ACE2-based and Proline-rich Peptides Targeting SARS-CoV-2 Spike Receptor-Binding Domain Bound with ACE2
Disciplines
Analytical Chemistry | Biochemistry | Bioinformatics | Computational Chemistry | Medicinal-Pharmaceutical Chemistry | Other Immunology and Infectious Disease
Abstract (300 words maximum)
The coronavirus pandemic, which is also referred to as Covid-19, was first recognized in December of 2019. On 11 March 2020 the World Health Organization classified the outbreak as a pandemic. Since this classification, there have been over 457 million reported cases and 6 million deaths. To combat this virus many pharmaceutical companies such as Moderna, Pfizer, and Janssen have created mRNA and adenovirus vector-based vaccines. Though both types of vaccines have been proven to decrease the spread and severity of infection, the virus continues to spread rapidly and kill thousands of people daily. The SARS-CoV-2 virus has four structural proteins labeled as spike, envelope, membrane, and nucleocapsid proteins. The spike protein is liable for the host attachment and fusion of the viral and host-cell membranes. In this study, ACE2-based and proline-rich antiviral peptides were computationally screened against the SARS-CoV-2 spike receptor-binding domain bound with ACE2. The three-dimensional structures of these peptides were modeled by the bioinformatics tools PEP-FOLD and SWISS-MODEL, and successive molecular docking and refinement were then conducted by PATCH-DOCK and FIRE-DOCK. Alpha-helix peptide containing 33 amino acids showed the highest binding affinity of -52.48 kcal/mol. Long peptides showed lower binding affinity and interactions compared to the short peptides. Proline-rich peptides also exhibited promise inhibiting the receptor-binding domain bound with ACE2 complex. The best peptides are synthesized using standard Fmoc-based synthesis protocols. The synthesized peptides are purified using RP-HPLC and characterized by mass spectrometry and circular dichroism (CD).
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
ACE2-based and Proline-rich Peptides Targeting SARS-CoV-2 Spike Receptor-Binding Domain Bound with ACE2
The coronavirus pandemic, which is also referred to as Covid-19, was first recognized in December of 2019. On 11 March 2020 the World Health Organization classified the outbreak as a pandemic. Since this classification, there have been over 457 million reported cases and 6 million deaths. To combat this virus many pharmaceutical companies such as Moderna, Pfizer, and Janssen have created mRNA and adenovirus vector-based vaccines. Though both types of vaccines have been proven to decrease the spread and severity of infection, the virus continues to spread rapidly and kill thousands of people daily. The SARS-CoV-2 virus has four structural proteins labeled as spike, envelope, membrane, and nucleocapsid proteins. The spike protein is liable for the host attachment and fusion of the viral and host-cell membranes. In this study, ACE2-based and proline-rich antiviral peptides were computationally screened against the SARS-CoV-2 spike receptor-binding domain bound with ACE2. The three-dimensional structures of these peptides were modeled by the bioinformatics tools PEP-FOLD and SWISS-MODEL, and successive molecular docking and refinement were then conducted by PATCH-DOCK and FIRE-DOCK. Alpha-helix peptide containing 33 amino acids showed the highest binding affinity of -52.48 kcal/mol. Long peptides showed lower binding affinity and interactions compared to the short peptides. Proline-rich peptides also exhibited promise inhibiting the receptor-binding domain bound with ACE2 complex. The best peptides are synthesized using standard Fmoc-based synthesis protocols. The synthesized peptides are purified using RP-HPLC and characterized by mass spectrometry and circular dichroism (CD).