Therapeutic Potential of Antiviral Peptides against the NS2B/NS3 Protease of Zika Virus.

The NS2B/NS3 protease is highly conserved among various proteases of the Zika virus, making it an important therapeutic target for developing broad-spectrum antiviral drugs. The NS2B/NS3 protease is a crucial enzyme in the replication cycle of Zika virus and plays a significant role in viral maturation and assembly. Inhibiting the activity of this protease can potentially prevent viral replication, making it an attractive target for developing therapies against Zika virus infection. This work screens 429 antiviral peptides in comparison with substrate peptide against the NS2B/NS3 of Zika virus using molecular docking and molecular dynamics (MD) simulation. Based on the docking screening, MD simulation conducted for the best four peptides including AVP0239, AVP0642, AVP0660, and AVP2044, could be effective against NS2B/NS3. These results were compared with the control substrate peptide. Further analysis indicates that AVP0642 and AVP2044 are the most promising candidates. The interaction analysis showed that the catalytic site residues including His51, Asp75, Ser135 and other non-catalytic residues such as Asp129, Asp83, and Asp79 contribute substantial interactions. Hydrogen bonds (41%) and hydrophobic interactions (33%) are observed as the prominent non-covalent interaction prompting the peptide-protein complex formation. Furthermore, the structure-activity relationship (SAR) illustrates that positively charged (Lys, Arg) residues in the peptides dominate the interactions. This study provides the basis for developing novel peptide-based protease inhibitors for Zika virus.

A student led computational screening of peptide inhibitors against main protease of SARS-CoV-2.

The main protease of SARS-CoV-2 is a promising drug target due to its functional role as a catalytic dyad in mediating proteolysis during the viral life cycle. In this study, experimentally proven 14 HIV protease peptides were screened against the main protease of SARS-CoV-2. Fourteen middle and high school "student researchers" were trained on relevant computational tools, provided with necessary biological and chemical background and scientific article writing. They performed the primary screening via molecular docking and the best performing complexes were subjected to molecular dynamics simulations. Molecular docking revealed that HIP82 and HIP1079 can bind with the catalytic residues, however after molecular dynamics simulation only HIP1079 retained its interaction with the catalytic sites. The student researchers were also trained to write scientific article and were involved with drafting of the manuscript. This project provided the student researchers an insight into multi-disciplinary research in biology and chemistry, inspired them about practical approaches of computational chemistry in solving a real-world problem like a global pandemic. This project also serves as an example to introduce scientific inquiry, research methodology, critical thinking, scientific writing, and communication for high school students.