Montelukast and Telmisartan as Inhibitors of SARS-CoV-2 Omicron Variant

Mulgaonkar, Nirmitee; Wang, Haoqi; Zhang, Junrui; Roundy, Christopher M.; Tang, Wendy; Chaki, Sankar P.; Pauvolid‐Corrêa, Alex; Hamer, Gabriel L.; Fernando, Sandun

doi:10.3390/pharmaceutics15071891

Cited by 4 publications

(2 citation statements)

References 65 publications

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“…We have screened the anti-AD and anti-diabetic drugs (either already marketed or in clinical trials) against their ability to bind to and inhibit the LPAR receptor activity, the SPIKE protein, and interfere with LPAR-SPIKE protein interaction. Identifying SPIKE protein inhibitors is important, as they directly target a key component of the virus's entry and replication process 84 . Throughout the screening, it was observed that the anti-AD drugs, including Lupron, Nilotinib, Telmisartan, CORT108297, neflamapimod, and bromocriptine, displayed a better binding affinity with the LPARs, the SPIKE, and hinder LPARs-SPIKE protein complex than the standard compounds.…”

Section: Discussionmentioning

confidence: 99%

Network analysis-guided drug repurposing strategies targeting LPAR receptor in the interplay of COVID, Alzheimer’s, and diabetes

Malar,

Verma,

Prasanth

et al. 2024

Sci Rep

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The COVID-19 pandemic caused by the SARS-CoV-2 virus has greatly affected global health. Emerging evidence suggests a complex interplay between Alzheimer’s disease (AD), diabetes (DM), and COVID-19. Given COVID-19’s involvement in the increased risk of other diseases, there is an urgent need to identify novel targets and drugs to combat these interconnected health challenges. Lysophosphatidic acid receptors (LPARs), belonging to the G protein-coupled receptor family, have been implicated in various pathological conditions, including inflammation. In this regard, the study aimed to investigate the involvement of LPARs (specifically LPAR1, 3, 6) in the tri-directional relationship between AD, DM, and COVID-19 through network analysis, as well as explore the therapeutic potential of selected anti-AD, anti-DM drugs as LPAR, SPIKE antagonists. We used the Coremine Medical database to identify genes related to DM, AD, and COVID-19. Furthermore, STRING analysis was used to identify the interacting partners of LPAR1, LPAR3, and LPAR6. Additionally, a literature search revealed 78 drugs on the market or in clinical studies that were used for treating either AD or DM. We carried out docking analysis of these drugs against the LPAR1, LPAR3, and LPAR6. Furthermore, we modeled the LPAR1, LPAR3, and LPAR6 in a complex with the COVID-19 spike protein and performed a docking study of selected drugs with the LPAR-Spike complex. The analysis revealed 177 common genes implicated in AD, DM, and COVID-19. Protein–protein docking analysis demonstrated that LPAR (1,3 & 6) efficiently binds with the viral SPIKE protein, suggesting them as targets for viral infection. Furthermore, docking analysis of the anti-AD and anti-DM drugs against LPARs, SPIKE protein, and the LPARs-SPIKE complex revealed promising candidates, including lupron, neflamapimod, and nilotinib, stating the importance of drug repurposing in the drug discovery process. These drugs exhibited the ability to bind and inhibit the LPAR receptor activity and the SPIKE protein and interfere with LPAR-SPIKE protein interaction. Through a combined network and targeted-based therapeutic intervention approach, this study has identified several drugs that could be repurposed for treating COVID-19 due to their expected interference with LPAR(1, 3, and 6) and spike protein complexes. In addition, it can also be hypothesized that the co-administration of these identified drugs during COVID-19 infection may not only help mitigate the impact of the virus but also potentially contribute to the prevention or management of post-COVID complications related to AD and DM.

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Section: Discussionmentioning

confidence: 99%

Network analysis-guided drug repurposing strategies targeting LPAR receptor in the interplay of COVID, Alzheimer’s, and diabetes

Malar,

Verma,

Prasanth

et al. 2024

Sci Rep

View full text Add to dashboard Cite

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“…The Bio-Layer Interferometry experiment results indicate a K D of 3.892 mM for the interaction between the S protein and montelukast. However, different articles present diverse perspectives on the binding site. ,, Due to the lack of crystal structure data for the S protein and montelukast, the binding site cannot be conclusively determined. Clinical studies report that elderly asthmatic patients receiving montelukast demonstrated a significant reduction in SARS-CoV-2 infections compared to those not treated with montelukast .…”

Section: Dual-target Inhibitors Of Sars-cov-2mentioning

confidence: 99%

New Strategies for Responding to SARS-CoV-2: The Present and Future of Dual-Target Drugs

Zhang,

Xiao,

et al. 2024

J. Med. Chem.

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The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of deaths, posing a serious threat to public health and safety. Rapid mutations of SARS-CoV-2 and complex interactions among multiple targets during infection pose a risk of expiry for small molecule inhibitors. This suggests that the traditional concept of "one bug, one drug" could be ineffective in dealing with the coronavirus. The dual-target drug strategy is expected to be the key to ending coronavirus infections. However, the lack of design method and improper combination of dual-targets poses obstacle to the discovery of new dual-target drugs. In this Perspective, we summarized the profiles concerning drug design methods, structure−activity relationships, and pharmacological parameters of dual-target drugs for the treatment of COVID-19. Importantly, we underscored how target combination and rational drug design illuminate the development of dualtarget drugs for SARS-CoV-2. ■ SIGNIFICANCE• This is the first Perspective on dual-target drugs for treating coronavirus. • Dual-target drugs, acting on multiple pathways, offer enhanced efficacy and can delay resistance compared to single-target treatments. • Drug repurposing for dual-target design can significantly shorten the timeline for clinical trials, addressing urgent medication needs during the early COVID-19 outbreak. • The introduction of covalent warheads can compensate for active site similarity issues, aiding in the development of high-affinity dual-target inhibitors.

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The Discovery of inhibitors of the SARS-CoV-2 S protein through computational drug repurposing

Avilés-Alía,

Zulaica,

Perez

et al. 2024

Computers in Biology and Medicine

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Montelukast and Telmisartan as Inhibitors of SARS-CoV-2 Omicron Variant

Cited by 4 publications

References 65 publications

Network analysis-guided drug repurposing strategies targeting LPAR receptor in the interplay of COVID, Alzheimer’s, and diabetes

Network analysis-guided drug repurposing strategies targeting LPAR receptor in the interplay of COVID, Alzheimer’s, and diabetes

New Strategies for Responding to SARS-CoV-2: The Present and Future of Dual-Target Drugs

The Discovery of inhibitors of the SARS-CoV-2 S protein through computational drug repurposing

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