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  1. Article ; Online: Correction to: Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Additional Benefit.

    Sun, Duxin

    The AAPS journal

    2020  Volume 22, Issue 5, Page(s) 102

    Abstract: During the proofing process, the misspelling of "additional" occurred while changing the title of the article. The complete title should be "Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Additional Benefit" ...

    Abstract During the proofing process, the misspelling of "additional" occurred while changing the title of the article. The complete title should be "Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Additional Benefit".
    Keywords covid19
    Language English
    Publishing date 2020-08-02
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ISSN 1550-7416
    ISSN (online) 1550-7416
    DOI 10.1208/s12248-020-00483-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit.

    Sun, Duxin

    The AAPS journal

    2020  Volume 22, Issue 4, Page(s) 77

    Abstract: Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models ... ...

    Abstract Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5-9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. Graphical abstract.
    MeSH term(s) Adenosine Monophosphate/administration & dosage ; Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/blood ; Adenosine Monophosphate/chemistry ; Adenosine Monophosphate/therapeutic use ; Administration, Inhalation ; Administration, Intravenous ; Alanine/administration & dosage ; Alanine/analogs & derivatives ; Alanine/blood ; Alanine/chemistry ; Alanine/therapeutic use ; Animals ; Antiviral Agents/therapeutic use ; Betacoronavirus/drug effects ; COVID-19 ; Coronavirus Infections/drug therapy ; Humans ; Pandemics ; Pneumonia, Viral/drug therapy ; SARS-CoV-2
    Chemical Substances Antiviral Agents ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX)
    Keywords covid19
    Language English
    Publishing date 2020-05-26
    Publishing country United States
    Document type Journal Article
    ISSN 1550-7416
    ISSN (online) 1550-7416
    DOI 10.1208/s12248-020-00459-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Correction to

    Sun, Duxin

    The AAPS Journal

    Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Additional Benefit

    2020  Volume 22, Issue 5

    Keywords covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    ISSN 1550-7416
    DOI 10.1208/s12248-020-00483-8
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Remdesivir for Treatment of COVID-19

    Sun, Duxin

    The AAPS Journal

    Combination of Pulmonary and IV Administration May Offer Aditional Benefit

    2020  Volume 22, Issue 4

    Keywords covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    ISSN 1550-7416
    DOI 10.1208/s12248-020-00459-8
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: CoGT

    Yingzi Bu / Ruoxi Gao / Bohan Zhang / Luchen Zhang / Duxin Sun

    ACS Omega, Vol 8, Iss 14, Pp 13232-

    Ensemble Machine Learning Method and Its Application on JAK Inhibitor Discovery

    2023  Volume 13242

    Keywords Chemistry ; QD1-999
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher American Chemical Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Correction to: Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Additional Benefit

    Sun, Duxin

    AAPS J

    Abstract: During the proofing process, the misspelling of "additional" occurred while changing the title of the article. The complete title should be "Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Additional Benefit" ...

    Abstract During the proofing process, the misspelling of "additional" occurred while changing the title of the article. The complete title should be "Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Additional Benefit".
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #692702
    Database COVID19

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  7. Article: Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit

    Sun, Duxin

    AAPS J

    Abstract: Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models ... ...

    Abstract Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5-9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. Graphical abstract.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #377941
    Database COVID19

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  8. Article: Mycophenolate-mofetil/prednisone/tacrolimus

    Sun, Duxin

    Reactions Weekly

    Abstract: A 39-year-old man developed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) during treatment with mycophenolate mofetil, prednisone and tacrolimus as immunosupression therapy [routes not stated;not all dosages stated] The man with a history ... ...

    Abstract A 39-year-old man developed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) during treatment with mycophenolate mofetil, prednisone and tacrolimus as immunosupression therapy [routes not stated;not all dosages stated] The man with a history of idiopathic dilated cardiomyopathy and chronic kidney disease, and underwent combined heart/kidney transplant in 2017, presented for COVID-19 testing He had symptoms of fever, headache, dyspnoea, fatigue, sore throat, dry cough and myalgia On the nest day of the testing, he was found positive for COVID-19 As the symptoms were minimal, he was quarantined at his home On the next day, his symptoms worsened Therefore, he was advised to return to the hospital for further evaluation Previously, he had antibody-mediated cardiac graft rejection, which was being treated with methylprednisolone, plasmapheresis, IV immunoglobulin [Gamunex] and antithymocyte-globulin [rabbit anti-thymocyte globulin] He had completed this treatment approximately 8 months prior to the admission His history was significant for poorly controlled insulin-dependent diabetes mellitus, morbid obesity, hypertension and chronic diabetic foot ulcers Upon his repeat presentation, he had headache, fatigue and dyspnoea He was afebrile, normotensive and mildly tachycardic Oxygen saturation was of 97% on room air Another nasopharyngeal swab also found positive for COVID-19 Laboratory test showed elevated levels of C-reactive protein, serum lactate, D-dimer, lactate dehydrogenase and troponin I Chest x-ray (CXR) showed mild pulmonary vascular congestion Therefore, he was admitted for monitoring and supportive care Upon admission, his mycophenolate mofetil was held due to his pronounced lymphopenia However, his treatment with tacrolimus, losartan and prednisone 9mg daily kept continued On the following day, he remained afebrile with minimal dyspnoea upon exertion He was discharged as he insisted to He was advised to continue holding mycophenolate mofetil until further notice After three days, he was readmitted due to worsening of symptoms with hypoxia At admission, he was treated with paracetamol, and he became afebrile He was normotensive, tachycardic and tachypneic with an oxygen saturation of 95% on room air His D-dimer, LDH, CRP, BNP and troponin I levels were found to be elevated Therefore, his tacrolimus doses were adjusted to tacrolimus trough level of 5-8 ng/mL A severely low immune cell response was noted upon examination His treatment with tacrolimus and prednisone were continued, while his losartan and mycophenolate mofetil remained held He was started on off label hydroxychloroquine 400mg twice daily On the next day, he developed low-grade fever with hypoxia, which required 4 lpm of oxygen via nasal cannula Due to rapid respiratory decompensation, he was shifted to the ICU He was enrolled in the Adaptive COVID-19 Treatment Trial (NCT04280705) evaluating remdesivir versus placebo and started on the study drug His treatment with hydroxychloroquine was discontinued He had mild fever and chills over the next two days, which were controlled with aspirin His oxygen requirements decreased steadily A left ventricular ejection fraction was found to be normal upon transthoracic echocardiography Therefore, he was shifted to the general ward He was slowly weaned off oxygen supplementation Eventually, he was discharged
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #692703
    Database COVID19

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  9. Article ; Online: CoGT: Ensemble Machine Learning Method and Its Application on JAK Inhibitor Discovery.

    Bu, Yingzi / Gao, Ruoxi / Zhang, Bohan / Zhang, Luchen / Sun, Duxin

    ACS omega

    2023  Volume 8, Issue 14, Page(s) 13232–13242

    Abstract: The discovery of new drug candidates to inhibit an intended target is a complex and resource-consuming process. A machine learning (ML) method for predicting drug-target interactions (DTI) is a potential solution to improve the efficiency. However, ... ...

    Abstract The discovery of new drug candidates to inhibit an intended target is a complex and resource-consuming process. A machine learning (ML) method for predicting drug-target interactions (DTI) is a potential solution to improve the efficiency. However, traditional ML approaches have limitations in accuracy. In this study, we developed a novel ensemble model CoGT for DTI prediction using multilayer perceptron (MLP), which integrated graph-based models to extract non-Euclidean molecular structures and large pretrained models, specifically chemBERTa, to process simplified molecular input line entry systems (SMILES). The performance of CoGT was evaluated using compounds inhibiting four Janus kinases (JAKs). Results showed that the large pretrained model, chemBERTa, was better than other conventional ML models in predicting DTI across multiple evaluation metrics, while the graph neural network (GNN) was effective for prediction on imbalanced data sets. To take full advantage of the strengths of these different models, we developed an ensemble model, CoGT, which outperformed other individual ML models in predicting compounds' inhibition on different isoforms of JAKs. Our data suggest that the ensemble model CoGT has the potential to accelerate the process of drug discovery.
    Language English
    Publishing date 2023-03-27
    Publishing country United States
    Document type Journal Article
    ISSN 2470-1343
    ISSN (online) 2470-1343
    DOI 10.1021/acsomega.3c00160
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Why 90% of clinical drug development fails and how to improve it?

    Sun, Duxin / Gao, Wei / Hu, Hongxiang / Zhou, Simon

    Acta pharmaceutica Sinica. B

    2022  Volume 12, Issue 7, Page(s) 3049–3062

    Abstract: Ninety percent of clinical drug development fails despite implementation of many successful strategies, which raised the question whether certain aspects in target validation and drug optimization are overlooked? Current drug optimization overly ... ...

    Abstract Ninety percent of clinical drug development fails despite implementation of many successful strategies, which raised the question whether certain aspects in target validation and drug optimization are overlooked? Current drug optimization overly emphasizes potency/specificity using structure‒activity-relationship (SAR) but overlooks tissue exposure/selectivity in disease/normal tissues using structure‒tissue exposure/selectivity-relationship (STR), which may mislead the drug candidate selection and impact the balance of clinical dose/efficacy/toxicity. We propose structure‒tissue exposure/selectivity-activity relationship (STAR) to improve drug optimization, which classifies drug candidates based on drug's potency/selectivity, tissue exposure/selectivity, and required dose for balancing clinical efficacy/toxicity. Class I drugs have high specificity/potency and high tissue exposure/selectivity, which needs low dose to achieve superior clinical efficacy/safety with high success rate. Class II drugs have high specificity/potency and low tissue exposure/selectivity, which requires high dose to achieve clinical efficacy with high toxicity and needs to be cautiously evaluated. Class III drugs have relatively low (adequate) specificity/potency but high tissue exposure/selectivity, which requires low dose to achieve clinical efficacy with manageable toxicity but are often overlooked. Class IV drugs have low specificity/potency and low tissue exposure/selectivity, which achieves inadequate efficacy/safety, and should be terminated early. STAR may improve drug optimization and clinical studies for the success of clinical drug development.
    Language English
    Publishing date 2022-02-11
    Publishing country Netherlands
    Document type Journal Article ; Review
    ISSN 2211-3835
    ISSN 2211-3835
    DOI 10.1016/j.apsb.2022.02.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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