Abstract
In response to the current pandemic caused by the novel SARS-CoV-2, identifying and validating effective therapeutic strategies is more than ever necessary. We evaluated the in vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum activities, together with drugs that are currently under evaluation in clinical trials for COVID-19 patients. We report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection, with estimated 50% inhibitory concentrations of 0.99, 5.2, 1.38, 3.5, 10.6 and 3 μM, respectively. Virus-directed plus host-directed drug combinations were also investigated. We report a strong antagonism between remdesivir and berberine, in contrast with remdesivir/diltiazem, for which we describe high levels of synergy, with mean Loewe synergy scores of 12 and peak values above 50. Combination of host-directed drugs with direct acting antivirals underscore further validation in more physiological models, yet they open up interesting avenues for the treatment of COVID-19.
References
Aug 25, 1972·Science·R W SidwellR K Robins
Dec 2, 2000·Nature Medicine·S CrottyC E Cameron
Mar 19, 2002·Antimicrobial Agents and Chemotherapy·Y FurutaK Shiraki
Feb 27, 2004·Thorax·C M ChuUNKNOWN HKU/UCH SARS Study Group
Jun 23, 2010·PloS One·Joseph PrescottBrian Hjelle
Jul 15, 2011·The Journal of General Virology·Adriaan H de WildeMartijn J van Hemert
Oct 3, 2013·Antiviral Research·Yousuke FurutaDale L Barnard
Apr 29, 2014·Antiviral Research·Julie BlaisingEve-Isabelle Pécheur
Sep 13, 2014·The Lancet Infectious Diseases·Jake DunningUNKNOWN International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)
Jan 12, 2016·Antiviral Research·Finny S VargheseTero Ahola
Aug 19, 2016·Journal of Virology·Finny S VargheseTero Ahola
Apr 6, 2017·Bioinformatics·Aleksandr IanevskiJing Tang
Jun 10, 2017·Pharmacology Research & Perspectives·Md Abdul Alim Al-Bari
Apr 13, 2018·Viruses·Jan HaviernikDaniel Ruzek
Oct 12, 2018·Phytotherapy Research : PTR·Yu-Qi YanZhen-You Jiang
Feb 15, 2019·Frontiers in Immunology·Andrés PizzornoManuel Rosa-Calatrava
Nov 28, 2019·The New England Journal of Medicine·Sabue MulanguUNKNOWN PALM Consortium Study Team
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Jan 28, 2020·Lancet·Chaolin HuangBin Cao
Feb 6, 2020·Cell Research·Manli WangGengfu Xiao
Mar 19, 2020·The New England Journal of Medicine·Bin CaoChen Wang
Mar 21, 2020·Lancet·Puja MehtaUNKNOWN HLH Across Speciality Collaboration, UK
Mar 23, 2020·The Lancet Infectious Diseases·Yang LiuWei Zhang
Apr 7, 2020·Antiviral Research·Ka-Tim ChoyHui-Ling Yen
Apr 23, 2020·BMJ : British Medical Journal·Shufa ZhengTingbo Liang
Citations
Aug 22, 2020·JAMA : the Journal of the American Medical Association·Christoph D SpinnerUNKNOWN GS-US-540-5774 Investigators
Oct 6, 2020·EMBO Molecular Medicine·Alexander SimonisJakob J Malin
Nov 26, 2020·Pathogens and Disease·Thekra KhushafaZhu Haixia
Dec 11, 2020·International Immunopharmacology·Camila B P da CostaHelena C Castro
Jan 20, 2021·Archives of Virology·Nima HemmatBehzad Baradaran
Jan 22, 2021·Expert Opinion on Therapeutic Patents·Ilaria VicentiFrancesco Saladini
Feb 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Isabella RomeoStefano Alcaro
Feb 18, 2021·PloS One·Matthew R Freidel, Roger S Armen
Nov 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mathieu GendrotBruno Pradines
Nov 13, 2020·EMBO Molecular Medicine·Vanessa MonteilAli Mirazimi
Feb 12, 2021·Biochemical and Biophysical Research Communications·Yasuteru SakuraiJiro Yasuda
Feb 16, 2021·Network Modeling and Analysis in Health Informatics and Bioinformatics·Sapan ShahGovind Lohiya
Dec 29, 2020·Expert Review of Clinical Immunology·Philippe GautretDidier Raoult
Dec 5, 2020·Biochemical and Biophysical Research Communications·Koichi Watashi
Mar 2, 2021·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Ravindra M MehtaHariprasad Kalpakam
Mar 7, 2021·Viruses·Finny S VargheseRonald P van Rij
Feb 23, 2021·International Journal of Quantum Chemistry·Syed Ajaz K KirmaniFaizul Azam
Mar 23, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhen-Zhen WangXiu-Min Li
Oct 21, 2020·EClinicalMedicine·Pablo Guisado-VascoDaniel Carnevali-Ruiz
Apr 6, 2021·IScience·Hirofumi OhashiTakaji Wakita
May 1, 2021·International Journal of Molecular Sciences·Gustavo José da Silva PereiraClaudia Bincoletto
May 6, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Olivier TerrierAnny Slama-Schwok
May 14, 2021·Nanomedicine·Richa VartakKetan Patel
May 18, 2021·Chemical Physics Letters·Eugene MamontovMatthew B Stone
Jun 11, 2021·Open Forum Infectious Diseases·Kyle LaurieChava Kimchi-Sarfaty
May 18, 2021·Virologica Sinica·Yun-Yun JinDeyin Guo
May 20, 2021·Antiviral Research·Jeremy R A PaullPhilippe A Gallay
May 31, 2021·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Yusuf Oloruntoyin AyipoMohd Nizam Mordi
Jun 11, 2021·Virology Journal·Kexin YanAndreas Suhrbier
Apr 28, 2021·Antimicrobial Agents and Chemotherapy·Santseharay RamirezJens Bukh
Aug 5, 2021·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Batu ÖzlüşenÖnder Ergönül
Aug 13, 2021·MMW Fortschritte der Medizin·Thomas Wittig
Aug 29, 2021·Pharmaceutics·Federico RomanoOscar Della Della Pasqua
Sep 7, 2021·Frontiers in Pharmacology·Hsing-Yu HsuShiow-Ju Lee
Oct 6, 2021·Nature Communications·Marion FerrenCyrille Mathieu
Nov 2, 2021·The Journal of Microbiology·Erica EspañoJeong-Ki Kim
Nov 11, 2021·Future Microbiology·Sarah AherfiDidier Raoult