Potential Therapeutic Benefits of Dipyridamole in COVID-19 Patients

Aliter, Kholoud F.; Al‐Horani, Rami A.

doi:10.2174/1381612826666201001125604

Cited by 21 publications

(14 citation statements)

References 93 publications

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“…These agents may be proved beneficial in treating complex pathologies, in which coagulation and inflammation play major roles such as sepsis, disseminated intravascular coagulation, colitis, pneumonitis, arthritis, ischemic stroke, and diabetic nephropathy (Foley & Conway, 2016). Lastly, inflammation and coagulation are important driving forces in exacerbating infectious diseases as demonstrated by the ongoing pandemic of COVID‐19 (Al‐Horani, 2020a, 2020b; Aliter & Al‐Horani, 2021a, 2021b). Thus, inhibitor 16 and similar molecules may hold a potential in treating the severe cases of COVID‐19 infection.…”

Section: Discussionmentioning

confidence: 99%

Sulfonated non‐saccharide molecules and human factor XIa: Enzyme inhibition and computational studies

et al. 2022

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Human factor XIa (FXIa) is a serine protease in the intrinsic coagulation pathway. FXIa has been actively targeted to develop new anticoagulants that are associated with a reduced risk of bleeding. Thousands of FXIa inhibitors have been reported, yet none has reached the clinic thus far. We describe here a novel class of sulfonated molecules that allosterically inhibit FXIa with moderate potency. A library of 18 sulfonated molecules was evaluated for the inhibition of FXIa using a chromogenic substrate hydrolysis assay. Only six molecules inhibited FXIa with IC50 values of 4.6–29.5 μM. Michaelis–Menten kinetics indicated that sulfonated molecules are allosteric inhibitors of FXIa. Inhibition of FXIa by these molecules was reversed by protamine. The molecules also showed moderate anticoagulant effects in human plasma with preference to prolong activated partial thromboplastin time. Their binding to an allosteric site in the catalytic domain of FXIa was modeled to illustrate potential binding mode and potential important Arg/Lys residues. Particularly, inhibitor 16 (IC50 = 4.6 µM) demonstrated good selectivity over a panel of serine proteases including those in the coagulation process. Inhibitor 16 did not significantly compromise the viability of three cell lines. Overall, the reported sulfonated molecules serve as a new platform to design selective, potent, and allosteric inhibitors of FXIa for therapeutic applications.

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Section: Discussionmentioning

confidence: 99%

Sulfonated non‐saccharide molecules and human factor XIa: Enzyme inhibition and computational studies

et al. 2022

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“…Clinical trials on administration of prostacyclin or NO in COVID-19 patients are in progress[ 117 , 118 ]. Similarly, dipyridamole, a phosphodiesterase 3 inhibitor with antiplatelet and anti-inflammatory action, could have beneficial effects in COVID-19 patients[ 119 ]. The potential therapeutic benefits are being investigated[ 120 , 121 ].…”

Section: Discussionmentioning

confidence: 99%

Acute myocardial injury in patients with COVID-19: Possible mechanisms and clinical implications

I¹,

Turlacu²,

Micheu³

2022

WJCC

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Severe acute respiratory syndrome coronavirus 2 infection affects not only the lungs, but also the cardiovascular system, having a major impact on patients’ outcomes. Myocardial injury (MI) occurs in the context of coronavirus infectious disease 2019 (COVID-19) and is associated with a higher risk of severe clinical outcome and mortality. COVID-19-related MI can have various clinical manifestations, of which the main ones are myocarditis, stress cardiomyopathy, acute coronary syndrome, and pulmonary embolism. The exact mechanisms of how MI occurs in these patients are not yet fully known. Direct injury, through direct viral myocardial invasion, and indirect injury, through interaction with angiotensin I converting enzyme 2, increased inflammation, and thrombocyte and endothelial dysfunction, could be involved in acute MI in patients with COVID-19. A better understanding of these multiple potential mechanisms may help to develop new targeted therapeutic strategies. The purpose of this review is to provide the current understanding of the potential mechanisms involved in MI induced by COVID-19 and to discuss the current progress in the therapeutic strategies.

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“…Dipyridamole was used as a component of dual antithrombotic therapy considering its potential benefits in the treatment of SARS-CoV-2 virus infection. Several publications mentioned the ability of this drug to suppress SARS-CoV-2 replication in vitro and improve the clinical course of the disease [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Off-Label Use of a Double-Layer Micromesh Carotid Stent for Hybrid Treatment of Popliteal Artery Aneurism Complicated by Chronic Distal Embolization

Barat

Casian

2021

Case Reports in Vascular Medicine

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We report our initial experience in off-label use of the double-layer micromesh (DLM) Roadsaver® stent for the hybrid treatment of a fusiform popliteal artery aneurism complicated by distal embolization and chronic limb threatening ischemia in a COVID-19-positive young male. A 36-year-old male patient was admitted with chronic limb threatening ischemia of the left lower limb. The duplex ultrasound and computer tomography angiography (CTA) demonstrated a fusiform popliteal artery aneurism with a maximal diameter of 14 mm and distal occlusion of peroneal and both tibial arteries. Urgent hybrid intervention was performed, starting with an open thrombectomy from the distal posterior tibial artery via a retromalleolar access followed by percutaneous deployment of the DLM Roadsaver® stent (Terumo, Tokyo, Japan) for the exclusion of the popliteal artery aneurism. The flow diverting effect was observed immediately with contrast stagnation in the asymmetrical part of the aneurism sac (grade C2 of the O’Kelly-Marotta flow diversion scale). The procedure was uneventful, with the regaining of an adequate foot perfusion and palpable pulse at the posterior tibial artery. On the 2nd postoperative day, the patient was diagnosed with a symptomatic form of COVID-19 infection and transferred to a dedicated facility. At a one-month follow-up, the patient had no symptoms of limb ischemia and CTA showed complete thrombosis of the aneurism sac, absence of endoleaks, and patency of the treated arterial segment. This case demonstrates the possibility of off-label use of the DLM Roadsaver® stent for hybrid treatment of popliteal artery aneurism complicated by distal embolization and critical limb ischemia.

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Potential Therapeutic Benefits of Dipyridamole in COVID-19 Patients

Cited by 21 publications

References 93 publications

Sulfonated non‐saccharide molecules and human factor XIa: Enzyme inhibition and computational studies

Sulfonated non‐saccharide molecules and human factor XIa: Enzyme inhibition and computational studies

Acute myocardial injury in patients with COVID-19: Possible mechanisms and clinical implications

Off-Label Use of a Double-Layer Micromesh Carotid Stent for Hybrid Treatment of Popliteal Artery Aneurism Complicated by Chronic Distal Embolization

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