A widely used antibiotic methacycline was shown effective at preventing brain infections and reducing neurological problems associated with Zika virus in mice models.
National Institutes of Health (NIH) researchers used advanced drug screening techniques to test out more than 10,000 compounds in search of Zika virus therapeutics. The scientists discovered that the widely used antibiotic methacycline was effective at preventing brain infections and reducing neurological problems associated with the virus in mice. Additionally, they found that drugs originally designed to combat Alzheimers disease and inflammation may also help fight infections.
In this study, the researchers looked for drugs that prevent the virus from reproducing by blocking the activity of a protein called NS2B-NS3 Zika virus protease. The Zika virus is a protein capsule that carries long strings of RNA-encoded instructions for manufacturing more viral proteins. During an infection, the virus injects the RNA into a cell, resulting in the production of these proteins, which are strung together, side-by-side, like the parts in a plastic model airplane kit. The NS2B-NS3 protease then snaps off each protein, all of which are critical for assembling new viral particles.
The study was a collaboration between scientists on Dr. Naths team and researchers in laboratories led by Anton Simeonov, Ph.D., scientific director at the NIHs National Center for Advancing Translational Sciences (NCATS) and Radhakrishnan Padmanabhan, Ph.D., Professor of Microbiology & Immunology, Georgetown University Medical Center, Washington, D.C.
The Zika virus is primarily spread by the Aedes aegypti mosquito. In 2015 and 2016, at least 60 countries reported infections. Some of these countries also reported a high incidence of infected mothers giving birth to babies born with abnormally small heads resulting from a developmental brain disorder called fetal microcephaly. In some adults, infections were the cause of several neurological disorders including Guillain-Barr syndrome, encephalitis, and myelitis. Although many scientists have tried, they have yet to discover an effective treatment or vaccination against the virus.
Proteases act like scissors. Blocking protease activity is an effective strategy for counteracting many viruses, said Rachel Abrams, Ph.D., an organic chemist in Dr. Naths lab and the study leader. We wanted to look as far and wide as possible for drugs that could prevent the protease from snipping the Zika virus polyprotein into its active pieces.
To find candidates, Dr. Abrams worked with scientists on Dr. Simeonovs and Dr. Padmanabhans teams to create assays, or tests, for assessing the ability of drugs to block NS2B-NS3 Zika virus protease activity in plates containing hundreds of tiny test tubes. Each assay was tailored to a different screening, or sifting, technique. They then used these assays to simultaneously try out thousands of candidates stored in three separate libraries.
One preliminary screen of 2,000 compounds suggested that commonly used, tetracycline-based antibiotic drugs, like methacycline, may be effective at blocking the protease.
Meanwhile, a large-scale screen of more than 10,000 compounds helped identify an investigational anti-inflammatory medicine, called MK-591, and a failed anti-Alzheimers disease drug, called JNJ-404 as potential candidates. A virtual screen of over 130,000 compounds was also used to help spot candidates. For this, the researchers fed the other screening results into a computer and then used artificial intelligence-based programs to learn what makes a compound good at blocking NS2B-NS3 Zika virus protease activity.
These results show that taking advantage of the latest technological advances can help researchers find treatments that can be repurposed to fight other diseases, said Dr. Simeonov.
The Zika virus is known to preferentially infect stem cells in the brain. Scientists suspect this is the reason why infections cause more harm to newborn babies than to adults. Experiments on neural stem cells grown in petri dishes indicated that all three drugs identified in this study may counteract these problems. Treating the cells with methacycline, MK-591, or JNJ-404 reduced Zika virus infections.
Because tetracyclines are U.S. Food and Drug Administration-approved drugs that are known to cross the placenta of pregnant women, the researchers focused on methacycline and found that it may reduce some neurodevelopmental problems caused by the Zika virus. For instance, Zika-infected newborn mice that were treated with methacycline had better balance and could turn over more easily than ones that were given a placebo. Brain examinations suggested this was because the antibiotic reduced infections and neural damage. Nevertheless, the antibiotics did not completely counteract harm caused by the Zika virus. The weight of mice infected with the virus was lower than control mice regardless of whether the mice were treated with methacycline.
These results suggest that tetracycline-based antibiotics may at least be effective at preventing the neurological problems associated with Zika virus infections, said Dr. Abrams. Given that they are widely used, we hope that we can rapidly test their potential in clinical trials.
Therapeutic Candidates for the Zika Virus Identified by a High Throughput Screen for Zika Protease Inhibitors.PNAS, November 23, 2020
- Winter Weather Impacting Blood and Platelet Donations - Milwaukee Community Journal - February 17th, 2021
- Joshua Shirk continues to fight the odds; mom says God placed people where they needed to be to help him - Keyser Mineral Daily News Tribune - February 17th, 2021
- Evotec and Medical Center Hamburg-Eppendorf Enter Partnership to Develop iPSC-Based Tissue Therapy for Heart Failure - GuruFocus.com - February 7th, 2021
- ProgenCell - Stem Cell Therapies offers an updated Stem Cell Therapy for Anti Aging Protocol - PR Web - January 30th, 2021
- Doctors urge immunocompromised to get COVID vaccine when it becomes available - KMTV - 3 News Now - January 30th, 2021
- Autologous Stem Cell and Non Stem Based therapies Market Share, Size 2021 Global Industry Future Trends, Growth, Strategies,, Segmentation, In-depth... - January 30th, 2021
- Studies Indicating T-Cells May Be Needed For Long-Term Protection From The SARS-Cov-2 Virus - PRNewswire - January 30th, 2021
- Researchers use patients' cells to test gene therapy for rare eye disease - National Institutes of Health - January 30th, 2021
- Two Gene Therapies Fix Fault in Sickle Cell Disease and -thalassemia - MD Magazine - January 30th, 2021
- If I Have Cancer, Dementia or MS, Should I Get the Covid Vaccine? - Kaiser Health News - January 30th, 2021
- L-MIND Trial Results Show CD19 Antibody Is Reasonable in R/R DLBCL - Targeted Oncology - January 30th, 2021
- Profile of T Cells, Broadly Neutralizing Antibodies, Anti-Viral Targets: COVID-19 Updates - Bio-IT World - January 30th, 2021
- HealthLynked's The Future of Healthcare Summit Brings Healthcare Experts and Technology Innovators from Around the World to Naples, Florida - WFMZ... - January 30th, 2021
- Tevogen Bio Secures Funding from Team of Doctors to Support Clinical Trials of Its Investigational Curative T Cell Therapy for COVID-19 - PRNewswire - January 25th, 2021
- Novel Treatment Leads to Dog's Recovery - The Bark - January 25th, 2021
- Identification and Targeting of ThomsenFriedenreich and IL1RAP | OTT - Dove Medical Press - January 25th, 2021
- Regenerative Medicine Market Size Worth $74831.35 Million With CAGR of 22.27% By 2024 | Segmented by Product Type, Top Manufacturers, By End-User... - January 25th, 2021
- Immunotherapy Inches Forward in Development of Myeloid Malignancies - OncLive - January 14th, 2021
- Cytovia Therapeutics Partners with National Cancer Institute to Develop Novel Gene-Edited, iPSC-Derived GPC3 CAR NK Cells for the Treatment of Solid... - January 14th, 2021
- Kaleido Biosciences Announces Positive Interim Results of Controlled Study of KB109 in Patients with Mild-to-Moderate COVID-19 - BioSpace - January 14th, 2021
- Doctors Make Medical Breakthrough In Treating Severe Cases Of COVID - CBS San Francisco - January 9th, 2021
- Mana joins the hectic fight against solid tumors with an 'off-the-shelf' candidate angling for an IND this year - Endpoints News - January 9th, 2021
- Versiti Blood Centers and Noodles & Company Serve Up Thanks to Blood Donors - PRNewswire - December 31st, 2020
- Global CAR-T Pipeline Insight Report 2020: Overview, Landscape, Therapeutic Assessment, Current Treatment Scenario and Emerging Therapies -... - December 31st, 2020
- 2020 health care year in review - Crain's Cleveland Business - December 31st, 2020
- The Top 10 FDA Oncology Drug Approvals of 2020 - Curetoday.com - December 31st, 2020
- Gut microbiota: How does it interact with the brain? - Medical News Today - December 31st, 2020
- Numerous Indian American STEM Researchers Named Fellows of American Association for the Advancement of Sciences - India West - December 31st, 2020
- Four years after devastating spinal injury, former St. Paul's football player reunites with caregivers - NOLA.com - December 24th, 2020
- New Combination Therapy Tested By Children's May Offer Hope For Leukemia Patients - WVXU - December 24th, 2020
- Real-time observation helpful in Stem cell for vascular diseases: Study - Hindustan Times - December 21st, 2020
- NurOwn May Be Given to Early ALS Patients in US Who Finished Phase... - ALS News Today - December 21st, 2020
- Follow the Money: Spatial Omics, CAR-NK Cells, AI-Powered Biology - Bio-IT World - December 21st, 2020
- Explained: Process of transporting stem cell from donor to patient for a successful transplant - Firstpost - December 18th, 2020
- Research That Saves Lives: Four COVID-19 Therapies Being Tested at UVA - University of Virginia - December 18th, 2020
- Even if You've Had COVID-19 You Still Need the Vaccine - Healthline - December 18th, 2020
- What Patients With Cancer, Survivors Need to Know About the Emergency Use Authorization of COVID-19 Vaccine - Curetoday.com - December 16th, 2020
- 2020 at the U: The year in review - University of Miami - December 16th, 2020
- Five Mobile County hospitals to get Pfizer vaccine this week - AL.com - December 16th, 2020
- Donor Stem Cell Transplant Improves Survival in Older Patients with Myelodysplastic Syndrome - Cancer Health Treatment News - December 10th, 2020
- Positive Phase 2 Proof-of-Concept Data for Viralym-M and Burden of Disease Data Presented in Oral Presentations at the 62nd American Society of... - December 10th, 2020
- Dr. Kansagra: Quadruplet Therapy for Newly Diagnosed Multiple Myeloma and Combination CAR T-Cell Opportunities - DocWire News - December 10th, 2020
- Silicon Therapeutics Announces Members of Scientific Advisory Board - Business Wire - December 10th, 2020
- Israeli Neurogenesis' NG-01 slows progressive MS by up to 90% in phase II study - BioWorld Online - December 10th, 2020
- ADC Therapeutics Announces Updated Clinical Data on Lead Antibody Drug Conjugate Programs Loncastuximab Tesirine (Lonca) and Camidanlumab Tesirine... - December 10th, 2020
- Magenta Therapeutics Announces Commencement of First Phase 2 Clinical Trial of MGTA-145 for Stem Cell Mobilization, Oral Presentation of MGTA-145... - December 8th, 2020
- Precigen Presents New Data Supporting the Safety, Clinical Activity, Expansion and Persistence of PRGN-3006 UltraCAR-T at the 62nd ASH Annual Meeting... - December 8th, 2020
- ALLO-715, Off-the-Shelf CAR T-Cell Therapy, Produces Early Promise in Multiple Myeloma - Cancer Network - December 8th, 2020
- Rocket Pharmaceuticals Presents Positive Clinical Data from its Fanconi Anemia and Leukocyte Adhesion Deficiency-I Programs at the 62nd American... - December 8th, 2020
- Negrin Shines Light on the Orca-T Story in GVHD - OncLive - December 8th, 2020
- Preliminary Results from NexImmune's Phase 1/2 Trial of NEXI-001 in AML Presented at 62nd ASH Annual Meeting and Exposition - GlobeNewswire - December 8th, 2020
- BeiGene Announces the Approval in China of BLINCYTO (Blinatumomab) for Injection for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute... - December 8th, 2020
- Sutro Biopharma Presents Data from Ongoing Phase 1 Dose-Escalation Study for STRO-001 for the Treatment of B-cell Non-Hodgkin Lymphoma at the 62nd... - December 8th, 2020
- Data from the ANDROMEDA Study Show Hematologic Response for DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in Newly Diagnosed Light Chain (AL)... - December 8th, 2020
- US FDA Approves Naxitamab for the Treatment of Neuroblastoma - OncoZine - November 29th, 2020
- Coronavirus treatments and vaccines. Here are the latest developments - San Francisco Chronicle - November 29th, 2020
- Dr Apar Kishor Ganti Outlines the Effectiveness of Lurbinectedin and Benefits Over Competition - AJMC.com Managed Markets Network - November 26th, 2020
- Commonly used antibiotic shows promise for combating Zika infections - National Institutes of Health - November 26th, 2020
- A real life Superman celebrates 5 years of survival from one of the deadliest cancers - Newswise - November 26th, 2020
- Global Cell Harvesting Market to Reach US$381,4 Million by the Year 2027 - Salamanca Press - November 26th, 2020
- Tanya Siddiqi, MD, Discusses the Promise of Reduced Toxicity With Liso-Cel - AJMC.com Managed Markets Network - November 26th, 2020
- Study Suggests AYAs Treated for AML Have High Risk of Developing Long-Term Complications - Cancer Network - November 26th, 2020
- Mustang Bio Announces Positive Opinion from the European Medicines Agency on Orphan Drug Designation for Its Lentiviral Gene Therapy for the Treatment... - November 26th, 2020
- Study Finds Racial and Ethnic Disparities in Treatment of AL Amyloidosis - DocWire News - November 22nd, 2020
- New Virtual Reality Tool, Domestic Cats are SARS-CoV-2 Carriers, Combination Therapy Advances: COVID-19 Updates - Bio-IT World - November 22nd, 2020
- SEE | Smoking worsens Covid-19 infection in the airways, new study reveals - Health24 - November 22nd, 2020
- Could Cell Therapy Be The Answer To COVID-19? - CBS Boston - November 3rd, 2020
- CA Prop 14 Explained: What To Know Before You Vote Election Day - Los Angeles, CA Patch - November 3rd, 2020
- GMP Cell Banking Services Market Predicted to Accelerate the Growth by 2019-2029 - TechnoWeekly - November 3rd, 2020
- Making Progress Against Relapsed/ Refractory DLBCL Without CAR T - OncLive - November 3rd, 2020
- Orchard Therapeutics to Host Virtual R&D Investor Event on Friday, November 13, 2020 - GlobeNewswire - November 3rd, 2020
- Editorial Article: Combating cancer: The incubation technology accelerating CAR-T cell therapy development - SelectScience - October 31st, 2020
- Richters Transformation: When a Slow-Growing Cancer Turns Aggressive - SurvivorNet - October 31st, 2020
- Detroit Pistons, Make-A-Wish put a smile on the face of Commerce Township boy - The Oakland Press - October 31st, 2020
- NexImmune Establishes Research Initiative with City of Hope to Focus on Novel Immunotherapeutic Approaches to Acute Myeloid Leukemia - Yahoo Finance - October 31st, 2020
- HBS and Harvard's Department of Stem Cell and Regenerative Biology Receive $25 Million Gift from The Chris and Carrie Shumway Foundation to Support... - October 23rd, 2020
- Harnessing regeneration of retinal tissues: An option almost within reach - Ophthalmology Times - October 23rd, 2020
- Fate Therapeutics' and Celyad's CAR therapies in oncology offer potential - pharmaceutical-technology.com - October 23rd, 2020
- World Wide Stem Cell Treatment Centers Provides Exceptional Regenerative Treatment Options To Those in Need - GlobeNewswire - October 16th, 2020
- Proposition 14: Stem cell research bonds City Times - City Times - October 16th, 2020