Why repurposing is the only option in an emergency.
On average, it takes over 13 years to develop a new drug. In April 2020, there was no time for that. Three key points about the repurposing approach:
Repurposing refers to the use of drugs that have already been developed and, in some cases, approved for other conditions—but are now being tested for their effectiveness against a new pathogen.
Repurposing candidates have already undergone basic nonclinical safety testing—and have safety profiles based on human use.
This significantly speeds up the approval process—provided that randomized controlled trials (RCTs) demonstrate efficacy and safety in the new context.
The 8 Strategies for Pharmaceutical Intervention.
In 2020, scientists around the world worked around the clock to develop antiviral treatments for SARS-CoV-2. These approaches were pursued in parallel:
The SARS-CoV-2 genome and specific proteins.
Based on detailed knowledge of the genome and the proteins it encodes, specific targets for drug candidates were identified.
Virus entry and replication.
Findings regarding the nature of the viral infection and SARS-CoV in vitro provided initial clues as to effective inhibitors.
Computer-generated molecular models.
In silico methods made it possible to quickly identify potential drug-protein interactions even before laboratory testing.
In vitro findings for approved substances.
Known substances were tested for efficacy against SARS-CoV-2 in cell culture models—including remdesivir and chloroquine.
Repurposing approved antiviral drugs.
Drugs already approved for other RNA viral infections have been tested for efficacy against COVID-19—the classic drug repurposing approach.
Repurposing clinically tested, unapproved substances.
Candidates in clinical trials that have not yet received full approval—quickly accessible through compassionate use or hardship programs.
Findings from SARS-CoV and MERS-CoV.
Clinical experience from the 2002–2003 outbreaks and MERS provided valuable insights into treatment approaches and their limitations.
Convalescent plasma.
Plasma from recovered COVID-19 patients containing neutralizing antibodies has been tested in initial case series involving critically ill patients.
The candidates in April 2020.
In 2020, four substances were the primary focus of repurposing research against SARS-CoV-2:
Remdesivir – Originally developed to treat Ebola, it inhibited the SARS-CoV-2 RNA polymerase in vitro. Initial reports from U.S. hospitals showed promising results. The BfArM approved a compassionate use program.
Chloroquine / Hydroxychloroquine – The antimalarial drug inhibited viral replication in cell cultures. At the same time, health authorities warned of serious cardiac arrhythmias. Clinical trials were halted.
Favipiravir (T-705) – Approved for influenza, it inhibited the RNA polymerase of several RNA viruses, including SARS-CoV-2, in vitro. Clinical evidence was still pending.
Lopinavir/Ritonavir & Camostat Mesilate – Both inhibit proteases that are essential for viral replication. Camostat also inhibits TMPRSS2 – the cellular protease that SARS-CoV-2 activates to enter lung cells.
“In vitro ≠ clinical efficacy. What was seen as a promising development in 2020 had to prove itself in randomized trials—and not everything passed the test.”
Update 2025: What became of it.
Five years after this article was published, it is time to take stock:
Remdesivir was approved by the FDA in October 2020 as the first COVID-19 drug (Veklury®). In hospitalized patients requiring oxygen, it significantly shortened the recovery time.
Chloroquine and hydroxychloroquine failed in large controlled trials (including the WHO Solidarity Trial). A lesson in the difference between in vitro data and clinical reality—and in the danger of political pressure on regulatory approval processes.
Favipiravir has shown limited evidence of efficacy in mild to moderate cases. It is used in Japan and some other countries, but has not received broad international approval.
Lopinavir/ritonavir showed no clinical benefit in the WHO Solidarity Trial and was removed from most treatment protocols.
New successes in drug repurposing since 2020: Dexamethasone has proven to be one of the most effective approaches to date. Paxlovid (nirmatrelvir/ritonavir, 2021) builds on insights from drug repurposing related to protease inhibitors.
Three Lessons for Pandemic Preparedness.
What the pharmaceutical industry and regulators should take away from the COVID-19 drug repurposing experience:
In vitro ≠ clinical efficacy.
Cell culture data are a starting point, not proof. Chloroquine is the most painful example of how political pressure can lower the bar for scientific evidence.
RCTs remain the gold standard.
Even under extreme time pressure, randomized controlled trials remain indispensable. The WHO Solidarity Trial was the most important example of international coordination during a pandemic.
Regulatory flexibility requires structures.
Compassionate use and conditional approvals work—but only if the necessary framework is in place beforehand. Pandemic preparedness means putting these structures in place before the next crisis strikes.
