Thapsigargin (TG): Muaj peev xwm tiv thaiv kab mob qog noj ntshav thiab Broad-spectrum Anti-viral Agent uas yuav muaj txiaj ntsig tiv thaiv SARS-CoV-2

Cov nroj tsuag muab tau tus neeg sawv cev, Thapsigargin (TG) tau siv rau hauv cov tshuaj ib txwm siv ntev. TG tau pom cov lus cog tseg tias yog cov tshuaj tiv thaiv kab mob qog noj ntshav vim tias nws cov khoom siv roj ntsha tuaj yeem cuam tshuam cov sarcoplasmic / endoplasmic reticulum Ca2 + ATPase (SERCA) twj tso kua mis uas tsim nyog rau lub xovtooj ntawm tes ua haujlwm tau zoo. Nws prodrug tau ua tiav theem 1 ntawm kev sim tshuaj. Raws li tsab ntawv tshaj tawm kev tshawb fawb tshiab, TG tau qhia dav dav cov cuab yeej tiv thaiv kab mob tiv thaiv ntau yam kab mob tib neeg hauv kev sim ua ntej. Cov txiaj ntsig tau qhia tias TG tuaj yeem siv los ua tus inhibitor tiv thaiv SARS-CoV-2, tus kab mob tshiab tshiab ua lub luag haujlwm rau COVID-19.  

Thapsigargin (TG), cov nroj tsuag muab tau los ntawm cov nroj tsuag Thapsia garganica (Apiaceae) uas yog nyob rau hauv Mediterranean. Cov nroj tsuag muaj tshuaj lom heev rau nyuj thiab yaj thiab yog li hu ua 'Carrots tuag'. Cov resins muab tau los ntawm cov nroj tsuag no tau siv rau hauv cov tshuaj ib txwm siv rau ntau yam mob rau ntau pua xyoo.  

Cov cuab yeej cytotoxic ntawm thapsigargin yog vim nws lub peev xwm los cuam tshuam sarcoplasmic / endoplasmic reticulum Ca2 + ATPase (SERCA) twj tso kua mis yog li ua rau lub hlwb tsis tuaj yeem siv tau. Qhov no ua rau TG muaj peev xwm tiv thaiv kab mob ⁽¹⁾. Nws cov prodrug Mipsagargin tau ua tiav theem 1 ntawm kev sim tshuaj tab sis tseem tsis tau tshaj tawm cov txiaj ntsig. ⁽²⁾.  

Ntawm cov qib uas tsis yog-cytotoxic, thapsigargin pom tias muaj cov cuab yeej tiv thaiv kab mob tiv thaiv kab mob khaub thuas A kab mob hauv cov qauv tsiaj. ⁽³⁾. Kev tshawb fawb ntxiv tau pom tias TG yuav ua tau zoo tiv thaiv tus kab mob ua pa syncytial (RSV), kab mob khaub thuas OC43, SARS-Cov-2 thiab tus kab mob khaub thuas A nyob rau hauv tib neeg lub hlwb, yog li ua thapsigargin muaj peev xwm dav-pom anti-viral tus neeg sawv cev rau kev kho mob ntawm cov kab mob hauv tib neeg ⁽⁴⁾. Qhov kev txhim kho no muab cov cuab yeej tshiab los daws qhov COVID-19 tshwm sim los ntawm tus kab mob SARS-CoV-2 thiab tseem ceeb heev rau qhov pom ntawm qhov xwm txheej nyuaj uas nthuav tawm los ntawm kev sib kis. ^(4,5). Txawm li cas los xij, nws yuav tsum tau mus ntsib kws kho mob yuav tsum tau ua kom tau raws li cov qauv kev nyab xeeb thiab kev ua tau zoo, ua ntej txiav txim siab rau nws siv los kho cov neeg mob COVID-19.   

Yav dhau los, BX795 tau pom muaj peev xwm ua tus kab mob dav dav rau kev siv tib neeg ⁽⁶⁾. BX795 ua los ntawm inhibiting protein kinase B (AKT) phosphorylation thiab tom qab hyperphosphorylation ntawm 4EBP1. Nws tau pom cov cuab yeej tiv thaiv kab mob tiv thaiv kab mob herpes simplex (HSV) thiab kuj tau pom tias muaj kev cuam tshuam cov lus teb inflammatory ⁽⁷⁾. Txawm li cas los xij, tsis muaj kev sim tshuaj ntsuam xyuas zoo li tab tom ua rau tus neeg sawv cev no coj nws mus tom ntej. Tsis ntev los no, tseem muaj lwm tus neeg sawv cev. diABZI (tus STING agonist) tau qhia cov cuab yeej tiv thaiv kab mob tiv thaiv tus kabmob coronavirus ⁽⁸⁾.  

Cov molecules no qhia tau tias muaj kev cia siab zoo li cov tshuaj tiv thaiv kab mob dav dav hauv kev kho mob Covid-19. Txawm li cas los xij, txhua qhov no yuav tsum tau ua raws li qhov yuav tsum tau ua hauv kev sim tshuaj los ua pov thawj lawv txoj kev nyab xeeb thiab kev ua tau zoo ua ntej raug pom zoo siv rau tib neeg los ua tshuaj. 

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References:  

1. Jaskulska A., Janecka AE., thiab Gach-Janczak K., 2020. Thapsigargin—From Traditional Medicine to Anticancer Drug. Int. J. Mol. Sci. 2021, 22(1), 4; Published: 22 December 2020. DOI: https://doi.org/10.3390/ijms22010004 

2. ClinicalTrials.gov 2015. Dose-Escalation Phase 1 Study of G-202 (Mipsagargin) in Patients With Advanced Solid Tumors. ClinicalTrials.gov Identifier: NCT01056029. Muaj nyob rau https://clinicaltrials.gov/ct2/show/NCT01056029 Tau txais los ntawm 03 Lub Ob Hlis 2021.  

3. Goulding LV., Yang J., et al 2020. Thapsigargin ntawm Non-Cytotoxic Levels Induces a Potent Host Antiviral Response that Blocks Influenza A Virus Replication. Kab mob 2020, 12(10), 1093; Published: 27 September 2020. DOI: https://doi.org/10.3390/v12101093 

4. Al-Beltagi S., Preda CA., 2021. Thapsigargin Yog Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus. Kab mob 2021, 13(2), 234. Published: 3 February 2021. DOI: https://doi.org/10.3390/v13020234 

5. Tsev Kawm Ntawv Qib Siab Nottingham 2021. Xov Xwm - Cov kws tshawb fawb nthuav tawm cov tshuaj tiv thaiv kab mob rau Covid-19. Tshaj tawm 03 Lub Ob Hlis 2021. Muaj nyob online ntawm  https://www.nottingham.ac.uk/news/thapsigargin-covid-19 

6. Jaishankar thiab al. 2018. Ib qho kev tawm tsam ntawm BX795 blocks herpes simplex virus type 1 infection of the eye. Science Translational Tshuaj. 10 (428). https://doi.org/10.1126/scitranslmed.aan5861 

7. Yu t., Wang ZW., thiab al 2020. Lub kinase inhibitor BX795 suppresses inflammatory teb ntawm ntau kinases. Biochemical Pharmacology Volume 174, Plaub Hlis Ntuj 2020, 113797. Luam tawm 10 Lub Ib Hlis 2020. DOI: https://doi.org/10.1016/j.bcp.2020.113797 

8. Zhu Q., Zhang Y., 2021. Inhibition of coronavirus infection by a synthetic STING agonist in the first human airway system. Antiviral Research Volume 187, Peb Hlis 2021, 105015. Luam tawm 12 Lub Ib Hlis 2021. DOI: https://doi.org/10.1016/j.antiviral.2021.105015 

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