Virtual screening based on the structure of more than 105 compounds against four key proteins of SARS-CoV-2: MPro, SRBD, RdRp, and PLpro

Farzan Nabati; Ayshin Kamyabiamineh; Ramin Kosari; Faezeh Ghasemi; Seyedehmasoumeh Seyedebrahimi; Sobhan Mohammadi; Mohammad Moradi

doi:10.1016/j.imu.2022.101134

Virtual screening based on the structure of more than 10⁵ compounds against four key proteins of SARS-CoV-2: M_Pro, S_RBD, RdRp, and PL_pro

Inform Med Unlocked. 2022:35:101134. doi: 10.1016/j.imu.2022.101134. Epub 2022 Nov 12.

Authors

Farzan Nabati¹, Ayshin Kamyabiamineh², Ramin Kosari³, Faezeh Ghasemi⁴, Seyedehmasoumeh Seyedebrahimi⁵, Sobhan Mohammadi⁶, Mohammad Moradi¹

Affiliations

¹ Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
² Manzoumeh kherad institute, Tehran, Iran.
³ Department of Allied Medicine, Tehran Universityy of Medical Sciences, Tehran, Iran.
⁴ Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Next to Milad Tower, Tehran, Iran.
⁵ Department of Allied Medicine, Babol University of Medical Sciences, Babol, Iran.
⁶ Department of Allied Medicine, Shahid Beheshti Universityy of Medical Sciences, Tehran, Iran.

Abstract

Background: SARS-CoV-2 initially originated in Wuhan (China) around December 2019, and spread all over the world. Currently, WHO (Word Health Organization) has licensed several vaccines for this viral infection. However, not everyone can be vaccinated. People with underlying health conditions that weaken their immune systems or those with severe allergies to some vaccine components, may not be able to be vaccinated. Moreover, no vaccination is 100% safe, and the emergence of new SARS-CoV-2 mutations may reduce the efficacy of immunizations. Therefore, it is urgent to develop effective drugs to protect people against this virus.

Material and method: We performed structure-based virtual screening (SBVS) of a library that was built from ChemDiv and PubChem databases against four SARS-CoV-2 target proteins: S-protein (spike), main protease (M_Pro), RNA-dependent RNA polymerase, and PL_pro. A virtual screening study was performed using PyRx and AutoDock tools.

Results: Our results suggest that twenty-five top-ranked drugs with the highest energy binding as the potential inhibitors against four SARS-CoV-2 targets, relative to the reference molecules. Based on the energy binding, we suggest that these compounds could be used to produce effective anti-viral drugs against SARS-CoV-2.

Conclusion: The discovery of novel compounds for COVID-19 using computer-aided drug discovery tools requires knowledge of the structure of coronavirus and various target proteins of the virus. These compounds should be further assessed in experimental assays and clinical trials to validate their actual activity against the disease. These findings may contribute to the drug design studies against COVID-19.

Keywords: Molecular docking; Mpro; PLpro, virtual screening; RdRp; SARS-CoV-2; SRBD.