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  1. Article ; Online: Transconjunctival lower eyelid blepharoplasty with fat transposition above the orbicularis muscle for improvement of the tear trough deformity.

    Majidian Ba, Mandy / Kolli Bs, Hiren / Moy Md, Ronald L

    Journal of cosmetic dermatology

    2021  Volume 20, Issue 9, Page(s) 2911–2916

    Abstract: Background: The tear trough is the hollow concavity of the medial lower eyelid. Surgery can address tear trough deformities and reverse visible signs of periorbital aging. The previous methods of transconjunctival blepharoplasty with fat transposition ... ...

    Abstract Background: The tear trough is the hollow concavity of the medial lower eyelid. Surgery can address tear trough deformities and reverse visible signs of periorbital aging. The previous methods of transconjunctival blepharoplasty with fat transposition were first described with subperiosteal placement of fat (Plast Reconstr Surg, 125, 2010,699, Aesthetic Surg J, 32, 2012, 426). This was followed by techniques with submuscular transposition of fat, which overcame certain difficulties associated with the subperiosteal methods (Clin Plast Surg, 20, 1993, 393, Arch Facial Plast Surg, 2, 2000, 16).
    Objectives: We present a detailed description, evaluate the efficacy, safety, and advantages of transconjunctival blepharoplasty with fat pedicle transposition above the orbicularis muscle for lower eyelid rejuvenation and improvement of the tear trough deformity.
    Methods: Forty-one patients underwent lower eyelid blepharoplasty with fat transposition above the orbicularis muscle. Clinical and photographic documentation along with patient satisfaction ratings were evaluated for a minimum of 44 months postoperatively.
    Results: Significant improvements of lower eyelid aesthetics and correction of tear trough abnormalities were observed in most patients. At 44 months postoperatively, surgical correction was maintained in all patients with a high satisfaction and long-term survival. No contour irregularities or significant long-term complications were detected in any of the patients.
    Conclusion: Transconjunctival blepharoplasty with the fat pedicle transposition placed above the orbicularis muscle is a safe and effective technique for lower eyelid rejuvenation. Compared to previously described techniques of repositioning fat into the subperiosteal or submuscular plane, this technique of transposing fat above the orbicularis muscle is an alternative technique resulting in long-term improvement of tear trough abnormalities with no major complications.
    MeSH term(s) Adipose Tissue/surgery ; Blepharoplasty ; Eyelids/surgery ; Humans ; Muscles ; Rejuvenation ; Skin Transplantation
    Language English
    Publishing date 2021-02-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2280551-5
    ISSN 1473-2165 ; 1473-2130
    ISSN (online) 1473-2165
    ISSN 1473-2130
    DOI 10.1111/jocd.13978
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Discovery of SARS-CoV-2 papain-like protease inhibitors through a combination of high-throughput screening and FlipGFP-based reporter assay.

    Xia, Zilei / Sacco, Michael Dominic / Ma, Chunlong / Townsend, Julia Alma / Kitamura, Naoya / Hu, Yanmei / Ba, Mandy / Szeto, Tommy / Zhang, Xiujun / Meng, Xiangzhi / Zhang, Fushun / Xiang, Yan / Marty, Michael Thomas / Chen, Yu / Wang, Jun

    bioRxiv : the preprint server for biology

    2021  

    Abstract: The papain-like protease ( ... ...

    Abstract The papain-like protease (PL
    Language English
    Publishing date 2021-03-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.03.15.435551
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Discovery of SARS-CoV-2 Papain-like Protease Inhibitors through a Combination of High-Throughput Screening and a FlipGFP-Based Reporter Assay.

    Ma, Chunlong / Sacco, Michael Dominic / Xia, Zilei / Lambrinidis, George / Townsend, Julia Alma / Hu, Yanmei / Meng, Xiangzhi / Szeto, Tommy / Ba, Mandy / Zhang, Xiujun / Gongora, Maura / Zhang, Fushun / Marty, Michael Thomas / Xiang, Yan / Kolocouris, Antonios / Chen, Yu / Wang, Jun

    ACS central science

    2021  Volume 7, Issue 7, Page(s) 1245–1260

    Abstract: The papain-like protease ( ... ...

    Abstract The papain-like protease (PL
    Language English
    Publishing date 2021-06-18
    Publishing country United States
    Document type Journal Article
    ISSN 2374-7943
    ISSN 2374-7943
    DOI 10.1021/acscentsci.1c00519
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Expedited Approach toward the Rational Design of Noncovalent SARS-CoV-2 Main Protease Inhibitors.

    Kitamura, Naoya / Sacco, Michael Dominic / Ma, Chunlong / Hu, Yanmei / Townsend, Julia Alma / Meng, Xiangzhi / Zhang, Fushun / Zhang, Xiujun / Ba, Mandy / Szeto, Tommy / Kukuljac, Adis / Marty, Michael Thomas / Schultz, David / Cherry, Sara / Xiang, Yan / Chen, Yu / Wang, Jun

    Journal of medicinal chemistry

    2021  Volume 65, Issue 4, Page(s) 2848–2865

    Abstract: The main protease ( ... ...

    Abstract The main protease (M
    MeSH term(s) Animals ; Antiviral Agents/chemical synthesis ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; COVID-19/metabolism ; Chlorocebus aethiops ; Coronavirus 3C Proteases/antagonists & inhibitors ; Coronavirus 3C Proteases/isolation & purification ; Coronavirus 3C Proteases/metabolism ; Cysteine Proteinase Inhibitors/chemical synthesis ; Cysteine Proteinase Inhibitors/chemistry ; Cysteine Proteinase Inhibitors/pharmacology ; Dose-Response Relationship, Drug ; Drug Design ; Humans ; Microbial Sensitivity Tests ; Models, Molecular ; Molecular Structure ; Proline/analogs & derivatives ; Proline/chemical synthesis ; Proline/chemistry ; Proline/pharmacology ; Pyrrolidines/chemical synthesis ; Pyrrolidines/chemistry ; Pyrrolidines/pharmacology ; SARS-CoV-2/drug effects ; SARS-CoV-2/enzymology ; Sulfonic Acids/chemical synthesis ; Sulfonic Acids/chemistry ; Sulfonic Acids/pharmacology ; Vero Cells ; COVID-19 Drug Treatment
    Chemical Substances Antiviral Agents ; Cysteine Proteinase Inhibitors ; Pyrrolidines ; Sulfonic Acids ; N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide (89BT58KELH) ; Proline (9DLQ4CIU6V) ; 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28) ; GC376 (H1NMJ5XDG5)
    Language English
    Publishing date 2021-04-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.1c00509
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Discovery of SARS-CoV-2 papain-like protease inhibitors through a combination of high-throughput screening and FlipGFP-based reporter assay

    Xia, Zilei / Sacco, Michael / Ma, Chunlong / Townsend, Julia / Kitamura, Naoya / Hu, Yanmei / Ba, Mandy / Szeto, Tommy / Zhang, Xiujun / Meng, Xiangzhi / Zhang, Fushun / Xiang, Yan / Marty, Michael / Chen, Yu / Wang, Jun

    bioRxiv

    Abstract: The papain-like protease (PLpro) of SARS-CoV-2 is a validated antiviral drug target. PLpro is involved in the cleavage of viral polyproteins and antagonizing host innate immune response through its deubiquitinating and deISG15ylating activities, ... ...

    Abstract The papain-like protease (PLpro) of SARS-CoV-2 is a validated antiviral drug target. PLpro is involved in the cleavage of viral polyproteins and antagonizing host innate immune response through its deubiquitinating and deISG15ylating activities, rendering it a high profile antiviral drug target. Through a FRET-based high-throughput screening, several hits were identified as PLpro inhibitors with IC50 values at the single-digit micromolar range. Subsequent lead optimization led to potent inhibitors with IC50 values ranging from 0.56 to 0.90 micromolar. To help prioritize lead compounds for the cellular antiviral assay against SARS-CoV-2, we developed the cell-based FlipGFP assay that is suitable for quantifying the intracellular enzymatic inhibition potency of PLpro inhibitors in the BSL-2 setting. Two compounds selected from the FlipGFP-PLpro assay, Jun9-53-2 and Jun9-72-2, inhibited SARS-CoV-2 replication in Caco-2 hACE2 cells with EC50 values of 8.89 and 8.32 micromolar, respectively, which were 3-fold more potent than GRL0617 (EC50 = 25.1 micromolar). The X-ray crystal structures of PLpro in complex with GRL0617 showed that binding of GRL0617 to SARS-CoV-2 induced a conformational change in the BL2 loop to the more closed conformation. Overall, the PLpro inhibitors identified in this study represent promising starting points for further development as SARS-CoV-2 antivirals, and FlipGFP-PLpro assay might be a suitable surrogate for screening PLpro inhibitors in the BSL-2 setting.
    Keywords covid19
    Language English
    Publishing date 2021-03-16
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2021.03.15.435551
    Database COVID19

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