Developing Scorpion Venom Based Antiviral Peptides Targeting 3-Chemotrypsin Like Protease of SARS-CoV-2
Disciplines
Medicinal-Pharmaceutical Chemistry | Organic Chemistry
Abstract (300 words maximum)
Since the development of COVID-19, a disease caused by SARS-CoV-2, there has been a need for the development of an innovative solution to increase the bioavailability of inhibitors of SARS-CoV-2. COVID-19 has decreased the global life expectancy by 1.6 years from 2019-2020. Peptide therapeutics are effective because of their high affinity with receptors and low toxicity. Additionally, they can reduce off- target side effects because of their heightened target specificity and potency. Scorpion’s venom contains a mixture of peptides and proteins with varied bioactivities and receives great attention due to their potential application in peptide drug design and development. However, due to their hydrophobic nature, these peptides are difficult to synthesize chemically. The aim of this research is to synthesize scorpion venom peptide using chemical synthesis and test their effectiveness on inhibiting the 3-Chemotrypsin Like Protease of SARS-CoV-2. The scorpion peptide was synthesized using solid phase peptide synthesis protocol with a high swelling rink-amide resin with a loading capacity of 0.6 mmol/g and mesh size of 100-200. After the peptide synthesis, the peptide-resin complexes were cleaved with 95% TFA, 2.5% H2O, and 2.5% Triisopropylsilane. The cleaved peptides were filtered and precipitated by adding cold ether. The purity and identification of the peptide was confirmed by liquid chromatography and mass spectrometry. Three charge states of the peptide detected at m/z 1732.04, 866.52 and 578.02 which correspond to [M+H] +, [M+2H]2+ and [M+3H]3+ charge states, respectively. The inhibition efficiency of the peptide against 3CLpro was tested using FRET assay which demonstrated an IC50 value of 12.32 micromolar, indicating that 3CLpro activity was decreasing with an increase in peptide in inhibitor concentration.
Use of AI Disclaimer
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Academic department under which the project should be listed
CSM – Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad Halim
Developing Scorpion Venom Based Antiviral Peptides Targeting 3-Chemotrypsin Like Protease of SARS-CoV-2
Since the development of COVID-19, a disease caused by SARS-CoV-2, there has been a need for the development of an innovative solution to increase the bioavailability of inhibitors of SARS-CoV-2. COVID-19 has decreased the global life expectancy by 1.6 years from 2019-2020. Peptide therapeutics are effective because of their high affinity with receptors and low toxicity. Additionally, they can reduce off- target side effects because of their heightened target specificity and potency. Scorpion’s venom contains a mixture of peptides and proteins with varied bioactivities and receives great attention due to their potential application in peptide drug design and development. However, due to their hydrophobic nature, these peptides are difficult to synthesize chemically. The aim of this research is to synthesize scorpion venom peptide using chemical synthesis and test their effectiveness on inhibiting the 3-Chemotrypsin Like Protease of SARS-CoV-2. The scorpion peptide was synthesized using solid phase peptide synthesis protocol with a high swelling rink-amide resin with a loading capacity of 0.6 mmol/g and mesh size of 100-200. After the peptide synthesis, the peptide-resin complexes were cleaved with 95% TFA, 2.5% H2O, and 2.5% Triisopropylsilane. The cleaved peptides were filtered and precipitated by adding cold ether. The purity and identification of the peptide was confirmed by liquid chromatography and mass spectrometry. Three charge states of the peptide detected at m/z 1732.04, 866.52 and 578.02 which correspond to [M+H] +, [M+2H]2+ and [M+3H]3+ charge states, respectively. The inhibition efficiency of the peptide against 3CLpro was tested using FRET assay which demonstrated an IC50 value of 12.32 micromolar, indicating that 3CLpro activity was decreasing with an increase in peptide in inhibitor concentration.