Researchers at the Institute of Biomedical Sciences at the University of São Paulo (ICB-USP) have discovered seven drugs with the potential to inactivate the replication of the new coronavirus (SARS-CoV-2), which causes Covid-19.
The discovery was linked to a computational technique known as drug repositioning, which selected more than 11,000 drugs and identified the seven with the greatest capacity to prevent the replication of the coronavirus in infected cells (See list of drugs below).
The next step is to prove their effectiveness in vitro and, subsequently, in clinical trials in humans. The study was published in Journal of Biomolecular Structure and Dynamics.
According to Cristiane Guzzo, a professor at the ICB at USP and coordinator of the study, the seven drugs are already approved by the Food and Drug Administration (FDA), the regulatory agency in the United States, which may facilitate the advancement of research for clinical tests (in human cells ), if the effectiveness against the new coronavirus is proven in laboratory tests.
None of the drugs had been tested against Covid-19 so far, which may be an incentive for other researchers, says the specialist in structural biology. “The strategy of using these drugs is because they are already approved molecules and used in the market, and this makes it easier to achieve immediate use, since the entire process of validation, toxicity and side effects is established,” he told CNN.
The choice for the computational model known as QSAR, based on affinity prediction, avoided the need to carry out physical tests with thousands of drugs until reaching seven, making the study agile, explains the first author of the research, Anacleto Silva de Souza , biomolecular physicist and postdoctoral fellow at the ICB.
Of the 11,000 drugs that were contained in the DrugBank drug database, 2,500 were discarded. Of the remaining 8,500, 14 drugs for the treatment of migraine, respiratory diseases, antimicrobial action and natural products were selected for computer simulation until reaching those that showed greater affinity in inhibiting the proliferation of the new coronavirus, explains the study’s author.
“We developed three mathematical models by which we ranked the drugs and selected the most promising ones, which represented the best affinity for predilection,” Souza told CNN.
Focus is on preventing coronavirus replication
By computer, the researchers tested the action of 11,000 drugs on the 3CLpro enzyme of SARS-CoV-2, responsible for virus replication, and selected those that showed greater affinity in deactivating the enzyme and, consequently, preventing the coronavirus from becoming replicate in other cells.
The study hypothesis simulates that, by inactivating the action of 3CLpro, the virus stops replicating and proliferating, resulting in a decrease in viral load and preventing Covid-19 from becoming serious.
The choice to focus on the action of the coronavirus enzyme 3CLpro differed from other studies, many of them focused on the protein spike. SARS-CoV-2 enters the cell when its spike protein binds to the angiotensin-2 converting enzyme receptor (called ACE2) on the cell surface. “SARS-Cov-2 uses our own cells to produce more virus, and we’re trying to inhibit the virus from replicating,” Guzzo said.
Some Covid-19 vaccines use inactivated parts of the spike protein in their composition.
If the thesis is proven in vitro, the same drugs could be tested in human cells to find out if, in fact, they could be used as a treatment against Covid-19 in the future. But the researchers say that it is still necessary to have the results of in vitro tests to know whether tests in humans will be viable.
“These are promising drugs, because we have data that suggest they will be effective, but we need to prove it experimentally, and even then that doesn’t mean it will work in humans. There is no way to prescribe any medication”, emphasizes the researcher.
List of promising drugs
- Hexasaccharide derived from acarbose (natural product);
- Angiotensinamide (vasoconstrictor);
- Dihydrostreptomycin (antibiotic);
- Envomycin (antibiotic);
- Fenotrol (Fenoterol hydrobromide is indicated for the symptomatic treatment of acute asthma attacks and chronic obstructive bronchitis);
- Naratriptan (used in the acute treatment of migraine attacks);
- Viomycin (antibiotic).