A Fiocruz research has observed that the drug Atazanavir, used against HIV, was able to inhibit viral replication and to reduce the production of proteins that are related to the inflammatory process in the lungs, and therefore to the worsening of the clinical symptoms of the disease. Specialists have also looked into the combined use of atazanavir and ritonavir, another drug used to fight HIV.
The study was published this Monday (April 6) on the BiorXiv international plataform, in preprint version, following the trend of the study and of the repositioning of drugs in the battle against this public health emergency. “The analysis of drugs already approved for other uses is the fastest strategy science can provide to help fight the covid-19, together with the adoption of social distancing protocols already in place”, says Thiago Moreno, Fiocruz researcher, in charge of the initiative.
Moreno highlights that the drugs proposed by the World Health Organization (WHO) are closer to becoming treatments for covid-19 patients. However, he observes that more alternatives are necessary, especially substances already produced in the country and with a superior safety profile when compared to some of the molecules initially proposed by WHO. He also emphasizes the risks of self-medication, as each patient should be assisted by their physician, who should follow the patient’s treatment especially in the event of new diseases and repositioned drugs.
The research, coordinated by the Center for Technological Development in Health (CDTS/Fiocruz), involves scientists of the Oswaldo Cruz Institute (IOC/Fiocruz), including these laboratories: Respiratory Viruses and Measles, Immunopharmacology, Molecular Biology, and Endemic Diseases, and the Laboratory of Research on Thymus, as well as the Evandro Chagas National Institute for Infectious Deseases (INI/Fiocruz), the Research Institute D’Or, and the Iguaçu University.
Molecular modeling and tests on cells
Considering that previous scientific studies had already identified the Mpro viral proteasis, an enzyme that allows viral proteins to be produced correctly, as a central target in the search for drugs against the new coronavirus, researchers have turned their gaze to the potential of atazanavir.
In addition to acting on the Mpro, there is also evidence that this drug works on the respiratory tract itself, which drew the attention of scientists during the phase of selecting substances to be investigated.
Researchers carried out three types of tests: they observed the molecular interaction of atazanavir and the specific region of the Sars-CoV-2 in question (the Mpro), they experimented with this enzyme, and tested the drug on in vitro infected cells. Comparative experiments were also carried out with chloroquine, which has been included in several clinical trials worldwide. In this case, the results obtained only with atazanavir and with atazanavir and ritonavir were better than those observed with chloroquine, which motivates the team to advance in these studies.
From the point of view of the national production of the drug, in a context of possible adoption of the drug as clinical strategy, it is important to emphasize the fact that the Drug Technology Institute of Fiocruz (Farmanguinhos/Fiocruz) is in charge of the national production of these drugs.