Since the beginning of the COVID-19 pandemic, there has been a strong drive and desire to find effective treatments for and protection against the disease. On the webpage ClinicalTrials.gov, a total of 6505 clinical trials currently (September 2021) investigating various aspects of COVID-19 are registered. Of these, 124 studies involving peptides were identified. These 124 were further evaluated, and 88 trials that used peptides only for routine diagnostics were excluded. The remaining 36 trials were classified into 5 different classes according to their function: immunomodulatory (5 trials), regain homeostasis (10 trials), diagnostics/biomarkers (8 trials), vaccination (9 trials), and antiviral activity (4 trials, all overlap with immunomodulatory activities). In the current review, these 36 trials are briefly described and tabularly summarised. According to the estimated finish date, 14 trials have not yet finished. All of the finished trials are yet to report their results. Seven trials were based in the USA, and Egypt, France, the UK, Turkey, and the Russian Federation conducted three trials each. This review aims to present a snapshot of the current situation of peptides in COVID-19 clinical trials and provides a template to follow up on trials of interest; it does not claim to be a complete overview.
Title | Peptide | Function | Status | Country | Reference |
---|---|---|---|---|---|
Efficacy and Safety of Lactoferrin as an Adjunct Therapeutic Agent for COVID-19 | Peptides derived by proteolytic cleavage of lactoferrin | Antiviral and immunomodulatory | Estimated completion: November 2020, no update | Egypt | [50] |
Efficacy of Lactoferrin as a Preventive Agent for Healthcare Workers Exposed to COVID-19 | Peptides derived by proteolytic cleavage of lactoferrin | Antiviral and immunomodulatory | Estimated completion: November 2020, no update | Egypt | [51] |
The Clinical Trial of Application of Ezrin Peptide (HEP-1) for Treatment of Coronavirus Disease (COVID-19) Infection | Human ezrin peptide 324-337, HEP1 (TEKKRRETVEREKE) | Antiviral and immunomodulatory | Estimated completion: April 2021, no update | Iran | [48] |
Efficacy and Safety of Ovotransferrin in COVID-19 Patients With Mild-to-Moderate Disease | Peptides derived by proteolytic cleavage of ovotransferrin | Antiviral and immunomodulatory | Estimated completion: March 2021, no update | Italy | [54] |
B-natriuretic Peptide (BNP), Serum Troponin-I, and D-dimer as Risk Factors for In-hospital Death in Patients With COVID-19 | N-terminal pro B type natriuretic peptide (NTproBNP, MDPQTAPSRALLLLLFLHLAFLGGRSHPLGSPGSASDLETSGLQEQRNHLQGKLSELQVEQTSLEPLQESPRPTGV) | Diagnostic/biomarker | Estimated completion: September 2021, no update | Egypt | [24] |
N-terminal Pro B-type Natriuretic Peptide and Vitamin D Levels as Prognostic Markers in COVID-19 Pneumonia | N-terminal pro B type natriuretic peptide (NTproBNP, MDPQTAPSRALLLLLFLHLAFLGGRSHPLGSPGSASDLETSGLQEQRNHLQGKLSELQVEQTSLEPLQESPRPTGV) | Diagnostic/biomarker | Estimated completion: January 2021, no update | Egypt | [25] |
Cardiac Biomarkers and Mortality in Critically Ill Patients With SARS-CoV-2 (COVID-19): COROBIOCHIC | N-terminal pro B type natriuretic peptide (NTproBNP, MDPQTAPSRALLLLLFLHLAFLGGRSHPLGSPGSASDLETSGLQEQRNHLQGKLSELQVEQTSLEPLQESPRPTGV) | Diagnostics/biomarker | Completed in June 2020, no update | France | [30] |
Incidence, Risk Factors and Prognosis of Pulmonary Fibrosis During Severe COVID-19 Pneumonia | amino-terminal type I (PINP) and type III (PIIINP) peptides of procollagen | Diagnostics/biomarker | Estimated completion: December 2021 | France | [36] |
Prospective, One Center, Four Groups, Open, Comparative, Controlled Study to Explore T Cells Response to SARS COV 2 Peptides by Metabolic Activity Method in Convalesce and Healthy Individuals Versus Antibody Response | undefined SARS-CoV-2 peptides | Diagnostics/biomarker | Estimated completion: October 2021 | Israel | [32] |
[68Ga]Ga-DOTA-(RGD)2 PET/CT Imaging of Activated Endothelium in Lung Parenchyma of COVID-19 Patients | [68Ga]Ga-DOTA-(RGD)2 | Diagnostics/biomarker | Estimated completion: May 2022 | Netherlands | [35] |
Investigating Cytokine Storm Biomarkers in Children Presenting to Acute Paediatric Services (Non-intensive Care) With Paediatric Inflammatory Multisystem Syndrome During the Covid-19 Pandemic. An Observation Study | N-terminal pro B type natriuretic peptide (NTproBNP, MDPQTAPSRALLLLLFLHLAFLGGRSHPLGSPGSASDLETSGLQEQRNHLQGKLSELQVEQTSLEPLQESPRPTGV) | Diagnostics/biomarker | Estimated completion: December 2021 | UK | [31] |
18F-αvβ6-binding-peptide PET/CT in Patients Post SARS CoV2 Infection | [18F]-αvβ6 binding peptide | Diagnostics/biomarker | Estimated completion: May 2022 | USA | [34] |
A Single-arm, Open-Label, Phase II Clinical Study to Evaluate the Safety and Efficacy of Thymic Peptides in the Treatment of Hospitalized COVID-19 Patients in Honduras | thymic peptides, composition and source unknown | Immunomodulatory | Completed in May 2021, no update | Honduras | [3] |
Aerosol Inhalation of the Exosomes Derived From Allogenic COVID-19 T Cell in the Treatment of Early Stage Novel Coronavirus Pneumonia | peptide fragments of the COVID-19 proteome | Immunomodulatory | Estimated completion: May 2021, no update | Turkey | [9] |
A Pilot Trial of Thymalfasin (Ta1) to Prevent COVID-19 Infection in Renal Dialysis Patients) | thymosin-alpha 1 (Ac-SDAAVDTSSEITTKDLKEKKEVVEEAEN) | Immunomodulatory | Estimated completion: May 2022 | USA | [5] |
A Pilot Trial of Thymalfasin (Ta1) to Treat COVID-19 Infection in Patients With Lymphocytopenia | thymosin-alpha 1 (Ac-SDAAVDTSSEITTKDLKEKKEVVEEAEN) | Immunomodulatory | Estimated completion: June 2021 | USA | [6] |
Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study of LSALT Peptide as Prevention of Acute Respiratory Distress Syndrome (ARDS) and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19) | LSALT (LSALTPSPSWLKYKAL) | Immunomodulatory | Estimated completion: June 2021, no update | USA, Canada, Turkey | [8] |
Angiotensin-(1,7) Treatment in COVID-19: the ATCO Trial | angiotensin peptide (1-7) (DRVYIHP) |
Restoring homeostasis | Estimated completion: June 2023 | Belgium | [12] |
Randomized Clinical Trial Phase I/II for the Use of Angiotensin-(1-7) in the Treatment of Severe Infection by Sars-CoV-2 | angiotensin peptide (1-7) (DRVYIHP) |
Restoring homeostasis | Estimated completion: December 2021 | Brazil | [13] |
FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia | fibrin-derived peptide beta15-42 | Restoring homeostasis | Completed in June 2021, no update | France | [21] |
Evaluation of the Possible Role of Angiotensin Peptide (1-7) on Treatment of COVID-19 | angiotensin peptide (1-7) (DRVYIHP) |
Restoring homeostasis | Estimated completion: September 2020, no update | Turkey | [11] |
A Comparative, Multicenter, Placebo-Controlled, Double-Blind Phase II Clinical Trial Evaluating the Efficacy, Safety and Tolerability of Inhaled Aviptadil in Patients 18 Years and Older With COVID-19 Pulmonary Involvement - HOPE | Aviptadil, a vasoactive intestinal peptide (VIP), analogue, inhalable | Restoring homeostasis | Estimated completion: December 2022 | Turkey | [19] |
Investigating the Relationship Between the Renin Angiotensin System and the Coagulopathy Associated With COVID-19 | TRV027, a modified angiotensin peptide (1-7) (XRVYIHPA; X stands for sarcosine (Sar), and the C-terminal alanine residue has a hydroxy group) |
Restoring homeostasis | Completed in May 2021, no data available yet | UK | [14] |
CONNECTS Master Protocol for Clinical Trials Targeting Macro-, Micro-immuno-thrombosis, Vascular Hyperinflammation, and Hypercoagulability and Renin-angiotensin-aldosterone System (RAAS) in Hospitalized Patients With COVID-19 (ACTIV-4 Host Tissue) | TRV027 and TXA127, (TRV027:XRVYIHPA; X stands for sarcosine (Sar), and the C-terminal alanine residue has a hydroxy group), TXA127: pharmaceutical formulation of the natural angiotensin peptide (1-7) DRVYIHP) |
Restoring homeostasis | Estimated completion: December 2022 | USA | [15] |
ZYESAMI (Aviptadil) for the Treatment of Critical COVID-19 With Respiratory Failure | Aviptadil (HSDAVFTDNYTRLRKQMAVKKYLNSILN), a vasoactive intestinal peptide (VIP), analogue, intravenously administered | Restoring homeostasis | Completion: February 2021 | USA | [20] |
A Randomized, Double-Blind, Placebo-Controlled, Two-Part Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, PK, & PD of RLS-0071 in Patients With Acute Lung Injury Due to COVID-19 Pneumonia in Early Respiratory Failure | RLS-0071 (IALILEPICCQERAA-dPEG24) | Restoring homeostasis | Estimated completion: July 2021 | USA | [23] |
A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With Acute Respiratory Distress Syndrome Associated With COVID-19 | vasoactive intestinal peptide (VIP: HSDAVFTDNYTRLRKQMAVKKYLNSILNG and other drugs) | Restoring homeostasis | Estimated completion: April 2023 | Various | [18] |
A Randomized, Open Label, Phase 1 Study to Evaluate the Safety, Reactogenicity and Immunogenicity of OSE-13E, a Multiepitope-based Vaccine Candidate Against COVID-19, in Healthy Adults (COVEPIT-3) | T-cell epitopes from 11 different proteins of SARS-CoV-2 | Vaccination | Estimated completion: March 2022 | Belgium | [39] |
P-pVAC-SARS-CoV-2: Phase I Single-center Safety and Immunogenicity Trial of Multi-peptide Vaccination to Prevent COVID-19 Infection in Adults | a mixture of undefined peptides | Vaccination | Estimated completion: December 2021 | Germany | [37] |
B-pVAC-SARS-CoV-2: Phase I/II Multicenter Safety and Immunogenicity Trial of Multi-peptide Vaccination to Prevent COVID-19 Infection in Adults With Bcell/ Antibody Deficiency | a mixture of undefined peptides | Vaccination | Estimated completion: December 2021 | Germany | [38] |
Simple, Blind, Placebo-controlled, Randomized Study of the Safety, Reactogenicity and Immunogenicity of Vaccine Based on Peptide Antigens for the Prevention of COVID-19 (EpiVacCorona), in Volunteers Aged 18-60 Years (I-II Phase) | chemically synthesised peptides are antigens of SARS-CoV-2 proteins, undefined | Vaccination | Estimated completion: May 2021, no update | Russian Federation | [43] |
An Open Study of the Safety, Reactogenicity and Immunogenicity of the Vaccine Based on Peptide Antigens for the Prevention of COVID-19 (EpiVacCorona), With the Involvement of Volunteers Aged 60 Years and Above (Phase III-IV) | chemically synthesised peptides are antigens of SARS-CoV-2 proteins, undefined | Vaccination | Estimated completion: January 2021, no update | Russian Federation | [44] |
Multicenter Double-blind Placebo-controlled Comparative Randomized Study of the Tolerability, Safety, Immunogenicity and Prophylactic Efficacy of the EpiVacCorona Peptide Antigen-based Vaccine for the Prevention of COVID-19, With the Participation of 3000 Volunteers Aged 18 Years and Above (Phase III-IV) | chemically synthesised peptides are antigens of SARS-CoV-2 proteins, undefined | Vaccination | Estimated completion: January 2021, no update | Russian Federation | [45] |
A Phase I, Open-label Study to Evaluate the Safety, Tolerability, and Immunogenicity of UB-612 Vaccine in Healthy Adult Volunteers | Th/CTL epitope peptide pool | Vaccination | Estimated completion: May 2021, no update | Taiwan | [40] |
A Phase II, Placebo-controlled, Randomized, Observer-blind Study to Evaluate the Immunogenicity, Safety, and Tolerability of UB-612 Vaccine Against COVID-19 in Adolescent, Younger and Elderly Adult Volunteers | Th/CTL epitope peptide pool | Vaccination | Estimated completion: May 2021, no update | Taiwan | [41] |
Characterisation of the Immune Response to SARS-CoV-2 Infection | overlapping peptides from the SARS-CoV-2 proteome | Vaccination | Estimated completion: December 2023 | UK | [42] |
This entry is adapted from the peer-reviewed paper 10.3390/biologics1030018