, –5.8, –7.9, –7.9, –7.0, –7.7, –6.6, –8.2, –7.4, –7.7, and –6.8 kcal/mol, respectively. The number of hydrogen bonds between statins and amino acid residues of Mpro were 7, 4, and 3 for rosuvastatin, pravastatin, and atorvastatin, respectively, while other statins had two hydrogen bonds.
Conclusions:
These results indicate, based upon the binding energy of pitavastatin, rosuvastatin, lovastatin, and fluvastatin, that statins could be efficient SARS-CoV-2 Mpro inhibitors. This is supported by the fact that the effects of some statins, especially pitavastatin, have a binding energy that is even greater than that of protease or polymerase inhibitors. However, further research is necessary to investigate their potential use as drugs for COVID-19.
Furthermore, statin treatment can interfere with viral infectivity through inhibition of glycoprotein processing. Disruption of protease activity and decreased ratios of the mature glycoproteins to precursor form are possible mechanisms of the antiviral effect of statins. Disruption of the viral protease activity is an important therapeutic goal [16].
The main protease (Mpro) of a virus, in this case CoV, plays an important role in proteolytic maturation [17]. Consequently, it has been examined as a potential protein target to prevent infection expansion by inhibiting the cleavage of the viral polyprotein [18]. This might explain why statins could be useful in the treatment of COVID-19. The aim of this study was to assess whether statins might be potential COVID-19 Mpro inhibitors. Namely, most recently the SARS-CoV-2 main protease (Mpro), a key coronavirus enzyme, which is a potential drug target, has been successfully crystallised [19, 20]. Therefore, the idea was to investigate whether statins could be useful in the treatment of COVID-19 by directly affecting the virus particle.
We studied the affinity of seven statins (simvastatin, rosuvastatin, pravastatin, pitavastatin, lovastatin, fluvastatin, and atorvastatin), standard ligand, and protease inhibitors with the COVID-19 Mpro. Table I summarises the affinity (Kcal/mol), hydrogen bonds, and binding residues of these seven statins, standard ligand, and protease inhibitors with the COVID-19 Mpro, involved in COVID-19 infection. Statins had strong drug-like properties when docked along with known inhibitors against the Mpro. The ligands were sorted on the basis of binding strength and were compared with known inhibitors.
The docking results based on the binding energy of pitavastatin, rosuvastatin, lovastatin, and fluvastatin suggest that these statins might be potential COVID-19 Mpro inhibitors. Docking visualisation of the binding of different statins, standard ligand, and protease inhibitors with 6LU7 is shown in Figure 1.
However, we investigated whether statins could directly interact with the main protease enzyme of SARS-CoV-2. We found that there is a strong effect of some statins, especially pitavastatin, with a binding energy (the more negative delta G means stronger interaction), which is even greater than that of protease inhibitors. Docking studies may be of crucial value because until now no studies have investigated the effects of the chemical structure and inhibition of docking activity of statins on the main protease enzyme of SARS-CoV-2.
Because pitavastatin has already been shown to have a potent antiviral effect against Ebola virus [26], according to our results it could have a direct antiviral effect on SARS-CoV-2 as well. Based upon our results, rosuvastatin, lovastatin, and fluvastatin might also be useful in COVID-19 treatment.
The limitation of this study is in its in silico nature. Therefore, our results need to be confirmed by experimental studies, which might support our findings, as well as studies on patients with COVID-19, for whom until today no specific treatment exists.
In conclusion, besides their indirect effects on COVID-19, such as decreasing complications due to existing ASCVD mostly because of their anti-inflammatory and immunomodulatory effects, our results suggest that statins can directly affect the virus particle. Therefore, their efficacy concerning COVID-19, especially for pitavastatin, warrants further investigation.
Statin Use Associated with Lower COVID-19 Mortality, Spanish Study Shows
November 5, 2020
Patrick Campbell
Using data from more than 2000 patients presenting to more than a dozen medical centers across Spain, investigators concluded use of statins was associated with a 22-25% lower risk of mortality among patients hospitalized with COVID-19.
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Open AccessEditorial
Cholesterol in Relation to COVID-19: Should We Care about It?
by Dina Radenkovic 1,2OrcID,Shreya Chawla 2,Matteo Pirro 3,Amirhossein Sahebkar 4,5,6OrcID andMaciej Banach 7,8,9,*OrcID
1
Guy’s and St Thomas’ Hospital, London SE1 7EH, UK
2
Faculty of Life Sciences and Medicine, King’s College London, London SE5 9NU, UK
3
Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, 06123 Perugia, Italy
4
Halal Research Center of IRI, FDA, Tehran 314715311, Iran
5
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
6
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
7
Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz (MUL), Zeromskiego 113, 90-549 Lodz, Poland
8
Polish Mother’s Memorial Hospital Research Institute (PMMHRI), 93-338 Lodz, Poland
9
Cardiovascular Research Centre, University of Zielona Gora, 65-417 Zielona Gora, Poland
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(6), 1909; https://doi.org/10.3390/jcm9061909
Received: 8 June 2020 / Accepted: 16 June 2020 / Published: 18 June 2020
(This article belongs to the Section Cardiology)
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Abstract
Current data suggest that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease-19 (COVID-19) seems to follow a more severe clinical course in patients with cardiovascular disease (CVD), hypertension, and overweight/obesity. It appears that lipid-lowering pharmacological interventions, in particular statins, might reduce the risk of cardiovascular complications caused by COVID-19 and might potentially have an additional antiviral activity. It has been shown that high cholesterol levels are associated with more lipid rafts, subdomains of the plasma membrane that can harbour angiotensin-converting enzyme 2 (ACE2) receptors for the S-protein of SARS-CoV-2. Evidence of the importance of cholesterol for viral entry into host cells could suggest a role for cholesterol-lowering therapies in reducing viral infectivity. In addition to their lipid-lowering and plaque-stabilisation effects, statins possess pleiotropic effects including anti-inflammatory, immunomodulatory, and antithrombotic activities. Lower rates of mortality and intubation have been reported in studies investigating statin therapy in influenza infection, and statin therapy was shown to increase viral clearance from the blood during chronic hepatitis C infection. Statins may also serve as potential SARS-CoV-2 main protease inhibitors, thereby contributing to the control of viral infection. In this review, we elaborate on the role of cholesterol level in the process of the coronavirus infection and provide a critical appraisal on the potential of statins in reducing the severity, duration, and complications of COVID-19.
Keywords: atherosclerosis; cholesterol; coronavirus; COVID-19; lipid-lowering therapy; SARS-CoV-2; statins
News Releases
Statin Usage is Linked to a Lower Death Rate in Hospitalized COVID-19 Patients
07/02/2020
FINDINGS
A new study led by Chinese researchers in collaboration with UCLA's Dr. Yibin Wang, PhD, has shown that people hospitalized with COVID-19 who took statin drugs were less likely to die and less likely to need mechanical ventilation than those who did not take the cholesterol-lowering drugs. Hospitalized patients taking statins had a 5.2% mortality rate, compared to a 9.4% mortality rate in patients not taking statins from two groups of COVID-19 patients with matching clinic characteristics except statin usage.
SARS-CoV-2 Requires Cholesterol for Viral Entry and Pathological Syncytia Formation
David W. Sanders, Chanelle C. Jumper, Paul J. Ackerman, Dan Bracha, Anita Donlic, Hahn Kim, Devin Kenney, Ivan Castello-Serrano, Saori Suzuki, Tomokazu Tamura, Alexander H. Tavares, Mohsan Saeed, Alex S. Holehouse, Alexander Ploss, Ilya Levental, Florian Douam, Robert F. Padera, Bruce D. Levy, Clifford P. Brangwynne
Together with cell biological and biophysical approaches, the screen reveals an essential role for membrane cholesterol in spike-mediated fusion, which extends to replication-competent SARS-CoV-2 isolates. Our findings provide a molecular basis for positive outcomes reported in COVID-19 patients taking statins, and suggest new strategies for therapeutics targeting the membrane of SARS-CoV-2 and other fusogenic viruses.
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