Related Experiment Video
Updated: Sep 4, 2025
10:29
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
1.5K
The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants
Sylvia Rothenberger1,2, Daniel L Hurdiss3,4, Marcel Walser5
1Spiez Laboratory, Austrasse, Spiez, Switzerland.
Nature Biotechnology
|July 21, 2022
Summary
Ensovibep, a novel therapeutic, effectively neutralizes SARS-CoV-2 variants by targeting the spike protein. This designed ankyrin repeat protein (DARPin) shows promise as a broad-spectrum treatment for COVID-19, reducing fatalities and viral escape mutations.
Area of Science:
- Virology
- Drug Discovery
- Structural Biology
Background:
- Emerging SARS-CoV-2 variants pose a significant threat due to potential drug resistance.
- Development of novel therapeutics with broad variant activity is crucial for managing COVID-19.
Purpose of the Study:
- To evaluate ensovibep, a trispecific DARPin, as a potential therapeutic agent against SARS-CoV-2 variants.
- To investigate the mechanism of action and efficacy of ensovibep in vitro and in vivo.
Main Methods:
- Cryo-electron microscopy was used to analyze the binding of ensovibep to the SARS-CoV-2 spike protein trimer.
- In vitro viral passaging experiments were conducted to assess the emergence of escape mutations.
- Roborovski dwarf hamsters were infected with SARS-CoV-2 to evaluate ensovibep's efficacy in reducing fatality.
Main Results:
- Ensovibep demonstrated high-potency inhibition of ACE2 binding by engaging the spike protein trimer.
- Ensovibep effectively inhibited frequent SARS-CoV-2 variants, including Omicron BA.1 and BA.2.
- Ensovibep reduced fatality in infected hamsters and suppressed the emergence of escape mutations in vitro.
Conclusions:
- Ensovibep exhibits broad variant activity and a promising safety profile.
- Ensovibep represents a potential alternative therapeutic for COVID-19, offering broad variant coverage.
- Further clinical evaluation of ensovibep is warranted for its use against SARS-CoV-2.
Related Concept Videos
01:30Enzyme Inhibition
79.3K
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
79.3K
02:34Inhibition of Cdk Activity
4.9K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
01:05Single Nucleotide Polymorphisms-SNPs
15.7K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.7K
01:27Combined Effects of Drugs: Synergism
4.6K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
4.6K