We use cookies to enhance your experience. By continuing to browse this website, you agree to our use of cookies. More information.

A new study published on the bioRxiv* preprint server shows that a small cationic peptide called closamide may inhibit the replication and transcription of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The D-enantiomer form of closamide successfully inhibited SARS-CoV-2 replication by targeting C30 endopeptidase (3CLpro protease).

Research: The cationic peptide of rattlesnake venom was used as a scaffold to design the main protease inhibitor of D-amino acid SARS-CoV-2. Photo Credit: Dmitri Gomon/Shutterstock

Crotamine is present in the venom of Crotalus durissus terrificus, which has analgesic, antibacterial and hemolytic properties. Other drugs, such as Enalapril and Eptifibatide, are based on snake venom and approved by the U.S. Food and Drug Administration.

The advantage of the selected wild-types lies in their cell penetration properties, even in the form of D-enantiomers, with high stability and specificity, as well as selectivity for the target 3CL protease,” the research team concluded.

Isolating the peptides and administering them in low doses may help create a treatment for coronavirus disease 2019 (COVID-19) for people with serious illnesses.

The researchers expressed the SARS-CoV-2 3CLpro_GST fusion protein required for virus replication on E. coli Lemo21 cells, and then purified it. The viral protease was exposed to closamide and a modified peptide with substituted cysteine ​​residues (called L-CDP2-9) to determine the best inhibitor peptide.

The first inhibition test showed that L-CDP1, L-CDP2, L-CDP7 and L-CDP8 peptides have 80% inhibitory effect on viral proteases. They also tested the minimum concentration required for closamide to have 100% inhibition of 3CLpro protease. Achieved 100% protease inhibition at 300 µM.

L-CDP1 completely inhibits SARS-CoV-2 protease activity at 30 µM. An amino acid substituted closamide derivative called L-peptide-7 produced 100% inhibition at 60 µM.

The substitution of cysteine ​​residues, especially the substitution at position 36, increased the inhibitory activity of L-CDP7.

Fluorescence-based protease assay confirmed the conformational shape of the peptide during inhibition. L-CDP1, L-CDP7 and L-CDP8 peptides were found to be competitive inhibitors.

The results showed that these peptides directly interact with amino acid residues located in the active site or amino acids located in the protease substrate binding region, preventing the substrate from entering the active site," the researchers explained.

In order to prevent the degradation of the L-enantiomer peptide, the research team created the D-enantiomer form of CDP1 and CDP7. The reason is that D peptide is more stable; L-CDP peptide can be degraded by protease hydrolysis. Since the D peptide is the mirror image of the L peptide, the team predicted that the binding affinity and its inhibitory effect should be similar. The results show that D-CDP1 and D-CDP7 are also competitive inhibitors. Nevertheless, the interaction between D-CDP1 and SARS-CoV-2 protease is ten times stronger than that of D-CDP7.

Based on these findings, the team next used network simulation to study the molecular docking efficiency of L-CDP1 and D-CDP1. The simulation shows that the amino acid residues of the viral protease interact with the ligand, indicating that there is a potential mode of interaction.

The amino acid residue His41 seems to interact with the hydrogen bond of the Lys31 residue of L-CDP1. The remaining amino acid residues are located in the substrate binding region, confirming that the interaction is competitive inhibition.

On the other hand, the role of D-CDP1 is to place the peptide in the substrate binding zone, causing the active site of the protease to be blocked.

bioRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be regarded as conclusive, guide clinical practice/health-related behaviors or regarded as established information.

Eberle RJ et al. (2021). The cationic peptide of rattlesnake venom was used as a scaffold to design the main protease inhibitor of D-amino acid SARS-CoV-2. bioRxiv, 2021. doi: https://doi.org/10.1101/2021.11.10.468025, https://www.biorxiv.org/content/10.1101/2021.11.10.468025v1

Published in: Medical News | Medical Research News | Disease/Infection News

Tags: amino acids, determination, binding affinity, cells, coronavirus, coronavirus disease COVID-19, cysteine, drugs, fluorescence, food, ligand, peptide, protein, research, respiratory, SARS, SARS-CoV-2 , Severe acute respiratory system, severe acute respiratory syndrome, snake, syndrome, transcription, venom

Jocelyn Solis-Moreira received a bachelor's degree in comprehensive neuroscience, and then she continued her graduate research to study the long-term effects of adolescent alcoholism on brain neurochemistry in adulthood.

Please use one of the following formats to cite this article in your paper, essay, or report:

Solis Moreira, Jocelyn. (2021, November 12). Studies have shown that rattlesnake venom peptides can inhibit the replication and transcription of SARS-CoV-2. News-Medical. Retrieved on November 16, 2021 from https://www.news-medical.net/news/20211112/Study-suggests-rattlesnake-venom-peptide-inhibits-SARS-CoV-2-replication-and-transcription.aspx.

Solis Moreira, Jocelyn. "Studies have shown that rattlesnake venom peptides can inhibit the replication and transcription of SARS-CoV-2." News-Medical. November 16, 2021. <https://www.news-medical.net/news/20211112/Study-suggests-rattlesnake-venom-peptide-inhibits-SARS-CoV-2-replication-and-transcription.aspx>.

Solis Moreira, Jocelyn. "Studies have shown that rattlesnake venom peptides can inhibit the replication and transcription of SARS-CoV-2." News-Medical. https://www.news-medical.net/news/20211112/Study-suggests-rattlesnake-venom-peptide-inhibits-SARS-CoV-2-replication-and-transcription.aspx. (Accessed November 16, 2021).

Solis Moreira, Jocelyn. 2021. Studies have shown that rattlesnake venom peptides inhibit SARS-CoV-2 replication and transcription. News-Medical, accessed on November 16, 2021, https://www.news-medical.net/news/20211112/Study-suggests-rattlesnake-venom-peptide-inhibits-SARS-CoV-2-replication-and- transcription.aspx.

In this interview, we talked with Warren Mino of Smiths Detection to learn about their innovative technologies and their participation in biological threat detection.

We discussed with Dr. Philip Landrigan about his latest research on air pollution and how African countries are in a prime position to take action against it.

Dr. Mann and Dr. Shah

News-Medical discussed with Dr. Mann and Dr. Shah the Columbia Psychiatry Pathways application and its purpose to improve depression treatment.

News-Medical.Net provides this medical information service in accordance with these terms and conditions. Please note that the medical information on this website is intended to support rather than replace the relationship between patients and doctors/doctors and the medical advice they may provide.

This website complies with HONcode standards to obtain reliable health information: verify here.

News-Medical.net-AZoNetwork website

Owned and operated by AZoNetwork, © 2000-2021