B-T hybrids with a Potential to Inhibit the Viral Replication of SARS -CoV-2

Identifying the Issue

COVID-19 is the largest global pandemic currently and it has emerged as the deadliest infection of the century. It’s still critical to find novel compounds that can inhibit viral replication, in turn reducing the pace of infection.

Objective of the Research

• To design and synthesise benzoxazole-thiazolidinone hybrids (B-T hybrids) using a facile synthetic route.
• To analyse the inhibitory potential of designed B-T hybrids against the SARS-CoV-2 proteases using an in-silico approach.

Who should read this?

COVID-19 Researchers, Medicinal Chemists and Pharmaceutical Industry.

Solution

Hybrid molecules represent a relatively recent area in drug research with promising results.

The two scaffolds (benzoxazole and thiazolidinone) exhibit a wide spectrum of pharmacological activities and showed antiviral efficacy (both in vitro and in vivo) against a variety of viruses.

The hybrids derived from these two scaffolds share a similarity (structurally) with some of the active compounds screened in vitro against SARS-CoV-2.

This motivated us to screen the benzoxazole–thiazolidinone hybrids as SARS-CoV-2 protease inhibitors. In order to achieve this, a combination of docking, dynamics, and free energy studies were employed in this study.

Key Features and Benefits

• Established the key interactions between the B-T hybrids and SARS-CoV-2 proteases.
• A simple four-step synthetic procedure was developed to synthesise the B-T hybrids.
• Identifying a novel compound (MBT9) that could act as an allosteric inhibitor of PLp, thus inhibits viral replication, in turn reducing the pace of infection.

Impact

• This study is related to the COVID-19 research and contributes to the understanding of SARS-CoV-2.
• The in-vivo and in-vitro studies could be carried out to further evaluate the therapeutic potential of the proposed ligands.
• The potential of the B-T hybrids as covalent binders to 3CLp can also be explored, as the conjugate amide group present in the thiazolidinone scaffold of the molecule can serve as a Michael acceptor.

Team

Vijay Sai Krishna Cheerala, Research Scholar, Department of Chemistry, Brindavan Campus, SSSIHL

Prasanth Ghanta, Research Scholar, Department of Biosciences, Prasanthi Nilayam Campus, SSSIHL

Prof. C N Sundaresan, Professor (Hon.), Department of Chemistry, Brindavan Campus, SSSIHL

Paper Published in: RSC Advances (Royal Society of Chemistry)

Title: Design, synthesis and in silico screening of benzoxazole–thiazolidinone hybrids as potential inhibitors of SARS-CoV-2 proteases

Read Paper Here: https://pubs.rsc.org/en/content/articlelanding/2021/ra/d1ra07504g