Inhibition of SARS-CoV-2 entry through the ACE2/TMPRSS2 pathway: a promising approach for uncovering early COVID-19 drug therapies

European Journal of Clinical Pharmacology
Georgia Ragia, Vangelis G Manolopoulos

Abstract

The COVID-19 pandemic caused by infection with the novel coronavirus SARS-CoV-2 is urging the scientific community worldwide to intense efforts for identifying and developing effective drugs and pharmacologic strategies to treat the disease. Many of the drugs that are currently in (pre)clinical development are addressing late symptoms of the disease. This review focuses on potential pharmacologic intervention at an early stage of infection which could result in less-infected individuals and less cases with severe COVID-19 disease due to reduced virus entry into the cells. We scanned the literature for evidence on drugs that target the virus entry machinery into host cells and consist mainly of ACE2 and TMPRSS2, as well as other cellular molecules regulating ACE2 expression, such as ADAM-17 and calmodulin. Several drugs/drug classes have been identified. Most of them are already used clinically for other indications. They include recombinant soluble ACE2, indirect ACE2 modulators (angiotensin receptor blockers, calmodulin antagonists, selective oestrogen receptor modifiers), TMPRSS2 inhibitors (camostat mesylate, nafamostat mesylate, antiandrogens, inhaled corticosteroids) and ADAM-17 enhancers (5-fluorouracil). Several agents h...Continue Reading

References

Jan 13, 1984·Biochemical and Biophysical Research Communications·H Y Lam
Aug 10, 2004·Journal of Pineal Research·Elena Soto-VegaGloria Benitez-King
Mar 26, 2005·The EMBO Journal·Wenhui LiMichael Farzan
May 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Heike HofmannStefan Pöhlmann
Jun 7, 2008·American Journal of Hypertension·Theodore W Kurtz, Michal Pravenec
Feb 27, 2010·Critical Reviews in Biochemistry and Molecular Biology·Monika Gooz
Jun 24, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Joan N KyulaPatrick G Johnston
Oct 11, 2013·Molecular Endocrinology·Liesbeth ClinckemalieFrank Claessens
May 21, 2014·Antimicrobial Agents and Chemotherapy·Julie DyallMatthew B Frieman
Feb 11, 2015·Antiviral Research·Yanchen ZhouGraham Simmons
Nov 3, 2016·Frontiers in Physiology·Jiaxi XuMaria S França-Silva
Sep 8, 2017·Critical Care : the Official Journal of the Critical Care Forum·Akram KhanAili L Lazaar
Dec 20, 2018·MBio·Marhiah C Montoya, Damian J Krysan
Mar 21, 2020·Cell Discovery·Yadi ZhouFeixiong Cheng
Mar 29, 2020·Life Sciences·Rui ZhangRussel J Reiter
Apr 14, 2020·JAMA : the Journal of the American Medical Association·James M SandersJames B Cutrell
Apr 22, 2020·Antimicrobial Agents and Chemotherapy·Markus HoffmannStefan Pöhlmann
Apr 24, 2020·Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Société Canadienne Des Sciences Pharmaceutiques·Zsuzsanna Suba
Apr 30, 2020·American Journal of Respiratory and Critical Care Medicine·Michael C PetersJohn V Fahy
May 2, 2020·The New England Journal of Medicine·Mandeep R MehraAmit N Patel
May 2, 2020·The New England Journal of Medicine·Giuseppe ManciaGiovanni Corrao
May 2, 2020·The New England Journal of Medicine·Harmony R ReynoldsJudith S Hochman
May 11, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M MontopoliA Alimonti
May 26, 2020·The Journal of Allergy and Clinical Immunology·Peter BraddingSalman Siddiqui
Mar 17, 2021·Cell Discovery·Yadi ZhouFeixiong Cheng

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Citations

Sep 3, 2020·Journal of Clinical Pathology·Michelle Thunders, Brett Delahunt
Dec 11, 2020·International Immunopharmacology·Joshua Adedeji BolarinAdenike Bernice-Eloise Adeoye
Jan 12, 2021·Reviews in Medical Virology·Mohammad Mahmudur RahmanAsif Ahmed
Jan 7, 2021·International Journal of Environmental Research and Public Health·Jing QiShuilin Jin
Jan 21, 2021·International Journal of Molecular Sciences·Anna StasiłowiczJudyta Cielecka-Piontek
Feb 3, 2021·The Journal of Microbiology·Subin HongWonsik Lee
Mar 7, 2021·Cytokine & Growth Factor Reviews·Narayanappa AmrutaGregory Bix
Apr 20, 2021·Structural Chemistry·Joyanta Kumar Saha, Md Jahir Raihan
May 9, 2021·Scientific Reports·Alberto BartoloméUtpal B Pajvani
Jun 1, 2021·Immunopharmacology and Immunotoxicology·Payam Hashemi, Shaghayegh Pezeshki
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sajad FakhriJavier Echeverría
Jun 3, 2021·Journal of Clinical Medicine·Giuseppe CarotaGiovanni Li Volti
Jul 15, 2021·BioMed Research International·Arun Bahadur GurungKhalid Mashay Al-Anazi
Jun 2, 2021·JCI Insight·Farnaz FarshidfarHossein Ardehali
Jul 23, 2021·Bioscience Reports·Rajesh AhirwarSaroj Kumar
Aug 28, 2021·International Journal of Molecular Sciences·Young Soo KimJang-Gi Choi
Oct 15, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ramesh K PaidiKalipada Pahan

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Methods Mentioned

BETA
nuclear translocation

Clinical Trials Mentioned

NCT04335136
NCT04312009
NCT04353128
NCT04409522
NCT04321096
NCT04353284
NCT04418128
NCT04352400
NCT04446429
NCT04374279

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