Investigating the novel acetonitrile derivatives as potential SARS-CoV-2 main protease inhibitor using molecular modeling approach

Abstract

The COVID-19 is declared a pandemic by World Health Organization (WHO). It causes respiratory illness which leads to oxygen deficiency; it has affected millions of lives all around the globe. It has also been observed that people with diabetes condition are more likely to have severe symptoms when infected with the SARS-CoV2. So, continued efforts are being taken to design and discover potential anti-covid drugs. Earlier, a study reveals that the acetonitrile (2-phenyl-4H-benzopyrimedo [2,1-b]-thiazol-4-yliden) derivatives have potential anti-diabetic activity. Hence, drugs repurpose approach was used to identify the potential acetonitrile derivative targeting the main protease of SARS-CoV2. Here, ADMET, molecular docking, and molecular dynamics simulation techniques were employed, to identify potential acetonitrile compounds against the main protease. The acetonitrile compounds (A to M) show the drug-likeness properties. Next, the molecular docking and dynamics simulation study reveals that acetonitrile compounds A, F, G, and L show a higher binding affinity and have an effect on the structure and dynamics of the main protease. Furthermore, binding energy calculations reveal that the acetonitrile derivative F has a higher binding affinity with the main protease and derivative L has a lower binding affinity with the main protease. The binding affinity of acetonitrile derivatives decreases in the order of F > A > G > L with the main protease. Thus, our computational modeling study provides valuable structural and energetic information of interaction of potential acetonitrile derivatives with the main protease which could be further used as potential lead molecules against the SARS-CoV2.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• ADMET
• docking
• molecular dynamics simulation
• acetonitrile derivatives

Acknowledgments

The authors remain grateful towards Dr. A.G. Jaiswal, Principle, A.C.S. College Navapur, Nandurbar for consistent encouragement and support during this work. Vijay S Patil sincerely thanks and acknowledges the Vice-chancellor of KBCNMU Jalgaon for financial support under the Vice-Chancellor research motivation scheme (NMU/11A/VCRMS/Budget-2016-17/Science-10/85/2017).

Disclosure statement

Authors declare no conflict of interest.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.