Statins and the COVID-19 main protease: in silico evidence on direct interaction

Reiner, Željko; Hatamipour, Mahdi; Banach, Maciej; Pirro, Matteo; Al-Rasadi, Khalid; Jamialahmadi, Tannaz; Radenković, Dina; Montecucco, Fabrizio; Sahebkar, Amirhossein

doi:10.5114/aoms.2020.94655

Cited by 248 publications

(235 citation statements)

References 24 publications

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“…propylthiouracil, simvastatin, etc.) ( Shrivastava-Ranjan et al, 2018 ; Reiner et al, 2020 ; Santos-Beneit et al, 2020 ). These mentioned drugs can be utilized for further in vitro and in vivo experiments to better examine their efficacy.…”

Section: Discussionmentioning

confidence: 99%

A connectivity map-based drug repurposing study and integrative analysis of transcriptomic profiling of SARS-CoV-2 infection

Mousavi

rahmanian

Sami

2020

Infection, Genetics and Evolution

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Aims The recent outbreak of COVID-19 has become a global health concern. There are currently no effective treatment strategies and vaccines for the treatment or prevention of this fatal disease. The current study aims to determine promising treatment options for the COVID-19 through a computational drug repurposing approach. Materials and methods In this study, we focus on differentially expressed genes (DEGs), detected in SARS-CoV-2 infected cell lines including “the primary human lung epithelial cell line NHBE” and “the transformed lung alveolar cell line A549”. Next, the identified DEGs are used in the connectivity map (CMap) analysis to identify similarly acting therapeutic candidates. Furthermore, to interpret lists of DEGs, pathway enrichment and protein network analysis are performed. Genes are categorized into easily interpretable pathways based on their biological functions, and overrepresentation of each pathway is tested in comparison to what is expected randomly. Key findings The results suggest the effectiveness of lansoprazole, folic acid, sulfamonomethoxine, tolnaftate, diclofenamide, halcinonide, saquinavir, metronidazole, ebselen, lidocaine and benzocaine, histone deacetylase (HDAC) inhibitors, heat shock protein 90 (HSP90) inhibitors, and many other clinically approved drugs as potent drugs against COVID-19 outbreak. Significance Making new drugs remain a lengthy process, so the drug repurposing approach provides an insight into the therapeutics that might be helpful in this pandemic. In this study, pathway enrichment and protein network analysis are also performed, and the effectiveness of some drugs obtained from the CMap analysis has been investigated according to previous researches.

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Section: Discussionmentioning

confidence: 99%

A connectivity map-based drug repurposing study and integrative analysis of transcriptomic profiling of SARS-CoV-2 infection

Mousavi

rahmanian

Sami

2020

Infection, Genetics and Evolution

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“…Of note, in the present study, other cardiovascular medications (ie, statins, antiplatelet, warfarin, or other new oral anticoagulant drugs) used by hypertensive patients before exposure did not significantly alter the risk of COVID‐19 infection. Studies analyzing the influence of the use of these drugs and the COVID‐19 infection are scarce and mostly are focused on interactions with antiviral therapy 23,24 …”

Section: Discussionmentioning

confidence: 99%

Use of distinct anti‐hypertensive drugs and risk for COVID‐19 among hypertensive people: A population‐based cohort study in Southern Catalonia, Spain

Vila-Córcoles

Satué-Gracia

Ochoa-Gondar

et al. 2020

J of Clinical Hypertension

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The use of some anti‐hypertensive drugs in the current COVID‐19 pandemic has become controversial. This study investigated possible relationships between anti‐hypertensive medications use and COVID‐19 infection risk in the ambulatory hypertensive population. This is a population‐based retrospective cohort study involving 34 936 hypertensive adults >50 years in Tarragona (Southern Catalonia, Spain) who were retrospectively followed through pandemic period (from 01/03/2020 to 30/04/2020). Two data sets including demographic/clinical characteristics (comorbidities and cardiovascular medications use) and laboratory PCR codes for COVID‐19 were linked to construct an anonymized research database. Cox regression was used to calculate multivariable hazard ratios (HRs) and estimate the risk of suffering COVID‐19 infection. Across study period, 205 PCR‐confirmed COVID‐19 cases were observed, which means an overall incidence of 586.8 cases per 100 000 persons‐period. In multivariable analyses, only age (HR: 1.03; 95% CI: 1.02‐1.05; P < .001) and nursing home residence (HR: 19.60; 95% CI: 13.80‐27.84; P < .001) appeared significantly associated with increased risk of COVID‐19. Considering anti‐hypertensive drugs, receiving diuretics (HR: 1.22; 95% CI: 0.90‐1.67; P = .205), calcium channel blockers (HR: 1.29; 95%CI: 0.91‐1.82; P = .148), beta‐blockers (HR: 0.97; 95% CI: 0.68‐1.37; P = .844), and angiotensin‐converting enzyme inhibitors (HR: 0.83; 95% CI: 0.61‐1.13; P = .238) did not significantly alter the risk of PCR‐confirmed COVID‐19, whereas receiving angiotensin II receptor blockers was associated with an almost statistically significant reduction risk (HR: 0.67; 95% CI: 0.44‐1.01; P = .054). In conclusion, our data support that receiving renin‐angiotensin‐aldosterone system inhibitors does not predispose for suffering COVID‐19 infection in ambulatory hypertensive people. Conversely, receiving angiotensin II receptor blockers could be related with a reduced risk.

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“…Therefore, it is possible that the beneficial effects of statin therapy as an add-on treatment in viral infections could be extended to COVID-19. To this regard, it should be considered that a peculiar antiviral mechanism of action of statins against COVID-19 might consist of inhibition of SARS-CoV-2 entry into host cells due to the binding of its main protease [ 36 ]. Nonetheless, whether statin therapy may reduce the risk of SARS-CoV-2 infection still needs to be investigated.…”

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confidence: 99%

Commentary: Statins, COVID-19, and coronary artery disease: killing two birds with one stone

et al. 2020

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Statins and the COVID-19 main protease: in silico evidence on direct interaction

Cited by 248 publications

References 24 publications

A connectivity map-based drug repurposing study and integrative analysis of transcriptomic profiling of SARS-CoV-2 infection

A connectivity map-based drug repurposing study and integrative analysis of transcriptomic profiling of SARS-CoV-2 infection

Use of distinct anti‐hypertensive drugs and risk for COVID‐19 among hypertensive people: A population‐based cohort study in Southern Catalonia, Spain

Commentary: Statins, COVID-19, and coronary artery disease: killing two birds with one stone

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