investigational treatment of COVID-19
Jump to navigation
Jump to search
Clinical trials
- Paxlovid (PF-07321332/ritonavir) oral, outpatient, from Pfizer[10]
- emergency use authorization from the FDA December 2021
- molnupiravir oral, outpatient from Merk[8]
- ensitrelvir phase II/III randomized trial in Japan
- favipiravir (Avigan)[8]
- 4'-fluorouridine is an investigational drug that treats SARS-CoV2 in ferrets & respiratory syncytial virus (RSV) in mice[15]
- probenecid inhibits replication of SARS-CoV2 in animal models & human lung cells[16]
- nitazoxanide (Alinia) an antiprotozoal agent[8]
- niclosamide (Niclocide) an antihelmintic[8]
- opaganib (Yeliva) phase 2/3 for hospitalized patients
- reduces need for oxygen therapy
- JAK2/IRAK1 inhibitor pacritinib no better than placebo for treatment of patients with severe Covid-19[18]
- upamostat (RHB-107) phase 2/3 for outpatients
- serine protease inhibitor
- targets human cell factors involved in viral entry
- expected to be effective against emerging variants
- synthetic nanobody sequences can disrupt interaction between the spike glycoprotein & ACE2
- a trivalent nanobody, mNb6-tri, with femtomolar affinity for spike glycoprotein & picomolar neutralization of SARS-CoV2 infection retains function after aerosolization, lyophilization, & heat treatment which enables aerosol-mediated delivery directly to the airway epithelia[2]
- KB109 (a synthetic glycan microbiome metabolic therapy & oral agent)
- reduces hospitalizations & emergency room visits by 51% in 350 patients, & by 62% among patients with one or more co-morbidities in an early trial[3]
- compounds preventing SARS-CoV2 from replicating in at least one human cell line with favorable characteristics & already FDA-approved for other indications[4]
- ursodiol downregulates ACE2 (receptor for SARS Cov2) by binding to & inhibiting FXR which upregulates ACE2, thus may be useful for post-exposure prophyaxis of Covid-19, provided 1/2life of ACE2 is short, the effect of FXR on ACE2 is strong & the dose-response of ursodiol on FXR is favorable[19]
- fluvoxamine (SSRI & S1R agonist)
- may reduce risk of clinical deterioration in outpatients with COVID-19[5]
- not enough evidence to recommend for or against use of fluvoxamine[5]
- RR of disease progression, hospitalization = 0.71 vs 0.91 for ivermectin[5]
- fluvoxamine reduces composite of observation in a COVID-19 emergency setting for >6 hours or transfer to a tertiary hospital (RR=0.68)[9]
- 50 mg of fluvoxamine twice daily for 10 days does not improve time to recovery vs placebo[20]
- may reduce risk of clinical deterioration in outpatients with COVID-19[5]
- fluoxetine reduces mortality by 28%[11]
- fluoxetine or fluvoxamine reduces mortality 26%[11]
- any SSRI reduces mortality by 8%[11]
- fenofibrate allegedly reduces Covid-19 by up to 70%[6]
- lactoferrin may have efficacy for preventing infection
- experimental chewing gum contains ACE2 protein that attaches to SARS-CoV2 in saliva reducing salivary viral load by >95%[12]
Additional terms
References
- ↑ Frellick M First Pill for COVID-19 Could Be Ready by Year's End. Medscape - Mar 12, 2021. https://www.medscape.com/viewarticle/947376
- ↑ 2.0 2.1 Schoof M, Faust B, Saunders RA et al An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike. Science 18 Dec 2020. Vol. 370, Issue 6523, pp. 1473-1479 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33154106 PMCID: PMC7857409 Free PMC article https://science.sciencemag.org/content/370/6523/1473
- ↑ 3.0 3.1 Roy M Kaleido Biosciences Says Oral Drug Cuts COVID-19 Recovery Time, Hospitalizations. Medscape - Mar 24, 2021 https://www.medscape.com/viewarticle/948002 Kaleido Biosciences Reports Positive Results from Non-IND Study Demonstrating a Reduction in COVID-19 Related Healthcare Utilization and Recovery Time in Patients with Mild-to-Moderate COVID-19 and One or More Comorbidity. News Release. March 24, 2021 https://investors.kaleido.com/news-releases/news-release-details/kaleido-biosciences-reports-positive-results-non-ind-study
- ↑ 4.0 4.1 The Scripps Research Institute Extensive study identifies over a dozen existing drugs as potential COVID-19 therapies. MedicalXpress 2021. June 3 https://medicalxpress.com/news/2021-06-extensive-dozen-drugs-potential-covid-.html
- ↑ 5.0 5.1 5.2 5.3 Lenze EJ, Mattar C, Zorumski CF et al Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19A Randomized Clinical Trial. JAMA. Published online November 12, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33180097 https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2020.22760
Seymour CW, Bauchner H, Golub RM. COVID-19 Infection - Preventing Clinical Deterioration. JAMA. Published online November 12, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33180115
Sax P Could This Be Our First Effective, Inexpensive, Widely Available Outpatient Treatment for COVID-19? NEJM Journal Watch. HIV and ID Observations. August 12, 2021 https://blogs.jwatch.org/hiv-id-observations/index.php/could-this-be-our-first-effective-inexpensive-widely-available-outpatient-treatment-for-covid-19/2021/08/12/
Landhuis E Antidepressant Helps Prevent Hospitalization in COVID Patients: Study. Medscape August 27, 2021 https://www.medscape.com/viewarticle/957426
Reis G, dos Santos Moreira Silva EA, Medeiros Silva DC et al Effect of Early Treatment with Fluvoxamine on Risk of Emergency Care and Hospitalization Among Patients with COVID-19: The TOGETHER Randomized Platform Clinical Trial. medRxiv August 23, 2021 https://www.medrxiv.org/content/10.1101/2021.08.19.21262323v1 - ↑ 6.0 6.1 Gorman A Cholesterol-lowering drug being tested at Penn Medicine to help fight COVID-19. ABC Eyewitness News. 2021 August 10 https://abc7chicago.com/10943141/
- ↑ University of Michigan Study finds existing drugs that can kill SARS-CoV2 in cells. Medical X press. August 19, 2021 https://medicalxpress.com/news/2021-08-drugs-sars-cov2-cells.html
Mirabelli C, Wotring JW, Zhang CJ et al Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19. Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2105815118 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34413211 https://www.pnas.org/content/118/36/e2105815118 - ↑ 8.0 8.1 8.2 8.3 8.4 Bergman SJ COVID-19 Treatment: Investigational Drugs and Other Therapies. Mesdcape. August 18, 2021 https://emedicine.medscape.com/article/2500116-overview
- ↑ 9.0 9.1 Landhuis E Antidepressant May Cut COVID-Related Hospitalization, Mortality: TOGETHER Published. Medscape. October 28, 2021 https://www.medscape.com/viewarticle/961799
Reis G, dos Santos Moreira-Silva EA, Silva DCM et al Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. The Lancet Global Health. October 27, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34717820 PMCID: PMC8550952 Free PMC article https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext - ↑ 10.0 10.1 Pfizer Press Release. Nov 5, 2021 Pfizer's Novel COVID-19 Oral Antiviral Treatment Candidate Reduced Risk of Hospitalization or Death by 89% in Interim Analysis of Phase 2/3 EPIC-HR Study. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate
McNamara D FDA Authorizes Pfizer Antiviral Pill for COVID-19. Medscape. December 22, 2021 https://www.medscape.com/viewarticle/965398 - ↑ 11.0 11.1 11.2 11.3 Brooks M Growing Evidence Supports Repurposing Antidepressants to Treat COVID-19. Medscape. November 17, 2021 https://www.medscape.com/viewarticle/963136
Oskotsky T, Maric I, Tang A et al Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants. JAMA Netw Open. 2021;4(11):e2133090. Nov 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34779847 PMCID: PMC8593759 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786136 - ↑ 12.0 12.1 Crist C Experimental Chewing Gum Could Reduce Coronavirus Spread. Medscape. Novemember 24, 2021 https://www.medscape.com/viewarticle/963632
- ↑ Goodman B FDA Panel Backs First Pill for COVID-19 by a Small Margin. Medscape. November 30, 2021 https://www.medscape.com/viewarticle/963871
- ↑ Oskotsky T, Maric I, Tang A et al Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants. JAMA Netw Open. 2021;4(11):e2133090. Nov 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34779847 PMCID: PMC8593759 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786136
- ↑ 15.0 15.1 Halford B 4'-Fluorouridine fights respiratory viruses, including SARS-CoV-2, in animals. Chemical&Engineering News. December 9, 2021
Sourimant J, Lieber CM, Aggarwal M et al 4'-Fluorouridine is an oral antiviral that blocks respiratory syncytial virus and SARS-CoV-2 replication. Science. 2021 Dec 2:eabj5508. Online ahead of print. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34855509 - ↑ 16.0 16.1 Laday J Prophylaxis, treatment with probenecid inhibits 'virus replication' in COVID-19, flu, RSV. Helios. 2021. Sept 13. https://www.healio.com/news/rheumatology/20210910/prophylaxis-treatment-with-probenecid-inhibits-virus-replication-in-covid19-flu-rsv
- ↑ 17.0 17.1 McNamara D FDA Okays Emergency Use of Molnupiravir Pill for COVID-19. Medscape. December 23, 2021 https://www.medscape.com/viewarticle/965484
- ↑ 18.0 18.1 Cafardi J, Miller C, Terebelo H et al Efficacy and Safety of Pacritinib vs Placebo for Patients With Severe COVID-19. A Phase 2 Randomized Clinical Trial. JAMA Netw Open. 2022;5(12):e2242918. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36469321 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799198
- ↑ 19.0 19.1 Brevini T, Maes M, Webb GJ et al FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature 2022. Dec 5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36470304 https://www.nature.com/articles/s41586-022-05594-0
- ↑ 20.0 20.1 McCarthy MW, Naggie S, Boulware DR et al Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19A Randomized Clinical Trial. JAMA. 2023;329(4):296-305. Jan 12 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36633838 https://jamanetwork.com/journals/jama/fullarticle/2800448