Repurposing of Some Natural Product Isolates as SARS-COV-2 Main Protease Inhibitors via In Vitro Cell Free and Cell-Based Antiviral Assessments and Molecular Modeling Approaches

Hossam M Abdallah; Ali M El-Halawany; Alaa Sirwi; Amr M El-Araby; Gamal A Mohamed; Sabrin R M Ibrahim; Abdulrahman E Koshak; Hani Z Asfour; Zuhier A Awan; Mahmoud A Elfaky

doi:10.3390/ph14030213

Repurposing of Some Natural Product Isolates as SARS-COV-2 Main Protease Inhibitors via In Vitro Cell Free and Cell-Based Antiviral Assessments and Molecular Modeling Approaches

Pharmaceuticals (Basel). 2021 Mar 4;14(3):213. doi: 10.3390/ph14030213.

Authors

Hossam M Abdallah^{1

2}, Ali M El-Halawany², Alaa Sirwi¹, Amr M El-Araby³, Gamal A Mohamed^{1

4}, Sabrin R M Ibrahim^{5

6}, Abdulrahman E Koshak¹, Hani Z Asfour⁷, Zuhier A Awan⁸, Mahmoud A Elfaky¹

Affiliations

¹ Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
² Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams Universit, Cairo 11566, Egypt.
⁴ Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt.
⁵ Batterjee Medical College, P.O. Box 6231, North Obhur, Prince Abdullah Al-Faisal Street, Jeddah 21442, Saudi Arabia.
⁶ Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
⁷ Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁸ Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Abstract

The emergence of the SARS-CoV-2 pandemic has prompted scientists to search for an efficient antiviral medicine to overcome the rapid spread and the marked increase in the number of patients worldwide. In this regard natural products could be a potential source of substances active against coronavirus infections. A systematic computer-aided virtual screening approach was carried out using commercially available natural products found on the Zinc Database in addition to an in-house compound library to identify potential natural product inhibitors of SARS-CoV-2 main protease (M^PRO). The top eighteen hits from the screening were selected for in vitro evaluation on the viral protease (SARS-CoV-2 M^PRO). Five compounds (naringenin, 2,3',4,5',6-pentahydroxybenzophenone, apigenin-7-O-glucoside, sennoside B, and acetoside) displayed high activity against the viral protein. Acteoside showed similar activity to the positive control GC376. The most potent compounds were tested in vitro on SARS-CoV-2 Egyptian strain where only naringenin showed moderate anti-SARS-CoV-2 activity at non-cytotoxic micromolar concentrations in vitro with a significant selectivity index (CC₅₀/IC₅₀ = 178.748/28.347 = 6.3). Moreover; a common feature pharmacophore model was generated to explain the requirements for enzyme inhibition by this diverse group of active ligands. These results pave a path for future repurposing and development of natural products to aid in the battle against COVID-19.

Keywords: SARS-CoV-2 Egyptian strain; SARS-CoV-2 main protease; acetoside; apigenin-7-O-glucoside; coronavirus; naringenin; pharmacophore; sennoside B; virtual screening.

Grants and funding

GCV19- 26- 1441/Deanship of Scientific Research (DSR) at King Abdulaziz University