Conv. Plasma
Nigella Sativa

All ivermectin studies
Meta analysis
study 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:   

Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity against SARS-CoV-2

Jitobaom et al., Research Square, doi:10.21203/
Oct 2021  
  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 102 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.
4,100+ studies for 60+ treatments.
In Vitro study showing a strong synergistic effect of ivermectin and favipiravir. Combining multiple antiviral drugs with different mechanisms of action helps to minimize drug resistance and toxicity.
For ivermectin alone, IC50 for Calu-3 was 0.2µM, supporting in vivo efficacy at 0.6 mg/kg.
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), 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, shows dose-dependent inhibition of wildtype and omicron variants Shahin, 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, inhibits SARS-CoV-2 3CLpro Mody, may inhibit SARS-CoV-2 RdRp activity Parvez (B), may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages Gao, 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.
Jitobaom et al., 14 Oct 2021, preprint, 8 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity against SARS-CoV-2
Kunlakanya Jitobaom, Chompunuch Boonarkart, Suwimon Manopwisedjaroen, Nuntaya Punyadee, Suparerk Borwornpinyo, Arunee Thitithanyanont, Panisadee Avirutnan, Prasert Auewarakul
Despite the urgent need for effective antivirals against SARS-CoV-2 to mitigate the catastrophic impact of the COVID-19 pandemic, there are still no proven effective and widely available antivirals for COVID-19 treatment. Favipiravir and Ivermectin are among common repurposed drugs, which have been provisionally used in some countries. There have been clinical trials with mixed results, and therefore, it is still inconclusive whether they are effective or should be dismissed. It is plausible that the lack of clearcut clinical bene ts was due to the nding of only marginal levels of in vivo antiviral activity. An obvious way to improve the activity of antivirals is to use them in synergistic combinations. Here we show that Favipiravir and Ivermectin had the synergistic effects against SARS-CoV-2 in Vero cells. The combination may provide better e cacy in COVID-19 treatment. In addition, we found that Favipiravir had an additive effect with Niclosamide, another repurposed anti-parasitic drug with anti-SARS-CoV-2 activity. However, the anti-SARS-CoV-2 activity of Favipiravir was drastically reduced when tested in Calu-3 cells. This suggested that this cell type might not be able to metabolize Favipiravir into its active form, and that this de ciency in some cell types may affect in vivo e cacy of this drug.
Vero E6 cells were seeded in 12-well plates at a density of 2.2×10 5 cells/well, which allowed 100% con uence to be reached within 18 hr. The culture medium was removed, and the cells were inoculated with 100µl of 10-fold serial dilutions of virus supernatants for 1 hr. at 37 o C with 5%CO 2 . After that, the virus supernatants were removed, and the cells were overlaid with 1.56% microcrystalline cellulose (Avicel, RC-591) in 2%FBS-MEM. The cells were further incubated in the standard condition for three days. The overlaid medium was removed, and the cells were xed with 10% (v/v) formalin in phosphatebuffered saline (PBS) for 2 hr. The xed infected cells were washed in tap water, stained with 1% (w/v) crystal violet in 20% (v/v) ethanol for 5 min and washed to remove the excess dyes. The plaques were counted, and the viral titers were calculated in plaque forming units per ml (pfu/ml). 50% cell culture infectious dose (TCID 50 ) endpoint dilution assay Vero E6 cells were seeded in 96-well plates at a density of 3×10 4 cells/well. The culture medium was removed, and the cells were incubated with half-log10 serial dilution of the virus stock for 48 hr. at 37 o C with 5%CO 2 . After that, the cells were xed with 1:1 methanol/acetone for 30 min at 4 o C and the infectivity was detected with an antibody against the SARS-CoV-2 nucleocapsid protein (40143-R001, Sino Biological). The viral TCID 50 titers were calculated using the Reed and Muench method 73 . One-step qRT-PCR for..
Aasld, HCV Guidance: Recommendations for testing, managing, and treating Hepatitis C Virus infection
Agrawal, Raju, Udwadia, Favipiravir: A new and emerging antiviral option in COVID-19
Alam, Therapeutic effectiveness and safety of repurposing drugs for the treatment of COVID-19: position standing in 2021, Front Pharmacol12, doi:10.3389/fphar.2021.659577
Ansems, Remdesivir for the treatment of COVID-19, Cochrane Database Syst Rev8, doi:10.1002/14651858.Cd014962
Backer, A randomized, double-blind, placebo-controlled phase 1 trial of inhaled and intranasal niclosamide: A broad spectrum antiviral candidate for treatment of COVID-19, Lancet Reg Health Eur4, doi:10.1016/j.lanepe.2021.100084
Baraka, Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus, Eur J Clin Pharmacol50, doi:10.1007/s002280050131
Baranovich, T-705 (favipiravir) induces lethal mutagenesis in in uenza A H1N1 viruses in vitro, J Virol87, doi:10.1128/jvi.02346-12
Bobrowski, Synergistic and antagonistic drug combinations against SARS-CoV-2, Mol Ther29, doi:10.1016/j.ymthe.2020.12.016
Bryant, Ivermectin for prevention and treatment of COVID-19 infection: a systematic review, meta-analysis, and trial sequential analysis to inform clinical guidelines, Am J Ther28, doi:10.1097/mjt.0000000000001402
Cai, Experimental treatment with favipiravir for COVID-19: an open-label control study, Engineering, doi:10.1016/j.eng.2020.03.007
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral, doi:10.1016/j.antiviral.2020.104787
Day, Siu, Approaches to modernize the combination drug development paradigm, Genome Med, doi:10.1186/s13073-016-0369-x
Delang, Abdelnabi, Neyts, Favipiravir as a potential countermeasure against neglected and emerging RNA viruses, Antiviral, doi:10.1016/j.antiviral.2018.03.003
Dittmar, Drug repurposing screens reveal cell-type-speci c entry pathways and FDA-approved drugs active against SARS-Cov-2, Cell, doi:10.1016/j.celrep.2021.108959
Driouich, Favipiravir antiviral e cacy against SARS-CoV-2 in a hamster model, Nat Commun12, doi:10.1038/s41467-021-21992-w
Escribano-Romero, Jiménez De Oya, Domingo, Saiz, Extinction of West Nile Virus by Favipiravir through Lethal Mutagenesis, Antimicrob Agents Chemother61, doi:10.1128/aac.01400-17
Fang, Identi cation of three antiviral inhibitors against Japanese encephalitis virus from library of pharmacologically active compounds 1280, PLoS One8, doi:10.1371/journal.pone.0078425
Favié, Pharmacokinetics of favipiravir during continuous venovenous haemo ltration in a critically ill patient with in uenza, Antivir Ther23, doi:10.3851/imp3210
Furuta, Komeno, Nakamura, Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase, Proc Jpn Acad Ser B Phys Biol Sci93, doi:10.2183/pjab.93.027
Furuta, T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections, Antiviral Res82, doi:10.1016/j.antiviral.2009.02.198
Furuta, T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections, Antiviral Res82, doi:10.1016/j.antiviral.2009.02.198
Ganguly, SYBR green one-step qRT-PCR for the detection of SARS-CoV-2 RNA in saliva, doi:10.1101/2020.05.29.109702%JbioRxiv
Gassen, SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection, Nat Commun10, doi:10.1038/s41467-019-13659-4
Goldhill, Favipiravir-resistant in uenza A virus shows potential for transmission, PLoS, doi:10.1371/journal.ppat.1008937
Guedj, Antiviral e cacy of favipiravir against Ebola virus: A translational study in cynomolgus macaques, PLoS, doi:10.1371/journal.pmed.1002535
Guzzo, Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects, J Clin Pharmacol42, doi:10.1177/009127002401382731
Götz, In uenza A viruses escape from MxA restriction at the expense of e cient nuclear vRNP import, Sci, doi:10.1038/srep23138
Hassanipour, The e cacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials, Sci, doi:10.1038/s41598-021-90551-6
Hassanipour, The e cacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials, Sci, doi:10.1038/s41598-021-90551-6
Hoffmann, Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2, Nature585, doi:10.1038/s41586-020-2575-3
Hoffmann, SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor, doi:10.1016/j.cell.2020.02.052
Huang, Yang, Yuan, Li, Kuang, Niclosamide inhibits lytic replication of Epstein-Barr virus by disrupting mTOR activation, Antiviral, doi:10.1016/j.antiviral.2016.12.002
Huchting, Vanderlinden, Van Berwaer, Meier, Naesens, Cell line-dependent activation and antiviral activity of T-1105, the non-uorinated analogue of T-705 (favipiravir), Antiviral, doi:10.1016/j.antiviral.2019.04.002
Hurt, Wheatley, Neutralizing Antibody Therapeutics for COVID-19, Viruses13
Ianevski, Giri, Aittokallio, SynergyFinder 2.0: visual analytics of multi-drug combination synergies, Nucleic Acids Research, doi:10.1093/nar/gkaa216%J
Irie, Pharmacokinetics of Favipiravir in Critically Ill Patients With COVID-19, Clin Transl, doi:10.1111/cts.12827
Jeffreys, Remdesivir-Ivermectin combination displays synergistic interaction with improved in vitro antiviral activity against SARS-CoV-2, BioRxiv, doi:10.1101/2020.12.23.424232%JbioRxiv
Jeon, Identi cation of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs, Antimicrob Agents Chemother64, doi:10.1128/aac.00819-20
Jochmans, Antiviral activity of Favipiravir (T-705) against a broad range of paramyxoviruses in vitro and against Human Metapneumovirus in hamsters, Antimicrob Agents Chemother60, doi:10.1128/aac.00709-16
Kadri, Lambourne, Mehellou, Niclosamide, a drug with many Repurposes, Chem Med, doi:10.1002/cmdc.201800100
Kamat, Kumari, Repurposing chloroquine against multiple diseases with special attention to SARS-CoV-2 and associated toxicity, Front Pharmacol12, doi:10.3389/fphar.2021.576093
Kanjanasirirat, High-content screening of Thai medicinal plants reveals Boesenbergia rotunda extract and its component Panduratin A as anti-SARS-CoV-2 agents, Sci, doi:10.1038/s41598-020-77003-3
Kao, The antiparasitic drug niclosamide inhibits dengue virus infection by interfering with endosomal acidi cation independent of mTOR, PLOS Negl Trop, doi:10.1371/journal.pntd.0006715
Kaptein, Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity, Proc Natl Acad Sci U S, doi:10.1073/pnas.2014441117
Kashour, E cacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis, J Antimicrob Chemother76, doi:10.1093/jac/dkaa403
Kim, Seong, Kumar, Shin, Favipiravir and Ribavirin Inhibit Replication of Asian and African Strains of Zika Virus in Different Cell Models, Viruses10, doi:10.3390/v10020072
Kongmanas, Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy, PLOS Negl Trop, doi:10.1371/journal.pntd.0008835
Li, Multi-targeted therapy of cancer by niclosamide: A new application for an old drug, Cancer, doi:10.1016/j.canlet.2014.04.003
Mazzon, Identi cation of broad-spectrum antiviral compounds by targeting viral entry, Viruses11, doi:10.3390/v11020176
Melville, Rodriguez, Dobrovolny, Investigating different mechanisms of action in combination therapy for in uenza, Front Pharmacol9, doi:10.3389/fphar.2018.01207
Mentré, Dose regimen of favipiravir for Ebola virus disease, Lancet Infect Dis15, doi:10.1016/S1473-3099(14)71047-3
Musa, Potential antiviral effect of chloroquine therapy against SARS-CoV-2 infection, Open Access Maced J Med Sci8, doi:10.3889/oamjms.2020.4854
Ngo, The time to offer treatments for COVID-19, Expert Opin Investig, doi:10.1080/13543784.2021.1901883
Nguyen, Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI trial reveals concentrations lower than targeted, PLoS Negl Trop, doi:10.1371/journal.pntd.0005389
Niyomdecha, Suptawiwat, Boonarkart, Jitobaom, Auewarakul, Inhibition of human immunode ciency virus type 1 by niclosamide through mTORC1 inhibition, Heliyon6, doi:10.1016/j.heliyon.2020.e04050
Ohashi, Potential anti-COVID-19 agents, cepharanthine and nel navir, and their usage for combination treatment, iScience24, doi:10.1016/j.isci.2021.102367
Phougat, Combination therapy: the propitious rationale for drug development, Comb Chem High Throughput Screen17, doi:10.2174/13862073113166660065
Pires De Mello, Clinical regimens of Favipiravir inhibit Zika virus replication in the hollowber infection model, Antimicrob Agents Chemother62, doi:10.1128/aac.00967-18
Popp, Metzendorf, Gould, Kranke, Meybohm et al., Ivermectin for preventing and treating COVID-19, Cochrane Database Syst Rev, doi:10.1002/14651858.CD015017.pub2
Reed, Muench, A simple method of estimating fty percent enpoint, Am J Epidemiol27, doi:10.1093/oxfordjournals.aje.a118408%J
Schilling, The WHO guideline on drugs to prevent COVID-19: small numbers-big conclusions, Wellcome Open Res6, doi:10.12688/wellcomeopenres.16741.1
Shannon, Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis, Nat Commun11, doi:10.1038/s41467-020-18463-z
Suputtamongkol, Ivermectin accelerates circulating nonstructural protein 1 (NS1) clearance in adult dengue patients: a combined phase 2/3 randomized double-blinded placebo controlled trial, Clin Infect, doi:10.1093/cid/ciaa1332
Tan, Tan, Chu, Chow, Combination treatment with Remdesivir and Ivermectin exerts highly synergistic and potent antiviral activity against murine coronavirus infection, Front Cell Infect Microbiol11, doi:10.3389/fcimb.2021.700502
Vallejos, Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19): a structured summary of a study protocol for a randomized controlled trial, Trials21, doi:10.1186/s13063-020-04813-1
Vincent, Chloroquine is a potent inhibitor of SARS coronavirus infection and spread, Virol J2, doi:10.1186/1743-422X-2-69
Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a speci c inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem, doi:10.1042/bj20120150
Wang, Quality of and recommendations for relevant clinical practice guidelines for COVID-19 management: a systematic review and critical appraisal, Front Med8, doi:10.3389/fmed.2021.630765
Wang, The mechanism of action of T-705 as a unique delayed chain terminator on in uenza viral polymerase transcription, Biophys, doi:10.1016/j.bpc.2021.106652
Who, -line antiretroviral regimens and postexposure prophylaxis and recommendations on early infant diagnosis of HIV
Xu, Antivirus effectiveness of ivermectin on dengue virus type 2 in Aedes albopictus, PLOS Negl Trop Dis12, doi:10.1371/journal.pntd.0006934
Xu, Shi, Li, Zhou, Broad spectrum antiviral agent Niclosamide and its therapeutic potential, ACS Infect Dis6, doi:10.1021/acsinfecdis.0c00052
Yadav, Wennerberg, Aittokallio, Tang, Searching for drug synergy in complex doseresponse landscapes using an interaction potency model, Comput Struct Biotechnol13, doi:10.1016/j.csbj.2015.09.001
Yang, The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer, Antiviral, doi:10.1016/j.antiviral.2020.104760
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