Not just vaccines to avoid getting sick with Covid-19. Scientists are also on the hunt for drugs that can cure it, and in what is defined as the most comprehensive study ever conducted on the front of pharmacological ‘repositioning’ – that is, the identification of compounds that are already used or being studied against other diseases , but they could be useful in fighting the coronavirus – researchers at the American Scripps Research Institute have identified “90 existing drugs or drug candidates” with antiviral action against the pandemic coronavirus.
Of these, they explain in ‘Nature Communications’, “13 have the potential to be repurposed as anti-Covid therapies”. Among the latter, “4 are drugs already approved” for other indications (halofantrine, nelfinavir, simeprevir and manidipine) and “9 are compounds in other development stages, with strong potential to be re-proposed as oral drugs” against Covid-19. Out of the total of 90 identified as capable of preventing Sars-CoV-2 from replicating in human cells, “19 can act in concert with remdesivir”, an antiviral already authorized for Covid, “or by enhancing its action”.
The work – the results of which are available online at reframedb.org – is the result of a collaboration between Calibr, a division of the Scripps Research Institute dedicated to drug discovery, and a team from the Institute’s Department of Immunology and Microbiology. The authors tested the more than 12 thousand molecules of the ReFrame ‘library’ on two types of human cells infected with the pandemic coronavirus, which contains products already approved by the US regulatory agency Fda and other experimental compounds tested for safety of use in humans. A ‘maxi archive’ created in 2018 by Calibr with the support of the Bill & Melinda Gates Foundation, with the aim of ‘filing’ possible therapies against neglected tropical diseases or other pathologies without treatment.
“Even though we have effective vaccines against Covid-19, we still lack highly effective antiviral drugs that can prevent the infection or prevent it from getting worse,” said Peter Schultz, president and CEO of the Scripps Research Institute. “Our results – he underlines – increase the feasible ways to reuse existing oral drugs with efficacy against Sars-CoV-2”. But not only: “We are also exploiting the data obtained to develop potentially more effective optimized antivirals” against the pandemic coronavirus, “including its variants and drug resistant strains, as well as against other coronaviruses already circulating or that could emerge in the future”.
“Some of the antiviral strategies that have proved most effective are ‘cocktails’ of different drugs such as those used against HIV infections,” said Thomas Rogers, corresponding author of the study. “The potential benefit of a combination of drugs is that taking a lower dose of any drug can reduce the risk of side effects from that single compound,” said lead author Malina Bakowski.
Based on what was observed in cell cultures, the scientists tested the best performing candidates on human tissue cells and an animal model. “The results from cell and animal model tests are very promising,” Schultz comments. “The need for medical treatment to tackle Covid-19 remains,” he reiterates. But “it is essential to proceed with the utmost rigor to determine what is safe and effective. This – he warns – is the most appropriate path to find new therapies that will make a difference for patients”.