Design, synthesis of some novel chromen derivatives and evaluation of their effectiveness as the inhibitors of SARS-CoV-2 virus 3CL protease enzyme

Title : Design, synthesis of some novel chromen derivatives and evaluation of their effectiveness as the inhibitors of SARS-CoV-2 virus 3CL protease enzyme

Abstract:

Since 2020, COVID?19 has created a major threat to the human population across the globe. There are many mutations in SARS CoV-2 like Alpha, Beta, Delta and Omicron, etc. A newly emerged SARS-CoV-2 variant B.1.1.529 has worried health policymakers worldwide due to the presence of a large number of mutations in its genomic sequence, especially in the Mpro (Omicron) protein region. But still, we are not known about the effectiveness of vaccines and drugs against all the variants. In continuation of our research in SARS CoV-2, from the hits obtained from natural compounds by in-silico drug design, we have designed some novel Chromen derivatives by molecular hybridization approach. The final designed molecules were subjected to molecular docking studies by Glide module, MMGBSA binding free energy calculations by the prime module and MD simulation studies by the Desmond module of Schrodinger suit-2021-4. The in-silico ADMET properties were predicted by using the Qikprop tool which showed the favorable pharmacokinetic profile of the compounds. Then the compounds were synthesized, and characterized by spectral studies. Finally, an In-vitro assay was carried out for all the derivatives and screened for their anti-SARS CoV-2 activity employing the 3CL Protease or Main Protease (Mpro) (B.1.1.529, Omicron Variant, P132H mutant) (SARS-CoV-2) assay Kit. The IC50 value of the test compound was found between 45.28 µM and 203.5 µM. the standard inhibitory concentration of GC376 was 38.64 µM.

Audience Take Away Notes:

• This research work explains in-silico design against the SARS-CoV-2 Omicron target.
• This research that other faculty could use to expand their research or academics.
• This research work explains the docking, ADMET, and molecular dynamics study of the hits.
• This research also explains the synthesis, characterization and in-vitro screening against the SARS CoV-2 CLpro target.
• This research work will be helpful to design novel molecules against COVID-19.

Biography:

Dr. Kalirajan Rajagopal graduated with both UG and PG in Pharmaceutical Chemistry at The Tamilnadu Dr. MGR Medical University, Chennai. He received his PhD degree in 2013 at JSS University, India. He has 24 years of teaching and research experience and currently working as a Professor and Head in the Department of Pharmaceutical Chemistry, JSS Academy of Higher Education & Research, India since July 2006. He has been nominated as a BOS member in various universities.  He Published 103 research papers with an IF range of 0.1 to 7.2 and an H-index of 16 by Scopus and 21 by Google Scholar and 9 books. Received many awards.