A study by the Federal University of São Paulo (Unifesp) and by researchers from England and Italy highlighted a new action mechanism of medicine hepariin, an anticoagulant, in the treatment of coronaviruses (covid-19).
In addition to inhibiting bleeding disorders that can affect the pulmonary vessels and affect oxygenation, the drug also appears to be able to block the entry of the new coronavirus into cells. The researchers carried out laboratory tests on the kidney cell line of the African green monkey (Cercopithecus aethiops) and heparin reduced cell invasion by the new coronavirus by 70%.
In an interview with Agência Fapesp, Helena Bonciani Nader, Unifesp professor and project coordinator with the Brazilians, said there was evidence that heparin was also able to prevent viral infections, including by coronaviruses, but the evidence was not very solid . However, researchers have been able to prove this property of the drug in tests in vitro.
The researcher has been studying glycosaminoglycans for over 40 years - the class of complex carbohydrates to which heparin belongs - and has developed the first low molecular weight heparins, used clinically as anticoagulants and antithrombotics, including in patients with covid-19 .
One of the discoveries made during this period is that heparin is a multi-target drug, because in addition to its effect on preventing blood clotting, it can bind to various proteins. Among them are growth factors and cytokines that bind to specific receptors on the surface of target cells.
In recent years, studies by other groups have suggested that the surface proteins of other previously reported coronaviruses may bind to a glycosaminoglycan in mammalian cells, known as heparam sulfate, to infect them.
With the appearance of the new coronavirus, the Unifesp researchers had the idea of ??assessing whether the surface protein of the new coronavirus responsible for cell infection - called protein point - binds to heparin because the drug molecule has a structure very similar to that of heparan sulfate.
Experiments confirmed the hypothesis. Using surface plasmon resonance and circular dichroism spectroscopy, heparin, when linked to proteins, has been observed point of covid-19, causes a conformational change in these molecules. Thus, the "lock" for the virus to enter the cells malfunctions.The researchers also evaluated the structural forms of heparin that interact better and are able to modify the conformation of proteins. point new coronavirus, based on a library of derivatives and different fragments of the molecule, defined by size.
Now researchers are changing the structure of heparins to identify a molecule that has the same binding effect and the same change in conformation as the protein point of the new coronavirus, but which causes less bleeding - a potential side effect of the drug. In addition, they are also testing other compounds called mimic heparins - which mimic the action of heparin.