scholarly journals Inhibition of SARS-CoV-2 by Targeting Conserved Viral RNA Structures and Sequences

2021 ◽  
Vol 9 ◽  
Author(s):  
Shalakha Hegde ◽  
Zhichao Tang ◽  
Junxing Zhao ◽  
Jingxin Wang
Keyword(s):  
Small Molecules ◽  
Rna Binding ◽  
Antiviral Drug ◽  
Viral Rna ◽  
Rna Structures ◽  
Drug Candidates ◽  
Novel Approach ◽  
Rna Targeting ◽  
New Type ◽  
Chimeric Rna

The ongoing COVID-19/Severe Acute Respiratory Syndrome CoV-2 (SARS-CoV-2) pandemic has become a significant threat to public health and has hugely impacted societies globally. Targeting conserved SARS-CoV-2 RNA structures and sequences essential for viral genome translation is a novel approach to inhibit viral infection and progression. This new pharmacological modality compasses two classes of RNA-targeting molecules: 1) synthetic small molecules that recognize secondary or tertiary RNA structures and 2) antisense oligonucleotides (ASOs) that recognize the RNA primary sequence. These molecules can also serve as a “bait” fragment in RNA degrading chimeras to eliminate the viral RNA genome. This new type of chimeric RNA degrader is recently named ribonuclease targeting chimera or RIBOTAC. This review paper summarizes the sequence conservation in SARS-CoV-2 and the current development of RNA-targeting molecules to combat this virus. These RNA-binding molecules will also serve as an emerging class of antiviral drug candidates that might pivot to address future viral outbreaks.

RNA targeting through binding of small molecules: Studies on t-RNA binding by the cytotoxic protoberberine alkaloidcoralyne

2009 ◽  
Vol 5 (3) ◽  
pp. 244-254 ◽  
Author(s):  
Md. Maidul Islam ◽  
Prateek Pandya ◽  
Surat Kumar ◽  
Gopinatha Suresh Kumar
Keyword(s):  
Small Molecules ◽  
Rna Binding ◽  
Rna Targeting

Targeting Micrornas With Small Molecules: A Novel Approach to Treating Breast Cancer

2010 ◽  
Author(s):  
George A. Calin ◽  
Shuxing Zhang ◽  
Waldemar Priebe
Keyword(s):  
Breast Cancer ◽  
Small Molecules ◽  
Novel Approach

Recent Updates in the Alzheimer’s Disease Etiopathology and Possible Treatment Approaches: A Narrative Review of Current Clinical Trials

2020 ◽  
Vol 13 (4) ◽  
pp. 273-294 ◽  
Author(s):  
Elahe Zarini-Gakiye ◽  
Javad Amini ◽  
Nima Sanadgol ◽  
Gholamhassan Vaezi ◽  
Kazem Parivar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Small Molecules ◽  
Clinical Trial Design ◽  
Treatment Approaches ◽  
Drug Candidates ◽  
Novel Treatments ◽  
Approved Drugs ◽  
Tau Aggregation

Background: Alzheimer’s disease (AD) is the most frequent subtype of incurable neurodegenerative dementias and its etiopathology is still not clearly elucidated. Objective: Outline the ongoing clinical trials (CTs) in the field of AD, in order to find novel master regulators. Methods: We strictly reviewed all scientific reports from Clinicaltrials.gov and PubMed databases from January 2010 to January 2019. The search terms were “Alzheimer's disease” or “dementia” and “medicine” or “drug” or “treatment” and “clinical trials” and “interventions”. Manuscripts that met the objective of this study were included for further evaluations. Results: Drug candidates have been categorized into two main groups including antibodies, peptides or hormones (such as Ponezumab, Interferon β-1a, Solanezumab, Filgrastim, Levemir, Apidra, and Estrogen), and naturally-derived ingredients or small molecules (such as Paracetamol, Ginkgo, Escitalopram, Simvastatin, Cilostazo, and Ritalin-SR). The majority of natural candidates acted as anti-inflammatory or/and anti-oxidant and antibodies exert their actions via increasing amyloid-beta (Aβ) clearance or decreasing Tau aggregation. Among small molecules, most of them that are present in the last phases act as specific antagonists (Suvorexant, Idalopirdine, Intepirdine, Trazodone, Carvedilol, and Risperidone) or agonists (Dextromethorphan, Resveratrol, Brexpiprazole) and frequently ameliorate cognitive dysfunctions. Conclusion: The presences of a small number of candidates in the last phase suggest that a large number of candidates have had an undesirable side effect or were unable to pass essential eligibility for future phases. Among successful treatment approaches, clearance of Aβ, recovery of cognitive deficits, and control of acute neuroinflammation are widely chosen. It is predicted that some FDA-approved drugs, such as Paracetamol, Risperidone, Escitalopram, Simvastatin, Cilostazoand, and Ritalin-SR, could also be used in off-label ways for AD. This review improves our ability to recognize novel treatments for AD and suggests approaches for the clinical trial design for this devastating disease in the near future.

scholarly journals Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

2021 ◽  
Vol 9 (7) ◽  
pp. 1519
Author(s):  
Sonia R. Isaacs ◽  
Dylan B. Foskett ◽  
Anna J. Maxwell ◽  
Emily J. Ward ◽  
Clare L. Faulkner ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Viral Infections ◽  
Antiviral Drug ◽  
Virus Detection ◽  
Detection Methods ◽  
Islet Autoimmunity ◽  
Comprehensive Overview ◽  
Drug Candidates

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, as well as mechanistic studies of virus-infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here, we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

scholarly journals Bioactive Secondary Metabolites of the Genus Diaporthe and Anamorph Phomopsis from Terrestrial and Marine Habitats and Endophytes: 2010–2019

2021 ◽  
Vol 9 (2) ◽  
pp. 217
Author(s):  
Tang-Chang Xu ◽  
Yi-Han Lu ◽  
Jun-Fei Wang ◽  
Zhi-Qiang Song ◽  
Ya-Ge Hou ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Small Molecules ◽  
Host Plants ◽  
Plant Pathogens ◽  
Bioactive Metabolites ◽  
Drug Candidates ◽  
The Past ◽  
Marine Habitats ◽  
Bioactive Secondary Metabolites ◽  
Unidentified Species

The genus Diaporthe and its anamorph Phomopsis are distributed worldwide in many ecosystems. They are regarded as potential sources for producing diverse bioactive metabolites. Most species are attributed to plant pathogens, non-pathogenic endophytes, or saprobes in terrestrial host plants. They colonize in the early parasitic tissue of plants, provide a variety of nutrients in the cycle of parasitism and saprophytism, and participate in the basic metabolic process of plants. In the past ten years, many studies have been focused on the discovery of new species and biological secondary metabolites from this genus. In this review, we summarize a total of 335 bioactive secondary metabolites isolated from 26 known species and various unidentified species of Diaporthe and Phomopsis during 2010–2019. Overall, there are 106 bioactive compounds derived from Diaporthe and 246 from Phomopsis, while 17 compounds are found in both of them. They are classified into polyketides, terpenoids, steroids, macrolides, ten-membered lactones, alkaloids, flavonoids, and fatty acids. Polyketides constitute the main chemical population, accounting for 64%. Meanwhile, their bioactivities mainly involve cytotoxic, antifungal, antibacterial, antiviral, antioxidant, anti-inflammatory, anti-algae, phytotoxic, and enzyme inhibitory activities. Diaporthe and Phomopsis exhibit their potent talents in the discovery of small molecules for drug candidates.

Synthesis of Multi-Substituted Bicycloalkyl Boronates: An Intramolecular Coupling Approach to Alkyl Bioisosteres

2021 ◽  
Author(s):  
Yangyang Yang ◽  
Jet Tsien ◽  
Jonathan Hughes ◽  
Byron Peters ◽  
Rohan Merchant ◽  
...  
Keyword(s):  
Intramolecular Cyclization ◽  
Material Chemistry ◽  
Novel Approach ◽  
Coupling Approach ◽  
New Type ◽  
Strain Release ◽  
Synthetic Studies ◽  
Bicyclic Molecules

<p>Bicyclic hydrocarbons, bicyclo[1.1.1]pentanes (BCPs) in particular, play an emerging role as saturated bioisosteres in pharmaceutical, agrochemical, and material chemistry. Taking advantage of strain release strategies, prior synthetic studies have featured the synthesis of bridgehead-substituted (C1, C3) BCPs from [1.1.1]propellane. This work describes a novel approach to accessing multi-substituted BCPs via a new type of intramolecular cyclization. In addition to the C1, C3-disubstituted BCPs, this method also enables the construction of yet underexplored tri-substituted (C1, C2 and C3) BCPs from readily accessible cyclobutanones. The broad generality of this cyclization is examined through synthesis of a variety of caged bicyclic molecules, ranging from [1.1.1] to [3.2.1] scaffolds. The modularity afforded by the pendant bridgehead Bpin resulted from the cyclization is demonstrated via several downstream functionalizations, highlighting the ability of this approach for programmed and divergent synthesis of multi-substituted bicyclic hydrocarbons.<br></p>

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