Analgesics
Antiandrogens
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Abstract
All ivermectin studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19ivm.org COVID-19 treatment researchIvermectinIvermectin (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

Mody et al., Communications Biology, doi:10.1038/s42003-020-01577-x
Jan 2021  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now known with p < 0.00000000001 from 101 studies, recognized in 22 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,900+ studies for 60+ treatments. c19ivm.org
Computational molecular modeling screening and in vitro analysis for inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme, showing that ivermectin blocked more than 85% of 3CLpro activity of SARS-CoV-2. Antiviral activity of ivermectin mediated through the blocking of α/β1 importin has been previously established, this analysis suggests an additional antiviral mechanism of ivermectin for SARS-CoV-2 via inhibitory effects on 3CLpro.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Jitobaom, Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Jitobaom, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), inhibits SARS-CoV-2 3CLpro Mody, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing Fauquet, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, Scheim, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 via IMPase inhibition Jitobaom, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, may inhibit SARS-CoV-2 RdRp activity Parvez (B), may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation Liu (C), shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), increases Bifidobacteria which play a key role in the immune system Hazan, has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.
Mody et al., 20 Jan 2021, peer-reviewed, 9 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents
Vicky Mody, Joanna Ho, Savannah Wills, Ahmed Mawri, Latasha Lawson, Maximilian C C J C Ebert, Guillaume M Fortin, Srujana Rayalam, Shashidharamurthy Taval
Communications Biology, doi:10.1038/s42003-020-01577-x
Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets.
Supplementary Data 1 provides the data set for Figs. 2-5 , and Supplementary Figure 2 and 3 . Supplementary Data 2 and 3 provides data set for 3CLpro-OTDs docking study and Supplementary Data 4 for PIs and VNIs (S score for Table 1 and structural analysis for Fig. 6 ). Supplementary Data 5 provides data set for MD simulation study of 3CLPro homodimer with ivermectin, Supplementary Data 6 for 3CLPro monomer with ivermectin and Supplementary Data 7 for 3CLPro monomer with micafungin (Fig. 7 ). Supplementary Data 5-7 provides data set for Supplementary Fig. 3 (S score comparison from MD simulation study). Any remaining information can be obtained from the corresponding author upon reasonable request. Author contributions V.M. and S.T. designed, performed and wrote the manuscript, S.R. performed the experiment and proofread the manuscript. M.E. performed MD simulation studies. G.M.F. helped with molecular docking studies. J.H., S.W., A.M., and L.L. collected the data on drugs. All authors reviewed the manuscript. Competing interests The authors declare no competing interests. Additional information Supplementary information is available for this paper at https://doi.org/10.1038/s42003-020-01577-x. Correspondence and requests for materials should be addressed to S.T. Reprints and permission information is available at http://www.nature.com/reprints Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and..
References
Anand, Ziebuhr, Wadhwani, Mesters, Hilgenfeld, Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs, Science
Astuti, Ysrafil, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): an overview of viral structure and host response, Diabetes Metab. Syndr
Baig, Computer aided drug design: success and limitations, Curr. Pharm. Des
Caly, Druce, Catton, Jans, Wagstaff, The FDAapproved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antivir. Res
Cao, A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19, N. Engl. J. Med
Gentile, Buonomo, Borgia, Ombitasvir: a potent pan-genotypic inhibitor of NS5A for the treatment of hepatitis C virus infection, Expert Rev. Anti Infect. Ther
Gorbalenya, Snijder, Viral cysteine proteinases, Perspect. Drug Discov. Des
Grein, Compassionate use of remdesivir for patients with severe Covid-19, N. Engl. J. Med
Heidary, Gharebaghi, Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen, J Antibiot
Holshue, First case of 2019 novel coronavirus in the United States, N. Engl. J. Med
Kneller, Structural plasticity of SARS-CoV-2 3CL Mpro active site cavity revealed by room temperature X-ray crystallography, Nat. Commun
Kosyna, Nagel, Kluxen, Kraushaar, Depping, The importin α/β-specific inhibitor Ivermectin affects HIF-dependent hypoxia response pathways, Biol. Chem
Li, De Clercq, Therapeutic options for the 2019 novel coronavirus (2019-nCoV), Nat. Rev. Drug Discov
Ma, Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease, Cell Res
Malvezzi, Uncovering false positives on a virtual screening search for cruzain inhibitors, Bioorg. Med. Chem. Lett
Moradpour, Penin, Hepatitis C virus proteins: from structure to function, Curr. Top. Microbiol. Immunol
Needle, Lountos, Waugh, Structures of the Middle East respiratory syndrome coronavirus 3C-like protease reveal insights into substrate specificity, Acta Crystallogr. D Biol. Crystallogr
Ou-Yang, Computational drug discovery, Acta Pharmacol. Sin
Perlin, Mechanisms of echinocandin antifungal drug resistance, Ann. N. Y Acad. Sci
Phillips, Scalable molecular dynamics on CPU and GPU architectures with NAMD, J. Chem. Phys
Rosa, Santos, Clinical trials on drug repositioning for COVID-19 treatment, Rev. Panam. Salud Publica
Sawicki, Sawicki, Coronavirus transcription: subgenomic mouse hepatitis virus replicative intermediates function in RNA synthesis, J. Virol
Sawicki, Sawicki, Coronaviruses use discontinuous extension for synthesis of subgenome-length negative strands, Adv. Exp. Med. Biol
Sethna, Hofmann, Brian, Minus-strand copies of replicating coronavirus mRNAs contain antileaders, J. Virol
Sethna, Hung, Brian, Coronavirus subgenomic minusstrand RNAs and the potential for mRNA replicons, Proc. Natl Acad. Sci
Smith, Jeremy, 2 viral spike protein and viral spike protein-human ACE2 interface, doi:10.26434/chemrxiv.11871402.v4
Strømgaard, Krogsgaard-Larsen, Madsen, Textbook of Drug Design and Discovery
Talluri, Computational protein design of bacteriocins based on structural scaffold of aureocin A53, Int. J. Bioinform. Res. Appl
Talluri, Virtual screening based prediction of potential drugs for COVID-19, Pharmacol. Toxicol, doi:10.20944/preprints202002.0418.v2
Ul Qamar, Alqahtani, Alamri, Chen, Structural basis of SARS-CoV-2 3CL(pro) and anti-COVID-19 drug discovery from medicinal plants, J. Pharm. Anal, doi:10.1016/j.jpha.2020.03.009
Van Der Watt, Targeting the nuclear import receptor Kpnβ1 as an anticancer therapeutic, Mol. Cancer Ther
Wagstaff, Rawlinson, Hearps, Jans, An AlphaScreen®-based assay for high-throughput screening for specific inhibitors of nuclear import, J. Biomol. Screen
Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem. J
Wan, Shang, Graham, Baric, Li, Receptor recognition by the novel coronavirus from wuhan: an analysis based on decade-long structural studies of SARS coronavirus, J. Virol, doi:10.1128/JVI.00127-20
Wu, A new coronavirus associated with human respiratory disease in China, Nature
Zhang, Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved alpha-ketoamide inhibitors, Science
Zhu, A novel coronavirus from patients with pneumonia in China, 2019, New Engl. J. Med
Zumla, Chan, Azhar, Hui, Yuen, Coronavirusesdrug discovery and therapeutic options, Nat. Rev. Drug Discov
Loading..
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.
  or use drag and drop   
Submit