Research Briefing |
Featured
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Article |
Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity
New agonists of the serotonin 5-HT2A receptor (5-HT2AR) confer high brain permeability and antidepressant activity and—in contrast to classic 5-HT2AR agonists—lack psychedelic activity.
- Anat Levit Kaplan
- , Danielle N. Confair
- & Jonathan A. Ellman
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Article |
Methotrexate recognition by the human reduced folate carrier SLC19A1
Cryo-EM structures provide insight into how the antifolate methotrexate, a chemotherapy drug, is recognized by the reduced folate carrier.
- Nicholas J. Wright
- , Justin G. Fedor
- & Seok-Yong Lee
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News |
Billion-dollar project aims to prep drugs before the next pandemic
A centre in Australia, set up with a Aus$250-million donation, will focus on creating therapies for future infectious-disease outbreaks.
- Felicity Nelson
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Clinical Briefing |
Non-viral, precisely engineered immune cells tested in lymphoma
An improved approach has been developed for producing precisely designed immune cells called CAR T cells that recognize and kill cancer cells. CAR T cells generated in this way were safe and showed potential therapeutic effects in individuals with a relapsed or treatment-resistant form of the immune-cell cancer called B-cell non-Hodgkin’s lymphoma.
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News Round-Up |
Memory boost, forever chemicals and dark-matter signal
The latest science news, in brief.
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Article
| Open AccessNon-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL
Non-viral CAR-T cells with gene-specific targeted integration are safe and effective in patients with lymphoma.
- Jiqin Zhang
- , Yongxian Hu
- & He Huang
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News Explainer |
Can a smallpox drug treat monkeypox? Here’s what scientists know
Tecovirimat, a little-known antiviral, shows promise against monkeypox. But human data and supplies of the drug are limited.
- Max Kozlov
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Outlook |
Psychedelic drugs take on depression
Mind-altering drugs might provide relief for those who don’t respond to conventional therapies — but does the hype outweigh the hope?
- Cassandra Willyard
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Nature Podcast |
How to make water that’s full of holes
Embedded ‘nanocages’ help water dissolve large amounts of gas, and potential evidence that hominins walked on two legs seven million years ago.
- Benjamin Thompson
- & Shamini Bundell
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News |
How to destroy ‘forever chemicals’: cheap method breaks down PFAS
Disposing of these persistent substances often requires high pressures and temperatures.
- Giorgia Guglielmi
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News Feature |
Long-COVID treatments: why the world is still waiting
After a slow start, researchers are beginning to test ways to combat the lasting symptoms of the disease.
- Heidi Ledford
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Article |
Inhibition of ASGR1 decreases lipid levels by promoting cholesterol excretion
Inhibiting the asialoglycoprotein receptor ASGR1 increases cholesterol excretion to the bile and then faeces, providing a unique way to lower cholesterol, and therefore providing a safe and effective way to treat cardiovascular disease.
- Ju-Qiong Wang
- , Liang-Liang Li
- & Bao-Liang Song
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News |
China approves first homegrown COVID antiviral
The country’s drug regulator has granted conditional authorization for an HIV drug to be used to treat COVID-19.
- Yvaine Ye
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Article |
Mechanisms and inhibition of Porcupine-mediated Wnt acylation
Cryo-electron microscopy structures of human Porcupine in complex with palmitoleoyl-coenzyme A, the inhibitor LGK974 and its peptide substrate suggest a mechanism for Wnt acylation.
- Yang Liu
- , Xiaofeng Qi
- & Xiaochun Li
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News |
Major wildlife report struggles to tally humanity’s exploitation of species
People use roughly 50,000 plants and animals for food and income, but scientists say the estimate is conservative.
- Smriti Mallapaty
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News Feature |
COVID antibody drugs have saved lives — so why aren’t they more popular?
Drugs made from antibodies are huge money-makers for some conditions — but they have gained little traction in infectious diseases, including COVID.
- Asher Mullard
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Article
| Open AccessStructural basis for SHOC2 modulation of RAS signalling
Cryo-electron microscopy structure, molecular dynamics and biochemical analyses of the SHOC2–PP1C–MRAS complex demonstrate the dependence of the complex formation on RAS–GTP and identify the determinants of RAS isoform preference for SHOC2–PP1C and specificity of the complex for RAF dephosphorylation.
- Nicholas P. D. Liau
- , Matthew C. Johnson
- & Jawahar Sudhamsu
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Technology Feature |
Cloud labs: where robots do the research
A host of companies provide a remote, automated workforce for conducting experiments around the clock.
- Carrie Arnold
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News |
New COVID drugs face delays as trials grow more difficult
Fewer people are eligible for the massive studies needed to test treatments for severe COVID-19.
- Saima May Sidik
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Technology Feature |
How engineers and drug developers are working to change childhood cancer’s deadly calculus
A non-profit organization merges engineering and biology to accelerate drug development for childhood cancers.
- Esther Landhuis
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Article
| Open AccessStructural insights into the HBV receptor and bile acid transporter NTCP
Cryo-electron structures of the hepatitis B virus receptor NTCP show a distinct membrane topology compared with other SLC10 proteins, but a common bile acid transport mechanism that is shared with related mammalian and bacterial proteins.
- Jae-Hyun Park
- , Masashi Iwamoto
- & Sam-Yong Park
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Book Review |
Rise of drug-resistant tuberculosis is hidden in plain sight
A history of TB infections homes in on India to illuminate the racism that denies treatment to millions around the world.
- Heidi Ledford
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Article |
Synthesis and target annotation of the alkaloid GB18
A synthetic route to GB18, an alkaloid from the bark of hallucinogenic Galbulimima sp., is developed, enabling its identification as an antagonist of κ- and μ-opioid receptors.
- Stone Woo
- & Ryan A. Shenvi
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Technology Feature |
Methods combine to decode the biology of tuberculosis
Scientists are fusing sequencing, chemistry and imaging techniques to probe interactions between pathogens and their host cells.
- Amber Dance
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Article
| Open AccessCCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition
Genome-scale CRISPR–Cas9-based synthetic lethality screens identify PKMYT1 as a potential therapeutic target in tumours with CCNE1 amplification.
- David Gallo
- , Jordan T. F. Young
- & Daniel Durocher
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News Feature |
What's next for AlphaFold and the AI protein-folding revolution
DeepMind software that can predict the 3D shape of proteins is already changing biology.
- Ewen Callaway
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Outlook |
Developing a cure for chronic hepatitis B requires a fresh approach
The prevailing dogma for drug development is insufficient; it’s time to recentre efforts around the immune system.
- Matteo Iannacone
- & Luca G. Guidotti
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Outlook |
Closing in on a cure for hepatitis B
Finite courses of treatment could get the virus under control — with the right combination of drugs.
- Elie Dolgin
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Outlook |
Facing the challenge of eliminating hepatitis B
Public-health expert Corinna Dan charts a course to free the United States from the virus.
- Eric Bender
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Article |
Targeting Xist with compounds that disrupt RNA structure and X inactivation
A molecule identified in a screen for compounds that bind the non-coding mouse RNA Xist blocks Xist-dependent X-chromosome inactivation, demonstrating the utility of this approach for identifying drugs that target RNA.
- Rodrigo Aguilar
- , Kerrie B. Spencer
- & Jeannie T. Lee
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Article
| Open AccessA TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic
A small-molecule inhibitor of TMPRSS2 is effective against SARS-CoV-2 variants of concern in human lung cells and in donor-derived colonoids, and also shows prophylactic and therapeutic benefits in a mouse model of COVID-19.
- Tirosh Shapira
- , I. Abrrey Monreal
- & François Jean
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Nature Podcast |
The coin toss of Alzheimer's inheritance
Marty Reiswig talks about his experience in a clinical trial that hopes to delay the onset of Alzheimer's symptoms.
- Lorna Stewart
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News & Views |
Promising reversible protein inhibitors kept on target
Compounds that form reversible covalent bonds with lysine amino-acid residues in proteins have high potential for drug discovery. A chemical group has been reported that prolongs the time for which such compounds bind to their targets.
- Stephan M. Hacker
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News Feature |
Could drugs prevent Alzheimer’s? These trials aim to find out
Researchers are giving drugs to healthy people in hope of clearing away toxic proteins in the brain and warding off neurodegeneration.
- Alison Abbott
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News Feature |
Hundreds of COVID trials could provide a deluge of new drugs
Two years into the pandemic, the COVID-19 drugs pipeline is primed to pump out novel treatments — and fresh uses for familiar therapies.
- Heidi Ledford
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Article
| Open AccessEffective drug combinations in breast, colon and pancreatic cancer cells
A survey of potency and efficacy of 2,025 clinically relevant two-drug combinations against 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines identifies rare synergistic effects of anticancer drugs, informing rational combination treatments for specific cancer subtypes.
- Patricia Jaaks
- , Elizabeth A. Coker
- & Mathew J. Garnett
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Article |
Pyrimidine inhibitors synergize with nucleoside analogues to block SARS-CoV-2
A combination of pyrimidine biosynthesis inhibitors and antiviral nucleoside analogues can boost the antiviral effect of nucleoside analogues against SARS-CoV-2.
- David C. Schultz
- , Robert M. Johnson
- & Sara Cherry
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Career Column |
Why I wrote an impact CV
It’s not easy to demonstrate research impact, says Katherine Andrews — even when there’s a clear clinical need, as in malaria drug development.
- Katherine Andrews
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News |
Why scientists are racing to develop more COVID antivirals
The first crop of antivirals against SARS-CoV-2 is promising. But new drugs will be needed to counter the looming threat of resistance.
- Max Kozlov
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Outlook |
The biological clean-ups that could combat age-related disease
Could targeting autophagy — often likened to a cellular trash management system — extend life? Some researchers are unconvinced.
- Elie Dolgin
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News & Views |
A virtual drug-screening approach to conquer huge chemical libraries
A computational method has been devised to identify drug-candidate molecules from a library of billions of molecules using 100 times less computational power than is used by standard methods.
- Charlotte Deane
- & Maranga Mokaya
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Article |
Synthon-based ligand discovery in virtual libraries of over 11 billion compounds
V-SYNTHES, a scalable and computationally cost-effective synthon-based approach to compound screening, identified compounds with a high affinity for CB2 and CB1 in a hierarchical structure-based screen of more than 11 billion compounds.
- Arman A. Sadybekov
- , Anastasiia V. Sadybekov
- & Vsevolod Katritch
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News |
Merck’s COVID pill loses its lustre: what that means for the pandemic
Molnupiravir was initially heralded by public-health officials as a game-changer for COVID-19, but full clinical-trial data showed lower-than-expected efficacy.
- Max Kozlov
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News |
Half of top cancer studies fail high-profile reproducibility effort
Barriers to reproducing preclinical results included unhelpful author communication, but critics argue that one-time replication attempts don’t tell the whole story.
- Asher Mullard
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Article |
Structures of the σ2 receptor enable docking for bioactive ligand discovery
Crystal structures of the σ2 receptor are determined and used to perform a docking screen of nearly 500 million molecules, identifying σ2-selective ligands and providing insight into the role of σ2 in neuropathic pain.
- Assaf Alon
- , Jiankun Lyu
- & Andrew C. Kruse
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Article |
Structural basis of inhibition of the human SGLT2–MAP17 glucose transporter
Using cryogenic electron microscopy, the structure of the human SGLT2–MAP17 complex captured in the empagliflozin-bound state reveals the inhibitory mechanism of these anti-diabetic drugs.
- Yange Niu
- , Rui Liu
- & Lei Chen
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Article |
Structural basis for ligand reception by anaplastic lymphoma kinase
Analysis of crystal structures of anaplastic lymphoma kinase elucidate the mechanism by which ligand binding and the glycine-rich domain regulate its activity.
- Tongqing Li
- , Steven E. Stayrook
- & Daryl E. Klein