Dipyridamole for COVID-19
Dipyridamole has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Potential SARS-CoV-2 main protease inhibitors, Drug Discovery Today, doi:10.1016/j.drudis.2020.12.005 ,
Molecular Docking Reveals the Potential of Aliskiren, Dipyridamole, Mopidamol, Rosuvastatin, Rolitetracycline and Metamizole to Inhibit COVID-19 Virus Main Protease, American Chemical Society (ACS), doi:10.26434/chemrxiv.12061302.v1 ,
Drug repurposing is a fast way to rapidly discover a drug for clinical use. In such circumstances of the spreading of the highly contagious COVID-19, searching for already known drugs is a worldwide demand. In this study, many drugs were evaluated by molecular docking. Among the test compounds, aliskiren (the best), dipyridamole, mopidamol and rosuvastatin showed higher energies of binding than that of the co-crystallized ligand N3 with COVID-19 main protease Mpro. Rolitetracycline showed the best binding with the catalytic center of the protease enzyme through binding with CYS 145 and HIS 41. Metamizole showed about 86 % of the binding energy of the ligand N3 while the protease inhibitor darunavir showed little bit lower binding energy than N3. These results are promising for using these drugs in the treatment and management of the spreading of COVID-19 virus. Also, it could stimulate clinical trials for the use of these drugs by systemic or inhalation route.The results stimulate the evaluation of these drugs as anti COVID-19 especially aliskiren which showed the highest score of binding with the binding site of N3. This will be added to its renin inhibition and advantage of renin inhibition and possibility of the reduced expression of ACE2. Dipyridamole and mopidamol showed a potential to be more Mpro inhibitor than ligand N3 and darunavir. Also, dipyridamole has the property of antiviral activity beside its use to decrease the hypercoagulabilty that happens due to COVID infection in addition to the property of promoting type I interferon (IFN) responses and protect mice from viral pneumonia . Rolitetracycling is an amazing in its binding mode in the active site of the protease pocket it seemed as it is tailored to be buried in that pocket. Mopidamol and rosuvastatin are slightly better than the co-crystallized ligand N3 and darunavir in binding mode which nominate the as COVID-19 protease inhibitors. Hopefully this study will help in the repurposing a drug for the treatment of COVID-19.
Review of trials currently testing treatment and prevention of COVID-19, Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.05.019 ,
The role of cell death in SARS-CoV-2 infection, Signal Transduction and Targeted Therapy, doi:10.1038/s41392-023-01580-8 ,
AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing high infectiousness, resulted in an ongoing pandemic termed coronavirus disease 2019 (COVID-19). COVID-19 cases often experience acute respiratory distress syndrome, which has caused millions of deaths. Apart from triggering inflammatory and immune responses, many viral infections can cause programmed cell death in infected cells. Cell death mechanisms have a vital role in maintaining a suitable environment to achieve normal cell functionality. Nonetheless, these processes are dysregulated, potentially contributing to disease pathogenesis. Over the past decades, multiple cell death pathways are becoming better understood. Growing evidence suggests that the induction of cell death by the coronavirus may significantly contributes to viral infection and pathogenicity. However, the interaction of SARS-CoV-2 with cell death, together with its associated mechanisms, is yet to be elucidated. In this review, we summarize the existing evidence concerning the molecular modulation of cell death in SARS-CoV-2 infection as well as viral-host interactions, which may shed new light on antiviral therapy against SARS-CoV-2.
Different drug approaches to COVID-19 treatment worldwide: an update of new drugs and drugs repositioning to fight against the novel coronavirus, Therapeutic Advances in Vaccines and Immunotherapy, doi:10.1177/25151355221144845 ,
According to the World Health Organization (WHO), in the second half of 2022, there are about 606 million confirmed cases of COVID-19 and almost 6,500,000 deaths around the world. A pandemic was declared by the WHO in March 2020 when the new coronavirus spread around the world. The short time between the first cases in Wuhan and the declaration of a pandemic initiated the search for ways to stop the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or to attempt to cure the disease COVID-19. More than ever, research groups are developing vaccines, drugs, and immunobiological compounds, and they are even trying to repurpose drugs in an increasing number of clinical trials. There are great expectations regarding the vaccine’s effectiveness for the prevention of COVID-19. However, producing sufficient doses of vaccines for the entire population and SARS-CoV-2 variants are challenges for pharmaceutical industries. On the contrary, efforts have been made to create different vaccines with different approaches so that they can be used by the entire population. Here, we summarize about 8162 clinical trials, showing a greater number of drug clinical trials in Europe and the United States and less clinical trials in low-income countries. Promising results about the use of new drugs and drug repositioning, monoclonal antibodies, convalescent plasma, and mesenchymal stem cells to control viral infection/replication or the hyper-inflammatory response to the new coronavirus bring hope to treat the disease.
Brequinar and dipyridamole in combination exhibits synergistic antiviral activity against SARS-CoV-2 in vitro: Rationale for a host-acting antiviral treatment strategy for COVID-19, Antiviral Research, doi:10.1016/j.antiviral.2022.105403 ,
Brequinar and Dipyridamole in Combination Exhibits Synergistic Antiviral Activity Against SARS-CoV-2 in vitro: Rationale for a host-acting antiviral treatment strategy for COVID-19, bioRxiv, doi:10.1101/2022.03.30.486499 ,
The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised the efficacy of currently available vaccines and monoclonal antibody (mAb)-based treatment options for COVID-19. The limited number of authorized small-molecule direct-acting antivirals present challenges with pill burden, the necessity for intravenous administration or potential drug interactions. There remains an unmet medical need for effective and convenient treatment options for SARS-CoV-2 infection. SARS-CoV-2 is an RNA virus that depends on host intracellular ribonucleotide pools for its replication. Dihydroorotate dehydrogenase (DHODH) is a ubiquitous host enzyme that is required for de novo pyrimidine synthesis. The inhibition of DHODH leads to a depletion of intracellular pyrimidines, thereby impacting viral replication in vitro. Brequinar (BRQ) is an orally available, selective, and potent low nanomolar inhibitor of human DHODH that has been shown to exhibit broad spectrum inhibition of RNA virus replication. However, host cell nucleotide salvage pathways can maintain intracellular pyrimidine levels and compensate for BRQ-mediated DHODH inhibition. In this report, we show that the combination of BRQ and the salvage pathway inhibitor dipyridamole (DPY) exhibits strong synergistic antiviral activity in vitro against SARS-CoV-2 by enhanced depletion of the cellular pyrimidine nucleotide pool. The combination of BRQ and DPY showed antiviral activity against the prototype SARS-CoV-2 as well as the Beta (B.1.351) and Delta (B.1.617.2) variants. These data support the continued evaluation of the combination of BRQ and DPY as a broad-spectrum, host-acting antiviral strategy to treat SARS-CoV-2 and potentially other RNA virus infections.
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