COVID-19 Drug Discovery and Development Why Diverse Strategies Are Critical – Technology Networks
By daniellenierenberg
There is no silver bullet at the moment, and there might never be, said World Health Organization Director-General Tedros Adhanom at a virtual press conference at the beginning of August. While it was this bleak sound bite that made the headlines, Tedros also had words of praise for the progress made towards identifying treatments that aid the recovery of COVID-19 patients with the most serious forms of the disease.Research towards treatments for COVID-19 has been developing at a phenomenal speed, even though it feels as though solutions cant come soon enough; the widespread transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had significant health, economic and social impacts across the globe, and as of September 8th more than 27 million cases and 890,000 deaths have been recorded in 188 countries.
Research groups across the world have set about identifying drugs for the treatment of COVID-19, by screening both novel and existing drugs for their ability to alleviate symptoms and stem viral replication. Here, we provide an update on ongoing global efforts to develop and test drugs for the treatment of COVID-19 and explore the range of strategies being employed.
COVID-19 is a disease which can leave you with anything between a mild sniffle to an unpleasant combination of high fever, heavy fatigue, and lung inflammation and damage. The drivers of clinical symptoms can be roughly divided into two categories: the virus itself and the hyperinflammatory response to the virus that occurs in the most severely ill people. Consequently, efforts to identify appropriate treatments are often focused on one category, and sometimes, a particular patient group or stage of disease. Given the nature of COVID-19, it is highly likely that a combination of drugs (drug cocktail) will be needed to both neutralize the virus and suppress the symptoms of COVID-19. Antiviral treatments may target viral components directly, or other cellular processes involved in viral infection or replication. To date, interventional studies for COVID-19 have attempted to achieve a wide range of goals, including:
Addressing the threat of new and potentially life-threatening pathogens requires deep understanding and accurate, reproducible techniques for developing better tests, vaccines, and treatments. Agilent provides the complete breadth of systems, consumables, software, services, and knowledge you need to support your success.
Sponsored Content
Meet the scientists on the frontline with coronavirus. Video credit: Sanford Burnham Prebys Medical Discovery Institute
Of the ~12,000 compounds screened, 100 inhibited SARS-CoV-2 replication in mammalian cells, 21 of which did so in a dose-response fashion. Achieving a sufficiently high dose concentration to elicit antiviral effects in vivo was predicted to be practical and possible for 13 of these compounds based on EC50 values in various cell lines. The most potent of these were evaluated for antiviral activity in human induced pluripotent stems cell (iPSC)-derived pneumocyte-like cells (five candidates) and in an ex vivo lung culture system (one candidate). The latter candidate is called apilimod, a small molecule inhibitor of an enzyme (phosphoinositide 5-kinase or PIKfyve, an endosomal lipid kinase) important to the endocytic pathway in which SARS-CoV-2 travels along during its journey through the cell. Encouragingly, apilimod potently antagonized viral replication in these tissues, and the findings are in agreement with those of another research group. This month, Kang et al. published an article in PNAS, describing the potent inhibition of SARS-CoV-2 by apilimod, providing further evidence to suggest PIKfyve-inhibition as a potential strategy that could limit infection and disease pathogenesis. The authors also noted that apilimod has passed safety tests in previous clinical trials for nonviral indications.
Chanda highlights the incredible pace at which this work was produced. Typically, a project like this would take years, rather than months. He points out that by wanting to do something quickly, there were sacrifices (and not just weekends). For example, they ran with the assay and the cell lines that allowed them to produce results quickly. This is the reason we put the entire dataset out there not one/three/20 molecules, we put all 100 molecules out there. These are the ones we found because of our experimental system, but please keep testing the others because youll probably find other things that work, said Chanda.
To design multiple peptide sequences that can competitively bind to the SARS-CoV-2 receptor binding domain, the University of Michigan research group used a protein design system called EvoDesign.EvoDesign is the first de novo protein design protocol developed in our lab; it performs design simulation by combining the evolution-based information collected from protein databases and an accurate physics- and knowledge-based energy function, namely EvoEF2, for computing atomic interactions such as van der Waals forces, electrostatics, hydrogen bonding, and desolvation energies, said Huang.
Overall, these sophisticated computational tools represent a promising new avenue for the de novo development of drug discovery studies.
Read more:
COVID-19 Drug Discovery and Development Why Diverse Strategies Are Critical - Technology Networks
- Developing the Cell-Based Therapies of the Future - University of Miami - November 15th, 2024
- Advancing heart stem cell therapy - UHN Foundation - November 15th, 2024
- Heart defects affect 40,000 US babies every year but cutting edge AI and stem cell tech will save lives and even cure them in the womb - New York... - November 15th, 2024
- Science Is Finding Ways to Regenerate Your Heart - The Wall Street Journal - November 6th, 2024
- AIIMS Bathinda Makes Breakthrough in Stem Cell Therapy Research for Heart Ailments - Elets - October 21st, 2024
- USC launches collaboration with StemCardia to advance heart regeneration therapies - University of Southern California - October 13th, 2024
- The heart is a resident tissue for hematopoietic stem and progenitor cells in zebrafish - Nature.com - September 3rd, 2024
- Opthea Announces Results of the A$55.9m (US$36.9m¹) Retail Entitlement Offer - July 16th, 2024
- Benitec Biopharma Reports Continued Durable Improvements in the Radiographic Assessments of Swallowing Efficiency and the Subject-Reported Outcome... - July 16th, 2024
- AstraZeneca Closes Acquisition of Amolyt Pharma - July 16th, 2024
- Addex Presents Positive Results from GABAB PAM Cough Program at the Thirteenth London International Cough Symposium (13th LICS) - July 16th, 2024
- Lexeo Therapeutics Announces Positive Interim Phase 1/2 Clinical Data of LX2006 for the Treatment of Friedreich Ataxia Cardiomyopathy - July 16th, 2024
- ANI Pharmaceuticals Announces the FDA Approval and Launch of L-Glutamine Oral Powder - July 16th, 2024
- MediWound Announces $25 Million Strategic Private Placement Financing - July 16th, 2024
- Atsena Therapeutics Appoints Joseph S. Zakrzewski as Board Chair - July 16th, 2024
- ASLAN Pharmaceuticals Announces Receipt of Nasdaq Delisting Determination; Has Determined Not to Appeal - July 16th, 2024
- Kraig Biocraft Laboratories Completes Phase One of its Spider Silk Production Facility Expansion - July 16th, 2024
- Pliant Therapeutics Announces Positive Long-Term Data from the INTEGRIS-PSC Phase 2a Trial Demonstrating Bexotegrast was Well Tolerated at 320 mg with... - July 16th, 2024
- Oncternal Announces Enrollment Completed and Dosing Initiated for Sixth Dose Cohort of Phase 1/2 Study of ONCT-534 for the Treatment of R/R Metastatic... - July 16th, 2024
- Rectify Pharmaceuticals Appoints Bharat Reddy as Chief Business Officer - July 16th, 2024
- Spectral AI Continues Support of Naked Short Selling Inquiry - July 16th, 2024
- Milestone Pharmaceuticals Refreshes Board of Directors - July 16th, 2024
- New Published Data Highlights Potential Cost-Savings of INPEFA® (sotagliflozin) for Heart Failure - July 16th, 2024
- Regenerative medicine can be a boon for those with Drug-Resistant Tuberculosis - Hindustan Times - April 21st, 2023
- Cardiac stem cells: Current knowledge and future prospects - April 13th, 2023
- Stem cell therapies in cardiac diseases: Current status and future ... - April 13th, 2023
- Stem Cell and Regenerative Biology | Johns Hopkins Heart and Vascular ... - April 13th, 2023
- Center for Regenerative Biotherapeutics - Cardiac Regeneration - April 13th, 2023
- MAGENTA THERAPEUTICS, INC. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com - March 25th, 2023
- CAREDX, INC. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com - March 1st, 2023
- A Possible Connection between Mild Allergic Airway Responses and Cardiovascular Risk Featured in Toxicological Sciences - Newswise - February 4th, 2023
- Baby's life saved by surgeon who carried out world's first surgery ... - December 25th, 2022
- An organoid model of colorectal circulating tumor cells with stem cell ... - December 25th, 2022
- Skeletal Muscle Cell Induction from Pluripotent Stem Cells - December 1st, 2022
- Stem-cell niche - Wikipedia - December 1st, 2022
- Scientists Discover Protein Partners that Could Heal Heart Muscle | Newsroom - UNC Health and UNC School of Medicine - October 13th, 2022
- Global Induced Pluripotent Stem Cell ((iPSC) Market to Reach $0 Thousand by 2027 - Yahoo Finance - October 13th, 2022
- Scientists Spliced Human Brain Tissue Into The Brains of Baby Rats - ScienceAlert - October 13th, 2022
- Decoding the transcriptome of calcified atherosclerotic plaque at single-cell resolution | Communications Biology - Nature.com - October 13th, 2022
- Global Synthetic Stem Cells Market Is Expected To Reach Around USD 42 Million By 2025 - openPR - October 13th, 2022
- Merck and Moderna Announce Exercise of Option by Merck for Joint Development and Commercialization of Investigational Personalized Cancer Vaccine -... - October 13th, 2022
- Regenerative Medicine For Heart Diseases: How It Is Better Than Conventional Treatments | TheHealthSite.co - TheHealthSite - October 5th, 2022
- 'Love hormone' oxytocin could help reverse damage from heart attacks via cell regeneration - Study Finds - October 5th, 2022
- Recapitulating Inflammation: How to Use the Colon Intestine-Chip to Study Complex Mechanisms of IBD - Pharmaceutical Executive - September 27th, 2022
- Adult Stem Cells // Center for Stem Cells and Regenerative Medicine ... - September 19th, 2022
- CCL7 as a novel inflammatory mediator in cardiovascular disease, diabetes mellitus, and kidney disease - Cardiovascular Diabetology - Cardiovascular... - September 19th, 2022
- Kite's CAR T-cell Therapy Yescarta First in Europe to Receive Positive CHMP Opinion for Use in Second-line Diffuse Large B-cell Lymphoma and... - September 19th, 2022
- Neural crest - Wikipedia - September 3rd, 2022
- Rise In Number Of CROS In Various Regions Such As Europe Is Expected To Fuel The Growth Of Induced Pluripotent Stem Cell Market At An Impressive CAGR... - September 3rd, 2022
- Discover the Mental and Physical Health Benefits of Fasting - Intelligent Living - September 3rd, 2022
- Heart Association fellowship to support research - Binghamton - August 26th, 2022
- Repeated intravenous administration of hiPSC-MSCs enhance the efficacy of cell-based therapy in tissue regeneration | Communications Biology -... - August 26th, 2022
- High intensity interval training protects the heart against acute myocardial infarction through SDF-1a, CXCR4 receptors and c-kit levels - Newswise - August 26th, 2022
- Yale University: Uncovering New Approaches to a Common Inherited Heart Disorder | India Education - India Education Diary - August 10th, 2022
- Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery | International Journal of Obesity -... - August 10th, 2022
- Pigs died after heart attacks. Scientists brought their cells back to life. - Popular Science - August 10th, 2022
- Protocol for a Nested, Retrospective Study of the Australian Placental Transfusion Study Cohort - Cureus - August 10th, 2022
- Autologous Cell Therapy Market Size to Grow by USD 4.11 billion, Bayer AG and Brainstorm Cell Therapeutics Inc. Among Key Vendors - Technavio - PR... - August 2nd, 2022
- UTSW researcher part of team awarded $36 million heart research grant - The Dallas Morning News - August 2nd, 2022
- Buffalo center fuels research that can save your life from heart disease and stroke - Buffalo News - August 2nd, 2022
- Hyperglycaemia-Induced Impairment of the Autorhythmicity and Gap Junction Activity of Mouse Embryonic Stem Cell-Derived Cardiomyocyte-Like Cells -... - July 25th, 2022
- NASA's Solution to Stem Cell Production is Out of this World - BioSpace - July 25th, 2022
- Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor | Signal Transduction and Targeted Therapy - Nature.com - July 25th, 2022
- 'My Teen Sweetheart And I Drifted Apart. 30 Years Later I Made a Shocking Discovery' - Newsweek - July 25th, 2022
- EU: New Blood? Proposed Revisions to the EUs Blood, Tissues and Cells Rules - GlobalComplianceNews - July 25th, 2022
- Stem Cells Market to Expand at a CAGR of 10.4% from 2021 to 2028 Travel Adventure Cinema - Travel Adventure Cinema - July 25th, 2022
- Cell Separation Technologies Market Expands with Rise in Prevalence of Chronic Diseases, States TMR Study - GlobeNewswire - July 25th, 2022
- Dental Membrane and Bone Graft Substitutes Market to Exceed Value of US$ 1,337 Mn by 2031 - PR Newswire UK - July 25th, 2022
- Stem Cells Used to Repair Heart Defects in Children - NBC 5 Dallas-Fort Worth - July 16th, 2022
- Pneumonia and Heart Disease: What You Should Know - Healthline - July 16th, 2022
- Promising solution to fatal genetic-disorder complications discovered by University professor and Ph.D. candidate - Nevada Today - July 16th, 2022
- Current and advanced therapies for chronic wound infection - The Pharmaceutical Journal - July 16th, 2022
- Why do some women struggle to breastfeed? A UCSC researcher on what we know, and don't - Lookout Santa Cruz - July 16th, 2022
- Mesenchymal stem cells: from roots to boost - PMC - July 8th, 2022
- New study allows researchers to more efficiently form human heart cells from stem cells - University of Wisconsin-Madison - July 8th, 2022
- Dr Victor Chang saved hundreds of lives. 31 years ago today, he was murdered. - Mamamia - July 8th, 2022
- Exosome Therapeutics Market Research Report Size, Share, New Trends and Opportunity, Competitive Analysis and Future Forecast Designer Women -... - July 8th, 2022
- Cell Line Development Market: Increase in Prevalence of Cancer and Other Chronic Diseases to Drive the Market - BioSpace - July 8th, 2022
- Homology Medicines Announces Peer-Reviewed Publication on Novel Discovery of AAVHSC with Robust Distribution to the Central Nervous System and... - July 8th, 2022
- What New Advances are there in 3D Bioprinting Tissues? - AZoM - June 30th, 2022