SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target
Shuofeng Yuan,Hin Chu,Jasper Fuk-Woo Chan,Zi-Wei Ye,Lei Wen,Bingpeng Yan,Pok Man Lai,Kah Meng Tee,Jingjing Huang,Dongdong Chen,Cun Li,Xiaoyu Zhao,Dong Yang,Man Chun Chiu,Cyril C. Y. Yip,Vincent Kwok-Man Poon,Chris Chung-Sing Chan,Kong-Hung Sze,Jie Zhou,Ivy Hau-Yee Chan,Kin-Hang Kok,Kelvin K. W. To,Richard Y.T. Kao,Johnson Yiu-Nam Lau,Dong-Yan Jin,Stanley Perlman,Kwok-Yung Yuen +26 more
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TLDR
This study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.Abstract:
Viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.read more
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Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2
Yadi Zhou,Yuan Hou,Jiayu Shen,Yin Huang,William R. Martin,Feixiong Cheng,Feixiong Cheng,Feixiong Cheng +7 more
TL;DR: This study presents an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV–host interactome and drug targets in the human protein–protein interaction network.
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Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing.
Laura Riva,Shuofeng Yuan,Xin Yin,Laura Martin-Sancho,Naoko Matsunaga,Lars Pache,Sebastian Burgstaller-Muehlbacher,Paul D. De Jesus,Peter Teriete,Mitchell V. Hull,Max W. Chang,Jasper Fuk-Woo Chan,Jianli Cao,Vincent Kwok-Man Poon,Kristina M. Herbert,Kuoyuan Cheng,Kuoyuan Cheng,Tu Trinh H. Nguyen,Andrey Rubanov,Yuan Pu,Courtney Nguyen,Angela Choi,Raveen Rathnasinghe,Michael Schotsaert,Lisa Miorin,Marion Dejosez,Thomas P. Zwaka,Ko Yung Sit,Luis Martinez-Sobrido,Wen-Chun Liu,Kris M. White,Mackenzie E. Chapman,Emma K. Lendy,Richard Glynne,Randy A. Albrecht,Eytan Ruppin,Andrew D. Mesecar,Jeffrey R Johnson,Christopher Benner,Ren Sun,Peter G. Schultz,Andrew I. Su,Adolfo García-Sastre,Arnab K. Chatterjee,Kwok-Yung Yuen,Sumit K. Chanda +45 more
TL;DR: A screen of the ReFRAME library of approximately 12,000 known drugs for antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identified several candidate compounds with suitable activities and pharmacological profiles, which could potentially expedite the deployment of therapies for coronav virus disease 2019 (COVID-19).
Journal ArticleDOI
Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication
Bingpeng Yan,Hin Chu,Dong Yang,Kong-Hung Sze,Pok Man Lai,Shuofeng Yuan,Huiping Shuai,Yixin Wang,Richard Y.T. Kao,Jasper Fuk-Woo Chan,Kwok-Yung Yuen +10 more
TL;DR: It is demonstrated that host lipid metabolic remodeling was significantly associated with human-pathogenic coronavirus propagation and suggested that lipid metabolism regulation would be a common and druggable target for coronav virus infections.
Journal ArticleDOI
The Role of Lipid Metabolism in COVID-19 Virus Infection and as a Drug Target.
Mohamed Abu-Farha,Thangavel Alphonse Thanaraj,Mohammad Qaddoumi,Anwar M. Hashem,Jehad Abubaker,Fahd Al-Mulla +5 more
TL;DR: The role of lipid metabolism in viral infection as well as the possibility of targeting lipid metabolism to interfere with the viral life cycle are discussed.
Journal ArticleDOI
A metabolic handbook for the COVID-19 pandemic.
TL;DR: In this Perspective, Ayres provides insight into how current knowledge of immunometabolism and metabolic diseases can inform the understanding of COVID-19 pathology, and proposes potential metabolism-based clinical solutions.
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TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.
Journal ArticleDOI
Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010
Theo Vos,Abraham D. Flaxman,Mohsen Naghavi,Rafael Lozano,Catherine Michaud,Majid Ezzati,Kenji Shibuya,Joshua A. Salomon,Safa Abdalla,Victor Aboyans,Jerry Abraham,Ilana N. Ackerman,Rakesh Aggarwal,Stephanie Y. Ahn,Mohammed K. Ali,Mohammad A. AlMazroa,Miriam Alvarado,H. Ross Anderson,Laurie M. Anderson,Kathryn G. Andrews,Charles Atkinson,Larry M. Baddour,Adil N. Bahalim,Suzanne Barker-Collo,Lope H Barrero,David Bartels,María-Gloria Basáñez,Amanda J Baxter,Michelle L. Bell,Emelia J. Benjamin,Derrick A Bennett,Eduardo Bernabé,Kavi Bhalla,Bishal Bhandari,Boris Bikbov,Aref A. Bin Abdulhak,Gretchen L. Birbeck,James A. Black,Hannah Blencowe,Jed D. Blore,Fiona M. Blyth,Ian Bolliger,Audrey Bonaventure,Soufiane Boufous,Rupert R A Bourne,Michel Boussinesq,Tasanee Braithwaite,Carol Brayne,Lisa Bridgett,Simon Brooker,Peter Brooks,Traolach S. Brugha,Claire Bryan-Hancock,Chiara Bucello,Rachelle Buchbinder,Geoffrey Buckle,Christine M. Budke,Michael Burch,Peter Burney,Roy Burstein,Bianca Calabria,Benjamin L. Campbell,Charles E. Canter,Hélène Carabin,Jonathan R. Carapetis,Loreto Carmona,Claudia Cella,Fiona J Charlson,Honglei Chen,Andrew T. A. Cheng,David Chou,Sumeet S. Chugh,Luc E. Coffeng,Steven D. Colan,Samantha M. Colquhoun,K. Ellicott Colson,John R. Condon,Myles Connor,Myles Connor,Myles Connor,Leslie T. Cooper,Matthew A. Corriere,Monica Cortinovis,Karen Courville De Vaccaro,William G. Couser,Benjamin C Cowie,Michael H. Criqui,Marita Cross,Kaustubh Dabhadkar,Manu Dahiya,Nabila Dahodwala,James Damsere-Derry,Goodarz Danaei,Adrian Davis,Diego De Leo,Louisa Degenhardt,Robert P. Dellavalle,Allyne Delossantos,Julie O. Denenberg,Sarah Derrett,Don C. Des Jarlais,Samath D Dharmaratne,Samath D Dharmaratne,Mukesh Dherani,Cesar Diaz-Torne,Helen Dolk,E. Ray Dorsey,Tim Driscoll,Herbert C. Duber,Beth E. Ebel,Karen Edmond,Alexis Elbaz,S. Ali,Holly E. Erskine,Patricia J. Erwin,Patricia Espindola,Stalin E. Ewoigbokhan,Farshad Farzadfar,Valery L. Feigin,David T. Felson,Alize J. Ferrari,Cleusa P. Ferri,Eric M. Fèvre,Mariel M. Finucane,Seth Flaxman,Louise Flood,Kyle J Foreman,Mohammad H. Forouzanfar,F.G.R. Fowkes,Richard C. Franklin,Richard C. Franklin,Marlene Fransen,Michael Freeman,Belinda J. Gabbe,Sherine E. Gabriel,Emmanuela Gakidou,Hammad A. Ganatra,Bianca Garcia,Flavio Gaspari,Richard F. Gillum,Gerhard Gmel,Richard A. Gosselin,Rebecca Grainger,Justina Groeger,Francis Guillemin,David Gunnell,R Gupta,Juanita A. Haagsma,Holly Hagan,Yara A. Halasa,Wayne Hall,Diana Haring,Josep Maria Haro,James Harrison,Rasmus Havmoeller,Roderick J. Hay,Hideki Higashi,Christopher Hill,Bruno Hoen,Howard J. Hoffman,Peter J. Hotez,Damian G Hoy,John J Huang,Sydney E. Ibeanusi,Kathryn H. Jacobsen,Spencer L. James,Deborah Jarvis,Rashmi Jasrasaria,Sudha Jayaraman,Nicole E. Johns,Jost B. Jonas,Ganesan Karthikeyan,Nicholas J Kassebaum,Norito Kawakami,Andre Keren,Jon Paul Khoo,Charles H. King,Lisa M. Knowlton,Olive Kobusingye,Olive Kobusingye,Adofo Koranteng,Rita Krishnamurthi,Ratilal Lalloo,Laura L Laslett,Tim Lathlean,Janet L Leasher,Yong Yi Lee,James Leigh,Stephen S Lim,Elizabeth S Limb,John K Lin,Michael S Lipnick,Steven E. Lipshultz,Wei Liu,Maria Loane,Summer Lockett Ohno,Ronan A Lyons,Jixiang Ma,Jacqueline Mabweijano,Michael F. MacIntyre,Reza Malekzadeh,Leslie Mallinger,Sivabalan Manivannan,Wagner Marcenes,Lyn March,David J. Margolis,Guy B. Marks,Robin Marks,Akira Matsumori,Richard Matzopoulos,Richard Matzopoulos,Bongani M. Mayosi,John H. McAnulty,Mary M. McDermott,Neil McGill,John J. McGrath,María Elena Medina-Mora,Michele Meltzer,Ziad A. Memish,George A. Mensah,Tony R. Merriman,Ana-Claire Meyer,Valeria Miglioli,Matthew J. Miller,Ted R. Miller,Philip B. Mitchell,Ana Olga Mocumbi,Terrie E. Moffitt,Ali A. Mokdad,Lorenzo Monasta,Marcella Montico,Maziar Moradi-Lakeh,Andrew E. Moran,Lidia Morawska,Rintaro Mori,Michele E. Murdoch,Michael K Mwaniki,Kovin Naidoo,M. Nathan Nair,Luigi Naldi,K.M. Venkat Narayan,Paul K. Nelson,Robert G. Nelson,Michael C. Nevitt,Charles R. Newton,Sandra Nolte,Paul Norman,Rosana E. Norman,Martin O'Donnell,Simon J. O’Hanlon,Casey Olives,Saad B. Omer,Katrina F Ortblad,Richard H. Osborne,Doruk Ozgediz,Andrew Page,Bishnu Pahari,Jeyaraj D Pandian,Andrea Panozo Rivero,Scott B. Patten,Neil Pearce,Rogelio Perez Padilla,Fernando Perez-Ruiz,Norberto Perico,Konrad Pesudovs,David Phillips,Michael R. Phillips,Kelsey Pierce,Sébastien D. S. Pion,Guilherme V. Polanczyk,Suzanne Polinder,C. Arden Pope,Svetlana Popova,Esteban Porrini,Farshad Pourmalek,Martin Prince,Rachel L. Pullan,Kapa D. Ramaiah,Dharani Ranganathan,Homie Razavi,Mathilda Regan,Jürgen Rehm,David B. Rein,G. Remuzzi,Kathryn Richardson,Frederick P. Rivara,Thomas Roberts,Carolyn Robinson,Felipe Rodriguez De Leòn,Luca Ronfani,Robin Room,Lisa C. Rosenfeld,Lesley Rushton,Ralph L. Sacco,Sukanta Saha,Uchechukwu Sampson,Lidia Sanchez-Riera,Ella Sanman,David C. Schwebel,James Scott,Maria Segui-Gomez,Saeid Shahraz,Donald S. Shepard,Hwashin Shin,Rupak Shivakoti,Donald H. Silberberg,David Singh,Gitanjali M Singh,Jasvinder A. Singh,Jessica Singleton,David A. Sleet,Karen Sliwa,Emma Smith,Jennifer L. Smith,Nicolas J. C. Stapelberg,Andrew C Steer,Timothy J. Steiner,Wilma A. Stolk,Lars Jacob Stovner,Christopher R. Sudfeld,Sana Syed,Giorgio Tamburlini,Mohammad Tavakkoli,Hugh R. Taylor,Jennifer A. Taylor,William J. Taylor,Bernadette Thomas,W. Murray Thomson,George D. Thurston,Imad M. Tleyjeh,Marcello Tonelli,Jeffrey A. Towbin,Thomas Truelsen,Miltiadis K. Tsilimbaris,Clotilde Ubeda,Eduardo A. Undurraga,Marieke J. van der Werf,Jim van Os,Monica S. Vavilala,Narayanaswamy Venketasubramanian,Mengru Wang,Wenzhi Wang,Kerrianne Watt,David Weatherall,Martin A. Weinstock,Robert G. Weintraub,Marc G. Weisskopf,Myrna M. Weissman,Richard A. White,Harvey Whiteford,Steven T. Wiersma,James D. Wilkinson,Hywel C Williams,Sean R.M. Williams,Emma Witt,Frederick Wolfe,Anthony D. Woolf,Sarah Wulf,Pon Hsiu Yeh,Anita K. M. Zaidi,Zhi Jie Zheng,David Zonies,Alan D. Lopez,Christopher J L Murray +363 more
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.
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