Project Title

Repurposing Highly Potent Antiviral Peptide Targeting 3-Chemotrypsin Like Protease (3CLpro) of SARS-CoV-2

Academic department under which the project should be listed

CSM - Chemistry and Biochemistry

Faculty Sponsor Name

Dr. Mohammad A. Halim

Disciplines

Biochemistry | Bioinformatics

Abstract (300 words maximum)

Beginning in 2020, the Covid-19 outbreak became a global epidemic by spreading exponentially and affecting millions worldwide. As of October 2021, more than 244 million cases have been confirmed worldwide and nearly 5 million deaths have resulted from the pandemic. Currently, major biopharmaceutical companies like Pfizer and Moderna have created and distributed FDA-approved vaccines to contain the virus. Although the vaccines showed good efficacy and significantly lowered the infection rate, the emerging variants are still infecting millions and killing thousands of people every day. While various small molecules have demonstrated promising results targeting the viral proteases such as the main and papain-like proteases, few studies have been reported for antiviral peptides. 3-chymotrypsin like protease – commonly referred to as 3CLpro – is one of the most promising targets for repurposing small drug molecules and antiviral peptides. In this study, 50 highly potent antiviral peptides that previously exhibited various levels of experimentally proven antiviral activity were selected for repurposing against the main protease of SARS-CoV-2 based on their binding affinities and non-bonding interactions with 3CLpro. These peptides were examined using various bioinformatics tools such as PEP-FOLD, PATCH-DOCK, and FIRE-DOCK. The three-dimensional structures of these peptides were modeled by PEP-FOLD, and subsequent molecular docking and refinement were performed by PATCH-DOCK and FIRE-DOCK, respectively. The binding affinities and activities of these peptides were then analyzed and arranged in a manner such that the peptides with the strongest interactions with His41 and Cys145 (active site residues of the 3Clpro) could be identified. Of the 50 peptides, AVP1987, AVP1006, AVP1005, AVP1832, and AVP0983 presented the highest binding affinities between the ranges of -62.77 and -75.42 kcal/mol. Based on the computational results, we plan to synthesize these peptides and perform their in vitro analysis by FRET-based 3CL-protease assay.

Project Type

Poster

How will this be presented?

Yes, in person

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Repurposing Highly Potent Antiviral Peptide Targeting 3-Chemotrypsin Like Protease (3CLpro) of SARS-CoV-2

Beginning in 2020, the Covid-19 outbreak became a global epidemic by spreading exponentially and affecting millions worldwide. As of October 2021, more than 244 million cases have been confirmed worldwide and nearly 5 million deaths have resulted from the pandemic. Currently, major biopharmaceutical companies like Pfizer and Moderna have created and distributed FDA-approved vaccines to contain the virus. Although the vaccines showed good efficacy and significantly lowered the infection rate, the emerging variants are still infecting millions and killing thousands of people every day. While various small molecules have demonstrated promising results targeting the viral proteases such as the main and papain-like proteases, few studies have been reported for antiviral peptides. 3-chymotrypsin like protease – commonly referred to as 3CLpro – is one of the most promising targets for repurposing small drug molecules and antiviral peptides. In this study, 50 highly potent antiviral peptides that previously exhibited various levels of experimentally proven antiviral activity were selected for repurposing against the main protease of SARS-CoV-2 based on their binding affinities and non-bonding interactions with 3CLpro. These peptides were examined using various bioinformatics tools such as PEP-FOLD, PATCH-DOCK, and FIRE-DOCK. The three-dimensional structures of these peptides were modeled by PEP-FOLD, and subsequent molecular docking and refinement were performed by PATCH-DOCK and FIRE-DOCK, respectively. The binding affinities and activities of these peptides were then analyzed and arranged in a manner such that the peptides with the strongest interactions with His41 and Cys145 (active site residues of the 3Clpro) could be identified. Of the 50 peptides, AVP1987, AVP1006, AVP1005, AVP1832, and AVP0983 presented the highest binding affinities between the ranges of -62.77 and -75.42 kcal/mol. Based on the computational results, we plan to synthesize these peptides and perform their in vitro analysis by FRET-based 3CL-protease assay.

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