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An Update on SARS-CoV-2 Clinical Trial Results-What We Can Learn for the Next Pandemic
Benediktus Yohan Arman1,2, Juliane Brun1,2, Michelle L Hill3
1Antiviral Drug Discovery Unit, Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Abstract:
The coronavirus disease 2019 (COVID-19) pandemic has claimed over 7 million lives worldwide, providing a stark reminder of the importance of pandemic preparedness. Due to the lack of approved antiviral drugs effective against coronaviruses at the start of the pandemic, the world largely relied on repurposed efforts. Here, we summarise results from randomised controlled trials to date, as well as selected in vitro data of directly acting antivirals, host-targeting antivirals, and immunomodulatory drugs. Overall, repurposing efforts evaluating directly acting antivirals targeting other viral families were largely unsuccessful, whereas several immunomodulatory drugs led to clinical improvement in hospitalised patients with severe disease. In addition, accelerated drug discovery efforts during the pandemic progressed to multiple novel directly acting antivirals with clinical efficacy, including small molecule inhibitors and monoclonal antibodies. We argue that large-scale investment is required to prepare for future pandemics; both to develop an arsenal of broad-spectrum antivirals beyond coronaviruses and build worldwide clinical trial networks that can be rapidly utilised.
Insights
Repurposing existing drugs for COVID-19 showed limited success, but new antivirals and immunomodulators proved effective. Future pandemic preparedness requires investment in broad-spectrum antivirals and global clinical trial networks.
Area of Science:
- Virology
- Infectious Diseases
- Pharmacology
Background:
- The COVID-19 pandemic highlighted the urgent need for effective treatments.
- Initial pandemic response heavily relied on drug repurposing due to a lack of specific antivirals.
- Over 7 million lives were lost globally, emphasizing pandemic preparedness.
Purpose of the Study:
- To summarize the efficacy of repurposed and novel drugs against coronaviruses.
- To evaluate directly acting antivirals, host-targeting antivirals, and immunomodulatory drugs.
- To inform future pandemic preparedness strategies.
Main Methods:
- Systematic review of randomized controlled trials.
- Inclusion of selected in vitro data for antiviral drug evaluation.
- Analysis of repurposed drugs and novel drug discovery efforts.
Main Results:
- Repurposing direct-acting antivirals from other viral families was largely unsuccessful.
- Immunomodulatory drugs demonstrated clinical improvement in hospitalized severe COVID-19 patients.
- Accelerated discovery yielded novel direct-acting antivirals, including small molecules and monoclonal antibodies.
Conclusions:
- Significant investment is needed for future pandemic preparedness.
- Development of broad-spectrum antivirals beyond coronaviruses is crucial.
- Establishing rapidly deployable worldwide clinical trial networks is essential.
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