All Studies Meta Analysis Recent:

Biophysical Analysis of Potential Inhibitors of SARS-CoV-2 Cell Recognition and Their Effect on Viral Dynamics in Different Cell Types: A Computational Prediction from In Vitro Experimental Data

González-Paz et al., ACS Omega, doi:10.1021/acsomega.3c06968

Feb 2024

Post
Facebook

Source PDF All Studies Meta AnalysisMeta

HCQ for COVID-19

1st treatment shown to reduce risk in March 2020

^*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.

Lower risk for mortality, hospitalization, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,100+ studies for 60+ treatments. c19hcq.org

In Silico study showing that nafamostat, camostat, chloroquine, hydroxychloroquine, telmisartan, and captopril may be beneficial for COVID-19 by inhibiting SARS-CoV-2 cell entry and replication in multiple cell types expressing ACE2 and TMPRSS2 receptors. Authors used mathematical models to predict the susceptibility of different cell lines to SARS-CoV-2 infection based on their expression of various viral entry receptors. The CaLu3 cell line was predicted to be most susceptible, potentially due to high expression of CD147 and Cathepsin-L. Molecular docking simulations found that nafamostat and camostat had the most favorable binding affinities and stability when interacting with the SARS-CoV-2 spike protein receptor-binding domain (RBD) compared to other tested compounds. Chloroquine and hydroxychloroquine were predicted to have around 80% and 72% antiviral efficacy, respectively, possibly by blocking the interaction between the spike protein and ACE2 receptor. Telmisartan and captopril, both related to the renin-angiotensin system, were predicted to have 56-59% antiviral efficacy, potentially by reducing ACE2 expression and making cells less susceptible to infection. The study predicts that these compounds could significantly reduce viral infectivity and replication in Vero E6, HEK293, HeLa, and CaLu3 cells, with nafamostat being the most effective overall.

31 preclinical studies support the efficacy of HCQ for COVID-19:

8 In Silico studies Alkafaas, Baildya, González-Paz, Hussein, Navya, Noureddine, Tarek, Yadav

2 In Vivo animal studies Shu-Han Lin, Wen

Important missing comments or errors? Let us know.

1. Alkafaas et al., A study on the effect of natural products against the transmission of B.1.1.529 Omicron, Virology Journal, doi:10.1186/s12985-023-02160-6.biomedcentral.com, doi.org.

2. Alsmadi et al., The In Vitro, In Vivo, and PBPK Evaluation of a Novel Lung-Targeted Cardiac-Safe Hydroxychloroquine Inhalation Aerogel, AAPS PharmSciTech, doi:10.1208/s12249-023-02627-3.springer.com, doi.org.

3. Andreani et al., In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228.sciencedirect.com, doi.org.

4. Baildya et al., Inhibitory capacity of Chloroquine against SARS-COV-2 by effective binding with Angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies, Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891.sciencedirect.com, doi.org.

5. Clementi et al., Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro, Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704.frontiersin.org, doi.org.

6. Dang et al., Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein, bioRxiv, doi:10.1101/2021.03.16.435741.biorxiv.org, doi.org.

7. Delandre et al., Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants, Pharmaceuticals, doi:10.3390/ph15040445.mdpi.com, doi.org.

8. Faísca et al., Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2, Pharmaceutics, doi:10.3390/pharmaceutics14040877.mdpi.com, doi.org.

9. González-Paz et al., Biophysical Analysis of Potential Inhibitors of SARS-CoV-2 Cell Recognition and Their Effect on Viral Dynamics in Different Cell Types: A Computational Prediction from In Vitro Experimental Data, ACS Omega, doi:10.1021/acsomega.3c06968.acs.org, doi.org.

10. Hussein et al., Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19, Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979.sciencedirect.com, doi.org.

11. Kamga Kapchoup et al., In vitro effect of hydroxychloroquine on pluripotent stem cells and their cardiomyocytes derivatives, Frontiers in Pharmacology, doi:10.3389/fphar.2023.1128382.frontiersin.org, doi.org.

12. Liu et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0.nature.com, doi.org.

13. Miao et al., SIM imaging resolves endocytosis of SARS-CoV-2 spike RBD in living cells, Cell Chemical Biology, doi:10.1016/j.chembiol.2023.02.001.sciencedirect.com, doi.org.

14. Milan Bonotto et al., Cathepsin inhibitors nitroxoline and its derivatives inhibit SARS-CoV-2 infection, Antiviral Research, doi:10.1016/j.antiviral.2023.105655.sciencedirect.com, doi.org.

15. Mohd Abd Razak et al., In Vitro Anti-SARS-CoV-2 Activities of Curcumin and Selected Phenolic Compounds, Natural Product Communications, doi:10.1177/1934578X231188861.sagepub.com, doi.org.

16. Navya et al., A computational study on hydroxychloroquine binding to target proteins related to SARS-COV-2 infection, Informatics in Medicine Unlocked, doi:10.1016/j.imu.2021.100714.sciencedirect.com, doi.org.

17. Noureddine et al., Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations, Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334.sciencedirect.com, doi.org.

18. Ou et al., Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2, PLOS Pathogens, doi:10.1371/journal.ppat.1009212.plos.org, doi.org.

19. Purwati et al., An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia, PLOS One, doi:10.1371/journal.pone.0252302.plos.org, doi.org.

20. Shang et al., Inhibitors of endosomal acidification suppress SARS-CoV-2 replication and relieve viral pneumonia in hACE2 transgenic mice, Virology Journal, doi:10.1186/s12985-021-01515-1.biomedcentral.com, doi.org.

21. Sheaff, R., A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity, bioRxiv, doi:10.1101/2020.08.02.232892.biorxiv.org, doi.org.

22. Shu-Han Lin et al., Inhalable Chitosan-Based Hydrogel as a Mucosal Adjuvant for Hydroxychloroquine in the Treatment for SARS-CoV-2 Infection in a Hamster Model, Journal of Microbiology, Immunology and Infection, doi:10.1016/j.jmii.2023.08.001.sciencedirect.com, doi.org.

23. Tarek et al., Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention, European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6.springer.com, doi.org.

24. Wang et al., Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus, Phytomedicine, doi:10.1016/j.phymed.2020.153333.nih.gov, doi.org.

25. Wang (B) et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0.nature.com, doi.org.

26. Wen et al., Cholinergic α7 nAChR signaling suppresses SARS-CoV-2 infection and inflammation in lung epithelial cells, Journal of Molecular Cell Biology, doi:10.1093/jmcb/mjad048.oup.com, doi.org.

27. Yadav et al., Repurposing the Combination Drug of Favipiravir, Hydroxychloroquine and Oseltamivir as a Potential Inhibitor Against SARS-CoV-2: A Computational Study, Research Square, doi:10.21203/rs.3.rs-628277/v1.researchsquare.com, doi.org.

28. Yao et al., In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237.oup.com, doi.org.

29. Yuan et al., Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture, Communications Biology, doi:10.1038/s42003-022-03841-8.nature.com, doi.org.

González-Paz et al., 14 Feb 2024, peer-reviewed, 8 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

This Paper HCQ All

Biophysical Analysis of Potential Inhibitors of SARS-CoV-2 Cell Recognition and Their Effect on Viral Dynamics in Different Cell Types: A Computational Prediction from In Vitro Experimental Data

Lenin González-Paz, María Carla Lossada, María Laura Hurtado-León, Joan Vera-Villalobos, José L Paz, Yovani Marrero-Ponce, Felix Martinez-Rios, Ysaías. J Alvarado

ACS Omega, doi:10.1021/acsomega.3c06968

Recent reports have suggested that the susceptibility of cells to SARS-CoV-2 infection can be influenced by various proteins that potentially act as receptors for the virus. To investigate this further, we conducted simulations of viral dynamics using different cellular systems (Vero E6, HeLa, HEK293, and CaLu3) in the presence and absence of drugs (anthelmintic, ARBs, anticoagulant, serine protease inhibitor, antimalarials, and NSAID) that have been shown to impact cellular recognition by the spike protein based on experimental data. Our simulations revealed that the susceptibility of the simulated cell systems to SARS-CoV-2 infection was similar across all tested systems. Notably, CaLu3 cells exhibited the highest susceptibility to SARS-CoV-2 infection, potentially due to the presence of receptors other than ACE2, which may account for a significant portion of the observed susceptibility. Throughout the study, all tested compounds showed thermodynamically favorable and stable binding to the spike protein. Among the tested compounds, the anticoagulant nafamostat demonstrated the most favorable characteristics in terms of thermodynamics, kinetics, theoretical antiviral activity, and potential safety (toxicity) in relation to SARS-CoV-2 spike proteinmediated infections in the tested cell lines. This study provides mathematical and bioinformatic models that can aid in the identification of optimal cell lines for compound evaluation and detection, particularly in studies focused on repurposed drugs and their mechanisms of action. It is important to note that these observations should be experimentally validated, and this research is expected to inspire future quantitative experiments.

Notes The authors declare no competing financial interest. ■ ACKNOWLEDGMENTS This research was supported by regular funds of the Venezuelan Institute for Scientific Research (IVIC). J.L.P. thanks the Vicerrectorado de Investigación y Postgrado of the Universidad Nacional Mayor de San Marcos for the computational resources used.

References

Abernathy, Abernathy, Stevens, A mathematical model for tumor growth and treatment using virotherapy, AIMS Math, doi:10.3934/math.2020265

Appelberg, Gupta, Svensson Akusjärvi, Ambikan, Mikaeloff et al., Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells, Emerging microbes & infections, doi:10.1080/22221751.2020.1799723

Baccam, Beauchemin, Macken, Hayden, Perelson, Kinetics of influenza A virus infection in humans, Journal of virology, doi:10.1128/JVI.01623-05

Bairoch, The cellosaurus, a cell-line knowledge resource, Journal of biomolecular techniques: JBT, doi:10.7171/jbt.18-2902-002

Banerjee, Eckert, Schrey, Preissner, ProTox-II: a webserver for the prediction of toxicity of chemicals, Nucleic acids research, doi:10.1093/nar/gky318

Bar-On, Flamholz, Phillips, Milo, Science Forum: SARS-CoV-2 (COVID-19) by the numbers, Elife, doi:10.7554/eLife.57309

Bollavaram, Leeman, Lee, Kulkarni, Upshaw et al., Multiple sites on SARS-CoV-2 spike protein are susceptible to proteolysis by cathepsins B, Protein science: a publication of the Protein Society, doi:10.1002/pro.4073

Burlingham, Widlanski, An intuitive look at the relationship of Ki and IC50: a more general use for the Dixon plot, J. Chem. Educ, doi:10.1021/ed080p214?urlappend=%3Fref%3DPDF&jav=VoR&rel=cite-as

Campbell, Boilard, Rondina, Is there a role for the ACE2 receptor in SARS-CoV-2 interactions with platelets, Journal of Thrombosis and Haemostasis, doi:10.1111/jth.15156

Cer, Mudunuri, Stephens, Lebeda, IC50-to-Ki: a web-based tool for converting IC50 to Ki values for inhibitors of enzyme activity and ligand binding, Nucleic Acids Res, doi:10.1093/nar/gkp253

Chen, Liu, Guo, Emerging coronaviruses: Genome structure, replication, and pathogenesis, J. Med. Virol, doi:10.1002/jmv.25681

Choi, Son, Kim, Na, Uversky et al., Improved prediction of protein-protein interactions by a modified strategy using three conventional docking software in combination, Int. J. Biol. Macromol, doi:10.1016/j.ijbiomac.2023.126526

Chu, Chan, Yuen, Shuai, Yuan et al., Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study, Lancet. Microbe, doi:10.1016/S2666-5247(20)30004-5

Coghi, Yang, Ng, Haynes, Memo et al., A drug repurposing approach for antimalarials interfering with SARS-CoV-2 spike protein receptor binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2), Pharmaceuticals, doi:10.3390/ph14100954

Cuervo, Grandvaux, ACE2: Evidence of role as entry receptor for SARS-CoV-2 and implications in comorbidities, Elife, doi:10.7554/eLife.61390

Czuppon, Débarre, Goncalves, Tenaillon, Perelson et al., Success of prophylactic antiviral therapy for SARS-CoV-2: Predicted critical efficacies and impact of different drug-specific mechanisms of action, PLoS computational biology, doi:10.1371/journal.pcbi.1008752

De Bruin, Schneider, Reus, Talmon, Ciesek et al., Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection, Int. J. Mol. Sci, doi:10.3390/ijms23031049

Digre, Lindskog, The human protein atlas�spatial localization of the human proteome in health and disease, Protein Sci, doi:10.1002/pro.3987

Dittmar, Lee, Whig, Segrist, Li et al., Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2, Cell reports, doi:10.1016/j.celrep.2021.108959

Dobrindt, Hoagland, Seah, Kassim, O'shea et al., Common genetic variation in humans impacts in vitro susceptibility to SARS-CoV-2 infection, Stem Cell Rep, doi:10.1016/j.stemcr.2021.02.010

Duru, Umar, Duru, Enenebeaku, Ngozi-Olehi et al., Blocking the interactions between human ACE2 and coronavirus spike glycoprotein by selected drugs: a computational perspective, Environ. Anal. Health Toxicol, doi:10.5620/eaht.2021010?urlappend=%3Fref%3DPDF&jav=VoR&rel=cite-as

Felline, Seeber, Fanelli, webPSN v2. 0: a webserver to infer fingerprints of structural communication in biomacromolecules, Nucleic Acids Res, doi:10.1093/nar/gkaa397

Fenizia, Galbiati, Vanetti, Vago, Clerici et al., SARS-CoV-2 Entry: At the Crossroads of CD147 and ACE2, Cell, doi:10.3390/cells10061434

Fiege, Thiede, Nanda, Matchett, Moore et al., Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium, PLoS Pathogens, doi:10.1371/journal.ppat.1009292

Gendrot, Javelle, Clerc, Savini, Pradines, Chloroquine as a prophylactic agent against COVID-19?, International journal of antimicrobial agents, doi:10.1016/j.ijantimicag.2020.105980

Gesztelyi, Zsuga, Kemeny-Beke, Varga, Juhasz et al., The Hill equation and the origin of quantitative pharmacology, Archive for history of exact sciences, doi:10.1007/s00407-012-0098-5

Goncalves, Bertrand, Ke, Comets, De Lamballerie et al., Timing of antiviral treatment initiation is critical to reduce SARS-CoV-2 viral load, CPT: Pharmacometrics Syst. Pharmacol, doi:10.1002/psp4.12543

González-Paz, Alvarado, Hurtado-León, Lossada, Vera-Villalobos et al., Comparative study of SARS-CoV-2 infection in different cell types: Biophysical-computational approach to the role of potential receptors, Computers in biology and medicine, doi:10.1016/j.compbiomed.2022.105245

González-Paz, Lossada, Fernández-Materán, Paz, Vera-Villalobos et al., Can Non-steroidal Antiinflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study, Front. Phys, doi:10.3389/fphy.2020.587606

González-Paz, Lossada, Moncayo, Romero, Paz et al., A Bioinformatics Study of Structural Perturbation of 3CL-Protease and the HR2-Domain of SARS-CoV-2 Induced by Synergistic Interaction with Ivermectins, Biointerface Research in Applied. Chemistry, doi:10.33263/BRIAC112.98139826?urlappend=%3Fref%3DPDF&jav=VoR&rel=cite-as

Gupta, Biswal, Panda, Ray, Rana, Binding mechanism and structural insights into the identified protein target of COVID-19 and importin-α with in-vitro effective drug ivermectin, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1839564

Gutiérrez-Chamorro, Riveira-Munõz, Barrios, Palau, Nevot et al., SARS-CoV-2 Infection Modulates ACE2 Function and Subsequent Inflammatory Responses in Swabs and Plasma of COVID-19 Patients, Viruses, doi:10.3390/v13091715

Hempel, Raich, Olsson, Azouz, Klingler et al., Molecular mechanism of inhibiting the SARS-CoV-2 cell entry facilitator TMPRSS2 with camostat and nafamostat, Chemical Science, doi:10.1039/D0SC05064D

Hikmet, Méar, Edvinsson, Micke, Uhlén et al., The protein expression profile of ACE2 in human tissues, Molecular systems biology, doi:10.15252/msb.20209610

Hoffmann, Kleine-Weber, Schroeder, Kruger, Herrler et al., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell, doi:10.1016/j.cell.2020.02.052

Isaac-Lam, Molecular modeling of the interaction of ligands with ACE2-SARS-CoV-2 spike protein complex, silico pharmacology, doi:10.1007/s40203-021-00114-w

Jafary, Jafari, Ganjalikhany, In silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensinconverting enzyme 2, Sci. Rep, doi:10.1038/s41598-021-86380-2

Ji, Svensson, Zoufir, Bender, eMolTox: prediction of molecular toxicity with confidence, Bioinformatics, doi:10.1093/bioinformatics/bty135

Johnson, Xie, Bailey, Loss of FURIN cleavage site attenuates SARS-CoV-2 pathogenesis, Nature, doi:10.1038/s41586-021-03237-4

Kalhor, Sadeghi, Abolhasani, Kalhor, Rahimi, Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1824816

Kasahara, Terazawa, Itaya, Goto, Nakamura et al., myPresto/omegagene 2020: a molecular dynamics simulation engine for virtual-system coupled sampling, Biophysics and Physicobiology, doi:10.2142/biophysico.BSJ-2020013

Keyaerts, Vijgen, Maes, Neyts, Ranst, Growth kinetics of SARS-coronavirus in Vero E6 cells, Biochem. Biophys. Res. Commun, doi:10.1016/j.bbrc.2005.02.085

Kim, Melgoza, Jiang, Guo, The effect of reninangiotensin-aldosterone system inhibitors on organ-specific ace2 expression in zebrafish and its implications for COVID-19, Sci. Rep, doi:10.1038/s41598-021-03244-5

Kishimoto, Uemura, Sanaki, Sato, Hall et al., TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein, Viruses, doi:10.3390/v13030384

Kitagawa, Arai, Iida, Mukai, Furukawa et al., A phase I study of high dose camostat mesylate in healthy adults provides a rationale to repurpose the TMPRSS2 inhibitor for the treatment of COVID-19, Clinical and translational science, doi:10.1111/cts.13052

Kumar, Ter Ellen, Bouma, Troost, Van De Pol et al., Moxidectin and Ivermectin Inhibit SARS-CoV-2 Replication in Vero E6 Cells but Not in Human Primary Bronchial Epithelial Cells, Antimicrob. Agents Chemother, doi:10.1128/AAC.01543-21

Kumari, Kumar, Dhankhar, Dalal, Promising antivirals for PLpro of SARS-CoV-2 using virtual screening, molecular docking, dynamics, and MMPBSA, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2022.2071340

Kyrou, Randeva, Spandidos, Karteris, Not only ACE2�the quest for additional host cell mediators of SARS-CoV-2 infection: Neuropilin-1 (NRP1) as a novel SARS-CoV-2 host cell entry mediator implicated in COVID-19, Signal transduction and targeted therapy, doi:10.1038/s41392-020-00460-9

Li, Li, Huang, Wu, Liu et al., Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs, Proc. Natl. Acad. Sci. U. S. A, doi:10.1073/pnas.2010470117

Liu, Han, Blair, Kenst, Qin et al., SARS-CoV-2 Infects Endothelial Cells In Vivo and In Vitro, Frontiers in cellular and infection microbiology, doi:10.3389/fcimb.2021.701278

Liu, Wang, Zhou, Zhao, Zhang et al., Potential role of ACE2 in coronavirus disease 2019 (COVID-19) prevention and management, Journal of translational internal medicine, doi:10.2478/jtim-2020-0003

Matsuyama, Kawase, Nao, Shirato, Ujike et al., The Inhaled Steroid Ciclesonide Blocks SARS-CoV-2 RNA Replication by Targeting the Viral Replication-Transcription Complex in Cultured Cells, Journal of virology, doi:10.1128/JVI.01648-20

Modrof, Kerschbaum, Farcet, Niemeyer, Corman et al., SARS-CoV-2 and the safety margins of cellbased biological medicinal products, Biologicals, doi:10.1016/j.biologicals.2020.08.010

Moon, Hong, Bae, Treatment effect of nafamostat mesylate in patients with COVID-19 pneumonia: study protocol for a randomized controlled trial, Trials, doi:10.1186/s13063-021-05760-1

Mosquera-Yuqui, Lopez-Guerra, Moncayo-Palacio, Targeting the 3CLpro and RdRp of SARS-CoV-2 with phytochemicals from medicinal plants of the Andean Region: molecular docking and molecular dynamics simulations, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1835716

Murgolo, Therien, Howell, Klein, Koeplinger et al., SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development, PLoS pathogens, doi:10.1371/journal.ppat.1009225

Nguyen, Binder, Boianelli, Meyer-Hermann, Hernandez-Vargas, Ebola virus infection modeling and identifiability problems, Frontiers in microbiology, doi:10.3389/fmicb.2015.00257

Nguyen, Hernández-Vargas, Parameter Estimation in Mathematical Models of Viral Infections Using R, Methods in molecular biology, doi:10.1007/978-1-4939-8678-1_25

Owen, Neary, Box, Sharp, Tatham et al., Evaluation of intranasal nafamostat or camostat for SARS-CoV-2 chemoprophylaxis in Syrian golden hamsters, bioRxiv, doi:10.1101/2021.07.08.451654?urlappend=%3Fref%3DPDF&jav=VoR&rel=cite-as

Park, Kim, Park, Maharjan, Kim et al., Differential Signaling and Virus Production in Calu-3 Cells and Vero Cells upon SARS-CoV-2 Infection, Biomolecules & therapeutics, doi:10.4062/biomolther.2020.226

Peixoto, Monteiro, Rocha, Veiga-Fernandes, Quantification of multiple gene expression in individual cells, Genome research, doi:10.1101/gr.2890204

Perelson, Deeks, Drug effectiveness explained: the mathematics of antiviral agents for HIV, Science translational medicine, doi:10.1126/scitranslmed.3002656

Pontelli, Castro, Martins, Veras, Serra et al., Infection of human lymphomononuclear cells by SARS-CoV-2. bioRxiv: the preprint server for biology, doi:10.1101/2020.07.28.225912?urlappend=%3Fref%3DPDF&jav=VoR&rel=cite-as

Prinz, Hill coefficients, dose-response curves and allosteric mechanisms, Journal of chemical biology, doi:10.1007/s12154-009-0029-3

Quiroga, Villarreal, Vinardo, A scoring function based on autodock vina improves scoring, docking, and virtual screening, PloS one, doi:10.1371/journal.pone.0155183

Rajah, Hubert, Bishop, Saunders, Robinot et al., SARS-CoV-2 Alpha, Beta, and Delta variants display enhanced Spike-mediated syncytia formation, EMBO J, doi:10.15252/embj.2021108944

Reus, Schneider, Ulshöfer, Henke, Bojkova et al., Characterization of ACE Inhibitors and AT1R Antagonists with Regard to Their Effect on ACE2 Expression and Infection with SARS-CoV-2 Using a Caco-2 Cell Model, Life, doi:10.3390/life11080810

Rothlin, Vetulli, Duarte, Pelorosso, Telmisartan as tentative angiotensin receptor blocker therapeutic for COVID-19, Drug Dev. Res, doi:10.1002/ddr.21679

Saraswat, Riaz, Patel, In-silico study for the screening and preparation of ionic liquid-AVDs conjugate to combat COVID-19 surge, J. Mol. Liq, doi:10.1016/j.molliq.2022.119277

Saraswat, Singh, Patel, A computational approach for the screening of potential antiviral compounds against SARS-CoV-2 protease: Ionic liquid vs herbal and natural compounds, Journal of molecular liquids, doi:10.1016/j.molliq.2021.115298

Schroeder, Pott, Niemeyer, Veith, Richter et al., Interferon antagonism by SARS-CoV-2: a functional study using reverse genetics, Lancet Microbe, doi:10.1016/S2666-5247(21)00027-6

Shamsi, Mohammad, Anwar, Alajmi, Hussain et al., Glecaprevir and Maraviroc are high-affinity inhibitors of SARS-CoV-2 main protease: possible implication in COVID-19 therapy, Bioscience Reports, doi:10.1042/BSR20201256

Shilts, Crozier, Greenwood, Lehner, Wright, No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor, Sci. Rep, doi:10.1038/s41598-020-80464-1

Smart, Fawkes, Goggin, Pennick, Rainsford et al., A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-19), ACE2, and the immune system: a dichotomy of expectation and reality, Inflammopharmacology, doi:10.1007/s10787-020-00745-z

Sulaiman, Chung, Angel, Tsay, Wu et al., Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome, Nat. Microbiol, doi:10.1038/s41564-021-00961-5

Takayama, In vitro and animal models for SARS-CoV-2 research, Trends in pharmacological sciences, doi:10.1016/j.tips.2020.05.005

Ter Ellen, Dinesh Kumar, Bouma, Troost, Van De Pol et al., Resveratrol and Pterostilbene Inhibit SARS-CoV-2 Replication in Air-Liquid Interface Cultured Human Primary Bronchial Epithelial Cells, Viruses, doi:10.3390/v13071335

Terrier, Dilly, Pizzorno, Chalupska, Humpolickova et al., Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus, Molecules, doi:10.3390/molecules26092593

Tiwari, Fuglebakk, Hollup, Skjaerven, Cragnolini et al., WEBnm@ v2.0: Web server and services for comparing protein flexibility, BMC Bioinformatics, doi:10.1186/s12859-014-0427-6

Vincent, Bergeron, Benjannet, Erickson, Rollin et al., Chloroquine is a potent inhibitor of SARS coronavirus infection and spread, Virology journal, doi:10.1186/1743-422X-2-69

Viveiros, Gheblawi, Aujla, Sosnowski, Seubert et al., Sex-and age-specific regulation of ACE2: Insights into severe COVID-19 susceptibility, Journal of molecular and cellular cardiology, doi:10.1016/j.yjmcc.2021.11.003

Wang, Qiu, Hou, Deng, Xu et al., AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells, Cell Res, doi:10.1038/s41422-020-00460-y

Wang, Wang, Li, Lei, Wang et al., farPPI: a webserver for accurate prediction of proteinligand binding structures for small-molecule PPI inhibitors by MM/ PB(GB)SA methods, Bioinformatics, doi:10.1093/bioinformatics/bty879

Whittaker, SARS-CoV-2 spike and its adaptable FURIN cleavage site, Lancet Microbe, doi:10.1016/S2666-5247(21)00174-9

Wysocki, Lores, Ye, Soler, Batlle, Kidney and lung ACE2 expression after an ACE inhibitor or an Ang II receptor blocker: implications for COVID-19, Journal of the American Society of Nephrology, doi:10.1681/ASN.2020050667

Xie, Ying, Xie, Smpbs, Web server for computing biomolecular electrostatics using finite element solvers of size modified Poisson-Boltzmann equation, J. Comput. Chem, doi:10.1002/jcc.24703

Xiu, Dick, Ju, Mirzaie, Abdi et al., Inhibitors of SARS-CoV-2 entry: current and future opportunities, Journal of medicinal chemistry, doi:10.1021/acs.jmedchem.0c00502?urlappend=%3Fref%3DPDF&jav=VoR&rel=cite-as

Yamamoto, Matsuyama, Li, Takeda, Kawaguchi et al., Identification of nafamostat as a potent inhibitor of Middle East respiratory syndrome coronavirus S proteinmediated membrane fusion using the split-protein-based cell-cell fusion assay, Antimicrob. Agents Chemother, doi:10.1128/AAC.01043-16

Yu, Organoids: a new model for SARS-CoV-2 translational research, International. Journal of Stem Cells, doi:10.15283/ijsc20169

Zhang, Chu, Han, Shuai, Deng et al., SARS-CoV-2 infects human neural progenitor cells and brain organoids, Cell research, doi:10.1038/s41422-020-0390-x

Zhuravel, Khmelnitskiy, Burlaka, Gritsan, Goloshchekin et al., Nafamostat in hospitalized patients with moderate to severe COVID-19 pneumonia: a randomised Phase II clinical trial, EClinicalMedicine, doi:10.1016/j.eclinm.2021.101169

Download Image

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0