The Fight-nCoV consortium was formed with the goal of developing new antiviral drugs to fight against SARS-CoV-2, the virus that causes COVID-19. Different classes of novel antivirals discovered in our laboratories were examined. For these compounds, a line of biological tests of increasing complexity was established, starting with laboratory tests, progressing to small animals, and finally to monkeys.
In the first phase of our collaborative project, a laboratory test was established, known as an in vitro screening assay, to evaluate the effectiveness of new antiviral drug candidates. The test was developed using different types of SARS-CoV-2 virus, such as Wuhan and variants of concern, as well as using different models in cell lines and primary lung epithelial cells. In these assays, we identified several molecules that turned out to be highly active and protective, even against other viral families.
Before entering animal tests (in vivo), the most active drug candidates were tested in mice to determine their level of toxicity and pharmacokinetic profiles. The second phase started with the development of a SARS-CoV-2 model in mice and hamsters.
Finally, a SARS-CoV-2 challenge model was established in small monkeys (non-human primates) that have a physiology much closer to human beings than mice or hamsters. The success of establishing a SARS-CoV-2 model in non-human primates was reported in the journal Nature in July 2020, just four months after the start of the program.
Based on all previous test results, two antiviral compounds, the molecular tweezer CP019 and a protease inhibitor were selected for the third test phase in macaques. To improve delivery in the respiratory tract, an aerosol process for drug administration was developed.
The Fight-nCoV project also evaluated an old antiviral drug, hydroxychloroquine. However, hydroxychloroquine did not show any effect against SARS-CoV-2 in non-human primate studies. By contrast, the molecular tweezer CP019 showed potential as an antiviral agent in several of the test animals, and is currently under further development and optimization, especially with respect to its improved formulation and dosing. We conclude that the development of an intranasal spray for the treatment of respiratory tract infections is possible.
Fight-nCoV partners have published 42 peer-review articles in open access and several in very high-impact journals. The partners have also actively participated in scientific meetings, workshops, TV, radio, and other media. Patent applications were submitted for two different classes of broad-spectrum antiviral compounds for further exploitation.
The clinical feasibility and development plans were evaluated and it can be concluded that the development of an intranasal spray for the treatment of respiratory tract infections is feasible. It is conceivable that the development of a broad-spectrum antiviral to be used to curb a pandemic threat is initially developed for the treatment of one respiratory tract infection with a recurrent epidemic occurrence and medical need that at the same time can be evaluated in a viral challenge model of healthy adult volunteers who does not risk getting a severe disease (examples RSV and influenza). The license and building production capacities as well as marketing for a broad-spectrum antiviral to treat one virus infection will facilitate the extension of treatment indications to other virus infections and enables kick-starting of new clinical trials when required. Altogether, the Fight-nCoV project has identified new broad-spectrum antivirals that have the potential to be developed further for clinical use.
