Argentine researchers identified a therapeutic target for the chikungunya virus, which constitutes a starting point to be able to develop drugs against this disease, which currently has no specific treatment or vaccine, at the same time that they found candidate drugs that inhibited viral replication in the laboratory. CyTA Leloir Agency reported.
The results of our study constitute a starting point in the development of drugs against chikungunya, an encouraging advance if we consider that there are still no effective vaccines or therapies for this virus that is expanding worldwide in tropical and subtropical areas in recent 15 years, affirmed the doctor in Chemistry Mariela Bollini, who leads the Laboratory of Medicinal Chemistry of the Center for Research in Bionanosciences (Cibion) dependent on Conicet.
Currently, therapy for patients is limited to symptomatic treatment to mitigate the inflammation and pain caused by the viral infection.
The researchers led by Bollini worked with the E1 and E2 proteins of the chikungunya virus envelope that are involved in the invasion of host cells after the bite of an infected mosquito (Aedes aegypti and Aedes albopictus).
These proteins (analogous to the SARS-CoV-2 Spike) participate in the entry and release of the virus genome into the cell to initiate the multiplication program.
Using bioinformatic analyzes that reproduce the structure of the E1 and E2 proteins in 3D, the scientists identified a region in them that had the necessary characteristics to bind to molecules.
They then conducted a virtual screening of two commercial compound libraries and identified a candidate that, in in vitro studies, was able to inhibit virus replication in infected cells by nearly 100%.
Bollini, associate professor of Drug Design in the Bioengineering career at the Technological Institute of Buenos Aires (ITBA) said, the most active compound against chikungunya did not show considerable toxicity.
In addition, the researchers selected viral variants resistant to the antiviral action of the compound, which "is consistent with the proposed therapeutic target.
The work, published in the American Chemical Society Infectious Diseases https://pubs.acs.org/doi/10.1021/acsinfecdis.0c00915, represents a first step in the development of a drug that improves the characteristics of the identified compound.
Before evaluating this drug to be developed in humans, it would be necessary to do preclinical trials in laboratory animals.
Leandro Battini, first author and fellow of the Conicet in the Cibion also participated in the study; Daniela Fidalgo, from Cibion, and Diego Álvarez, from the Institute for Biotechnological Research (IIB-Intech), dependent on Unsam and Conicet.