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Trending Papers in drug discovery

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An Alpaca antibody can be used to neutralize SARS-CoV-2 and prevent its entry into target host cells
From Paper: An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
Published: Sep 2020
  • In addition to neutralization activity, we show that Ty1 can be used as a detection reagent in flow cytometry and immunofluorescence demonstrating its suitability as a research tool and for diagnostics
  • Ty1 was identified by binding assay after two consecutive rounds of phage display, simultaneously monitoring sequence enrichment by next generation sequencing
Submitted by Patrick Joyce
9
Horses exhibit a strong neutralizing antibody response when exposed to isolated SARS-CoV-2 S protein
From Paper: Equine hyperimmune globulin raised against the SARS-CoV-2 spike glycoprotein has extremely high neutralizing titers
Authors:
Cunha, Luis Eduardo R., et al
Published: Aug 2020
  • The results show the perspective of using hyperimmune anti-SARS-CoV-2 F(ab')2 preparations as a passive immunization therapy in humans, similar to therapies that have been safely used for decades against rabies, tetanus and snake venoms
  • This study demonstrated that hyperimmune globulin preparations raised in horses against the recombinant trimeric spike (S) glycoprotein of SARS-CoV-2 in the prefusion conformation provide very high ELISA titers as well as highly potent neutralizing activity against SARS-CoV-2
Submitted by Patrick Joyce
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8
A novel gene therapy approach eliminates at least 90% latent herpes simplex virus 1
From Paper: Gene editing and elimination of latent herpes simplex virus in vivo
Author:
Keith R. Jerome
  • The results provide critical insights for the optimization of in vivo gene therapy against HSV, and suggest that meganuclease-mediated gene editing represents a plausible pathway toward HSV cure
  • This study evaluated the gene-editing of Herpes simplex virus (HSV) in a well-established mouse model, using adeno-associated virus (AAV)-delivered meganucleases, as a potentially curative approach to treat latent HSV infection
Submitted by Patrick Joyce
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A SARS-CoV-2 vaccine containing many synthetic copies of the Spike protein receptor-binding domain (RBD) can elicit neutralizing antibodies in rodent and nonhuman primates
  • The authors believe that the protein nanoparticle design of this vaccine will be highly scalable
  • The vaccine contains 60 copies of the SARS-CoV-2 receptor-binding domain (RBD) which elicit a robust immune response in mice and non-human primates
Submitted by Patrick Joyce
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7
An inactivated SARS-CoV-2 vaccine is able to safely produce antibodies within 97%+ of recipients after 28 days
From Paper: Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial
  • The results support the conduction of phase 3 trial for CoronaVac with optimum schedule/dosage per different scenarios.
  • CoronaVac was well tolerated, and no dose-related safety concerns were observed.
Submitted by Patrick Joyce
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5
An association between antidepressant use and reduced morbidity and mortality from COVID-19
From Paper: Association between SSRI Antidepressant Use and Reduced Risk of Intubation or Death in Hospitalized Patients with Coronavirus Disease 2019: a Multicenter Retrospective Observational Study
  • Specifically, exposures to escitalopram, fluoxetine, and venlafaxine were significantly associated with lower risk of intubation or death (all p<0.05)
  • SSRI use could be associated with lower risk of death or intubation in hospitalized patients with COVID-19
Submitted by Patrick Joyce
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3
First-in-Human Trial of a SARS CoV 2 Recombinant Spike Protein Nanoparticle Vaccine
Background NVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins. We present the Day 35 primary analysis of our trial of NVX-CoV2373 with or without the saponin-based Matrix-M1 adjuvant in healthy adults. Methods This is a randomized, observer-blinded, placebo-controlled, phase 1 trial in 131 healthy adults. Trial vaccination comprised two intramuscular injections, 21 days apart. Primary outcomes were reactogenicity, safety labs, and immunoglobulin G (IgG) anti-spike protein response. Secondary outcomes included adverse events, wild-type virus neutralizing antibody, and T-cell responses. Results Participants received NVX-CoV2373 with or without Matrix-M1 (n=106) or placebo (n=25). There were no serious adverse events. Reactogenicity was mainly mild in severity and of short duration (mean ≥ 2 days), with second vaccinations inducing greater local and systemic reactogenicity. The adjuvant significantly enhanced immune responses and was antigen dose-sparing, and the two-dose 5μg NVX-CoV2373/Matrix-M1 vaccine induced mean anti-spike IgG and neutralizing antibody responses that exceeded the mean responses in convalescent sera from COVID-19 patients with clinically significant illnesses. The vaccine also induced antigen-specific T cells with a largely T helper 1 (Th1) phenotype. Conclusions NVX-CoV2373/Matrix-M1 was well tolerated and elicited robust immune responses (IgG and neutralization) four-fold higher than the mean observed in COVID-19 convalescent serum from participants with clinical symptoms requiring medical care and induced CD4+ T-cell responses biased toward a Th1 phenotype. These findings suggest that the vaccine may confer protection and support transition to efficacy evaluations to test this hypothesis. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988).
Submitted by Patrick Joyce
19
A novel method can detect the levels of both plant based and natural cannabinoids in various tissue types. This allows scientists to observe how different strains of Cannabis exert different effects by causing unique tissue-specific changes within the endocannabinoid system
From Paper: Cannabinoidomics – An analytical approach to understand the effect of medical Cannabis treatment on the endocannabinoid metabolome
Published: Jul 2020
  • The results demonstrate that variations in the minor phytocannabinoid contents of the different extracts may lead to varied effects on endocannabinoid concentrations, and on the CBD metabolite profile in the peripheral and central systems
  • The power of this analytical method is demonstrated by analysis of serum and four different sections of mouse brains challenged with three different cannabidiol (CBD)-rich extracts.
Submitted by Patrick Joyce
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97
A group of Harvard geneticists created a DIY COVID-19 vaccine, and are self-administering the formulation to avoid FDA regulations on vaccine production
From Paper: SARS-CoV-2 (2019-nCoV) vaccine
  • The vaccine is suggested to be administered intranasally over a minimum of three separate occasions with 2-3 weeks in between each dose
  • The vaccine consists of five ingredients, which the recipient mixes themselves: 1.) Synthetic SARS-CoV-2 peptides 2.)Chitosan 3.) Sodium tri-phosphate 4.) Sodium Chloride 5.)Deionized water
Submitted by Patrick Joyce
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1
Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB1, CB2 and CB1/CB2 heteromer receptors
BackgroundRecent approved medicines whose active principles are Δ9Tetrahidrocannabinol (Δ9-THC) and/or cannabidiol (CBD) open novel perspectives for other phytocannabinoids also present in Cannabis sativa L. varieties. Furthermore, solid data on the potential benefits of acidic and varinic phytocannabinoids in a variety of diseases are already available. Mode of action of cannabigerol (CBG), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabidivarin (CBDV) and cannabigerivarin (CBGV) is, to the very least, partial.Hypothesis/PurposeCannabinoid CB1 or CB2 receptors, which belong to the G-protein-coupled receptor (GPCR) family, are important mediators of the action of those cannabinoids. Pure CBG, CBDA, CBGA, CBDV and CBGV from Cannabis sativa L. are differentially acting on CB1 or CB2 cannabinoid receptors.Study DesignDetermination of the affinity of phytocannabinoids for cannabinoid receptors and functional assessment of effects promoted by these compounds when interacting with cannabinoid receptors.MethodsA heterologous system expressing the human versions of CB1 and/or CB2 receptors was used. Binding to membranes was measured using radioligands and binding to living cells using a homogenous time resolved fluorescence resonance energy transfer (HTRF) assay. Four different functional outputs were assayed: determination of cAMP levels and of extracellular-signal-related-kinase phosphorylation, label-free dynamic mass redistribution (DMR) and ß-arrestin recruitment.ResultsAffinity of cannabinoids depend on the ligand of reference and may be different in membranes and in living cells. All tested phytocannabinoids have agonist-like behavior but behaved as inverse-agonists in the presence of selective receptor agonists. CBGV displayed enhanced potency in many of the functional outputs. However, the most interesting result was a biased signaling that correlated with differential affinity, i.e. the overall results suggest that the binding mode of each ligand leads to specific receptor conformations underlying biased signaling outputs.ConclusionResults here reported and the recent elucidation of the three-dimensional structure of CB1 and CB2 receptors help understanding the mechanism of action that might be protective and the molecular drug-receptor interactions underlying biased signaling.
Submitted by Patrick Joyce
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