Fighting Zika Infections Using Widely Used Antibiotics
2015 was the year when many children were born with brain defects due to a worldwide outbreak of Zika virus. Lately, scientists from NIH have used a selection of advanced drug screening methods to examine more than 10,000 compounds searching for an antidote. Surprisingly, they discovered that methacycline – a widely used antibiotic, was potential in blocking brain infections and minimizing neurodevelopmental disorders linked to the virus in animal models. On top of that, they also identified that drugs formerly made to treat Alzheimer’s disease and inflammation might also help treat infections.
Avindra Nath, M.D., a senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke, a lead study author, stated that the outbreak of Zika created calamitous, indelible neurological issues for many kids and their families. Even though the infections are down, the risk remains. They anticipate that these promising outcomes of the study are a great milestone ahead of preparing for fighting the possible future outbreaks.
The research was collaboratively performed by researchers from Dr. Nath’s team and Anton Simeonov’s labs, and Radhakrishnan Padmanabhan, Ph.D., Professor at Georgetown University Medical Center.
Zika outbreak
Zika infection is caused by the Aedes aegypti mosquito. Around 60 nations reported zika virus infection between 2015 and 2016. In some countries, many infected mothers gave birth to babies with fetal microcephaly – a developmental brain disorder, where a baby’s head is much smaller than normal. Many other neuro disorders like Guillain-Barré syndrome, encephalitis, and myelitis were also reported in some infected people. Even with many scientists researching it, treatment or vaccine against the zika virus is yet to be developed.
Zika virus and existing antibiotics
Scientists analyzed different drugs that prevent the virus from replicating by inhibiting the activity of a protein known as NS2B-NS3 Zika virus protease. At the time of infection, the viral RNA is injected into a cell, leading to the synthesis of these viral proteins attached unitedly, side-by-side. The NS2B-NS3 protease then slices each protein that is crucial for assembling new viral particles.
Rachel Abrams, Ph.D., an organic chemist from Dr. Nath’s laboratory, and the study leader stated that proteases act like scissors, and for neutralizing many viruses – Blocking protease activity is a potential method. They wished to look broadly for medicines that could inhibit the protease from cutting the Zika virus polyprotein into its active components.
Dr. Abrams and scientists from Dr. Simeonov’s and Dr. Padmanabhan’s teams worked together to find a potential drug candidate to develop assays, or tests, for evaluating the efficacy of medications to obstruct NS2B-NS3 Zika virus protease activity. Every test was customized to a distinct screening or sifting method. Later, they then used these evaluations to simultaneously check thousands of candidates stored in 3 individual libraries.
With the outcomes of one of the preliminary screening of 2,000 compounds, it was revealed that widely used tetracycline-based antibiotic drugs, such as methacycline, may be potent at blocking the protease.
Later, extensive screening of 10,000 compounds revealed that an investigational anti-inflammatory medicine, known as MK-591, and a failed anti-Alzheimer’s disease drug, known as JNJ-404, are potential candidates against the Zika virus. Virtual screening (Artificial Intelligence-based programs) of more than 130,000 compounds was also utilized to identify the potential candidates.
Dr. Simeonov, scientific director at the NIH’s National Center for Advancing Translational Sciences, claimed that these study outcomes show that researchers can find treatments that can be repurposed for other diseases – using the benefits of the latest technological developments.
The stem cells in the brain are infected by the Zika virus. According to some researchers, this might be the reason why the Zika virus causes more harm to newborn babies than to adults. In vitro experiments on neural stem cells showed that methacycline, MK-591, and JNJ-404 are potential enough to fight the virus.
Tetracyclines are U.S. FDA certified drugs, and it has the ability to pass through the placenta of pregnant women, so the scientists concentrated on methacycline and ascertained that it might decrease few neurological developmental issues caused by the Zika virus. The tests in animal models showed that Zika-infected newborn mice that were treated with methacycline had better balance and could turn over more easily, but the mice which were administered with placebo has difficulties in balancing and turning over. As per the brain analysis, this was due to the antibiotic, as it lowered the infections and neural damage. However, the antibiotics didn’t totally prevent harm caused by the Zika virus. The weight of virus-infected mice was less than the control group regardless of whether the mice were given methacycline.
Dr. Abrams stated that the study on Fighting Zika Infections Using Widely Used Antibiotics shows that tetracycline-based antibiotics may at least be efficient at inhibiting neurological disorders concerned with Zika virus infections. And they hope that they can swiftly analyze their potentiality in clinical trials as these antibiotics are extensively available.
Fighting Zika Infections Using Widely Used Antibiotics
