Campesterol and dithymoquinone as a potent inhibitors of SARS cov-2 main proteases—promising drug candidates for targeting its novel variants

Abstract

The sudden outbreak of the COVID-19 pandemic has currently taken approximately 2.4 million lives, with no specific medication and fast-tracked tested vaccines for prevention. These vaccines have their own adverse effects, which have severely affected the global healthcare system. The discovery of the main protease structure of coronavirus (Mpro/Clpro) has resulted in the identification of compounds having antiviral potential, especially from the herbal system. In this study, the computer-associated drug design tools were utilised to analyze the reported phytoconstituents of Nigella sativa for their antiviral activity against the main protease. Fifty-eight compounds were subjected to pharmacological parameter analysis to determine their lead likeness in comparison to the standard drugs (chloroquine and nirmatrelvir) used in the treatment of SARS-CoV-2. Nearly 31 compounds were docked against five different SARS-CoV-2 main proteases, and all compounds showed better binding affinity and inhibition constant against the proteases. However, dithymoquinone and campesterol displayed the best binding scores and hence were further subjected to dynamics and MMPBSA study for 100 ns. The stability analysis shows that dithymoquinone and campesterol show less variation in fluctuation in residues compared to standard complexes. Moreover, dithymoquinone exhibited higher binding affinity and favorable interaction followed by campesterol as compared to the standard drug. The in silico computational analysis provides a promising hit for regulating the main proteases activity.

Communicated by Ramaswamy H. Sarma

Keywords:

• Nigella sativa
• main proteases
• phytoconstituents
• molecular dynamics simulation
• SARs-CoV-2
• COVID-19

Acknowledgement

The authors acknowledge the Office of Doctoral Studies and Research for critically reviewing the manuscript and providing the manuscript number (IU/R&D/2020-MCN0001086).

Author’s contributions

NAK has summarized, revised and edited the manuscript. EK, HT and SS have performed the analysis of data. AA, ML and SK have performed critical reviewing of the manuscript and finalized it. NK and FM have revised and edited the manuscript and IZA has conceptualized, designed and reviewed the manuscript.

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Data availability statement

Data can be made available upon request.

Disclosure statement

No potential conflict of interest was reported by the authors.

Correction Statement

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

Additional information

Funding

The authors extend their appreciation to the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research work through the project number ISP22-1.