Potential antiviral properties of antiplatelet agents against SARS-CoV-2 infection: an in silico perspective

Abosheasha, Mohammed A.; El‐Gowily, Afnan H.; Elfiky, Abdo A.

doi:10.1007/s11239-021-02558-5

Cited by 8 publications

(7 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tranilast, an old anti-allergy clinical drug is a direct NLRP3 inhibitor that has entered clinical trials for the treatment of COVID-19 patients (229). Ticagrelor, an orally administered selective reversible P2Y 12 receptor antagonist, preventing P2Y 12 and ADP mediated platelet activation and aggregation has been approved for prevention of severe cardiovascular events and may be suited for sepsis-induced coagulopathy in COVID-19 (230) especially since in silico analysis suggests ticagrelor also bound the main protease and spike proteins of SARS-CoV-2 (231). Preliminary trials of prehospital antiplatelet therapy in patients with COVID-19 was associated with modest yet significantly lower in-hospital mortality (232).…”

Section: Discussionmentioning

confidence: 99%

The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2

2022

View full text Add to dashboard Cite

A long-shared evolutionary history is congruent with the multiple roles played by purinergic signaling in viral infection, replication and host responses that can assist or hinder viral functions. An overview of the involvement of purinergic signaling among a range of viruses is compared and contrasted with what is currently understood for SARS-CoV-2. In particular, we focus on the inflammatory and antiviral responses of infected cells mediated by purinergic receptor activation. Although there is considerable variation in a patient’s response to SARS-CoV-2 infection, a principle immediate concern in Coronavirus disease (COVID-19) is the possibility of an aberrant inflammatory activation causing diffuse lung oedema and respiratory failure. We discuss the most promising potential interventions modulating purinergic signaling that may attenuate the more serious repercussions of SARS-CoV-2 infection and aspects of their implementation.

show abstract

Section: Discussionmentioning

confidence: 99%

The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2

2022

View full text Add to dashboard Cite

show abstract

“…Cilostazol’s potential activity has been studied in silico. Cilostazol can bind to the SARS-CoV-2’s main protease, as well as to the spike protein [ 94 , 95 ]. Despite cilostazol’s likely clinical potential [ 96 ], there are no published data on beneficial effects in patients with COVID-19.…”

Section: Covid-19 Treatments That Target the Endothelium Or Endotheli...mentioning

confidence: 99%

The Endothelium and COVID-19: An Increasingly Clear Link Brief Title: Endotheliopathy in COVID-19

Six

Guillaume

Jacob

et al. 2022

IJMS

View full text Add to dashboard Cite

The endothelium has a fundamental role in the cardiovascular complications of coronavirus disease 2019 (COVID-19). Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particularly affects endothelial cells. The virus binds to the angiotensin-converting enzyme 2 (ACE-2) receptor (present on type 2 alveolar cells, bronchial epithelial cells, and endothelial cells), and induces a cytokine storm. The cytokines tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 have particular effects on endothelial cells—leading to endothelial dysfunction, endothelial cell death, changes in tight junctions, and vascular hyperpermeability. Under normal conditions, apoptotic endothelial cells are removed into the bloodstream. During COVID-19, however, endothelial cells are detached more rapidly, and do not regenerate as effectively as usual. The loss of the endothelium on the luminal surface abolishes all of the vascular responses mediated by the endothelium and nitric oxide production in particular, which results in greater contractility. Moreover, circulating endothelial cells infected with SARS-CoV-2 act as vectors for viral dissemination by forming clusters that migrate into the circulation and reach distant organs. The cell clusters and the endothelial dysfunction might contribute to the various thromboembolic pathologies observed in COVID-19 by inducing the formation of intravascular microthrombi, as well as by triggering disseminated intravascular coagulation. Here, we review the contributions of endotheliopathy and endothelial-cell-derived extracellular vesicles to the pathogenesis of COVID-19, and discuss therapeutic strategies that target the endothelium in patients with COVID-19.

show abstract

“…127,128 Other studies targeted endosomes to inhibit coronavirus-2 infection. 129 It has also been discovered that endosomal acidification factors, such as bafilomycin A1, inhibit endosomal SARS-CoV-2 via the CLIC/GEEC endocytic pathway, which is pH dependent 3 8) and eventually virus assembly (9) and maturation (10) then viral release (11).…”

Section: Endocytic Proteins As Antiviral Targets Against Sars-cov-2 E...mentioning

confidence: 99%

“…The rapid appearance and transmission of new SARS‐CoV‐2 variants as well as the associated high mortality rate have imposed more challenges on research communities to modify existing detection methods and therapeutic protocols. 8 , 9 , 10 , 11 Although vaccination strategies have become the gold standard for preventing SARS‐CoV‐2 infections, challenges have emerged because of mutational variants gaining increased infectivity potential and becoming less responsive to vaccines. 12 , 13 Recent studies compared the titer of neutralizing antibodies of natural SARS‐CoV‐2 infection and Sinovac vaccination to evaluate the efficacy of vaccination.…”

Section: Introductionmentioning

confidence: 99%

“…The recent SARS‐CoV‐2 pandemic, with its associated high mortality rate, elicited tremendous research efforts to explore the biology, viral–host cell interactions, and screening methods for the virus and to suggest therapeutic approaches via either vaccination or the use of antiviral drugs. The rapid appearance and transmission of new SARS‐CoV‐2 variants as well as the associated high mortality rate have imposed more challenges on research communities to modify existing detection methods and therapeutic protocols 8–11 . Although vaccination strategies have become the gold standard for preventing SARS‐CoV‐2 infections, challenges have emerged because of mutational variants gaining increased infectivity potential and becoming less responsive to vaccines 12,13 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Insight into the role of clathrin‐mediated endocytosis inhibitors in SARS‐CoV‐2 infection

AlKafaas

Abdallah

Ghosh

et al. 2022

Reviews in Medical Virology

View full text Add to dashboard Cite

Emergence of SARS‐CoV‐2 variants warrants sustainable efforts to upgrade both the diagnostic and therapeutic protocols. Understanding the details of cellular and molecular basis of the virus–host cell interaction is essential for developing variant‐independent therapeutic options. The internalization of SARS‐CoV‐2, into lung epithelial cells, is mediated by endocytosis, especially clathrin‐mediated endocytosis (CME). Although vaccination is the gold standard strategy against viral infection, selective inhibition of endocytic proteins, complexes, and associated adaptor proteins may present a variant‐independent therapeutic strategy. Although clathrin and/or dynamins are the most important proteins involved in CME, other endocytic mechanisms are clathrin and/or dynamin independent and rely on other proteins. Moreover, endocytosis implicates some subcellular structures, like plasma membrane, actin and lysosomes. Also, physiological conditions, such as pH and ion concentrations, represent an additional factor that mediates these events. Accordingly, endocytosis related proteins are potential targets for small molecules that inhibit endocytosis‐mediated viral entry. This review summarizes the potential of using small molecules, targeting key proteins, participating in clathrin‐dependent and ‐independent endocytosis, as variant‐independent antiviral drugs against SARS‐CoV‐2 infection. The review takes two approaches. The first outlines the potential role of endocytic inhibitors in preventing endocytosis‐mediated viral entry and its mechanism of action, whereas in the second computational analysis was implemented to investigate the selectivity of common inhibitors against endocytic proteins in SARS‐CoV‐2 endocytosis. The analysis revealed that remdesivir, methyl‐β‐cyclodextrin, rottlerin, and Bis‐T can effectively inhibit clathrin, HMG‐CoA reductase, actin, and dynamin I GTPase and are more potent in inhibiting SARS‐CoV‐2 than chloroquine. CME inhibitors for SARS‐CoV‐2 infection remain understudied.

show abstract

Potential antiviral properties of antiplatelet agents against SARS-CoV-2 infection: an in silico perspective

Cited by 8 publications

References 48 publications

The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2

The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2

The Endothelium and COVID-19: An Increasingly Clear Link Brief Title: Endotheliopathy in COVID-19

Insight into the role of clathrin‐mediated endocytosis inhibitors in SARS‐CoV‐2 infection

Contact Info

Product

Resources

About