Lack of efficacy of mono‐mode of action therapeutics in COVID‐19 therapy ‐ How the lack of predictive power of preclinical cell and animal studies leads developments astray
Open Access
- 31 October 2021
- journal article
- research article
- Published by Wiley in Chemical Biology & Drug Design
- Vol. 99 (1), 32-45
- https://doi.org/10.1111/cbdd.13954
Abstract
The diverse experiences regarding the failure of tested drugs in the fight against COVID-19 made it clear that one should at least question the requirement to apply classical preclinical development strategies that demand cell and animal efficacy models to be tested before going into clinical trials. Most animals are not susceptible to infection with SARS-CoV-2, and so this led to one-sided virus replication experiments in cells and the use of animal models that have little in common with the complex pathogenesis of COVID-19 in humans. Therefore, non-clinical development strategies were designed to meet regulatory requirements, but they did not truly reflect the situation in the clinic. This has led the search for effective agents astray in many cases. As proof of this statement, we now bring together the results of such required preclinical experiments and compare with the results in clinical trials. Two clear conclusions that can be drawn from the experience to date: The required preclinical models are unsuitable for the development of innovative treatments medical devices in the case of COVID-19 and mono-action strategies (e.g. direct antivirals) are of very little or no benefit to patients under randomised-blind conditions. Our hypothesis is that the complex situation of COVID-19 may benefit from multi-mode drugs. Here, the molecular class of aptamers could be a solution.Keywords
This publication has 87 references indexed in Scilit:
- COVID-19: the new challenge for rheumatologistsClinical and Experimental Rheumatology, 2020
- 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)Clinical Infectious Diseases, 2020
- Van der Waals thin films of WTe2 for natural hyperbolic plasmonic surfacesNature Communications, 2020
- Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methodsActa Pharmaceutica Sinica. B, 2020
- Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitroCell Research, 2020
- Protective Effects of Hydroxychloroquine against Accelerated Atherosclerosis in Systemic Lupus ErythematosusMediators of Inflammation, 2018
- Aptamer BC 007 – A broad spectrum neutralizer of pathogenic autoantibodies against G-protein-coupled receptorsEuropean Journal of Pharmacology, 2016
- Designing Anti-Influenza Aptamers: Novel Quantitative Structure Activity Relationship Approach Gives Insights into Aptamer – Virus InteractionPLOS ONE, 2014
- G-quadruplex DNA Aptamers and their Ligands: Structure, Function and ApplicationCurrent Pharmaceutical Design, 2012
- A DNA Aptamer Prevents Influenza Infection by Blocking the Receptor Binding Region of the Viral HemagglutininOnline Journal of Public Health Informatics, 2004