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. 2024 Feb 6:15:1291212.
doi: 10.3389/fphar.2024.1291212. eCollection 2024.

Individual ingredients of NP-101 (Thymoquinone formula) inhibit SARS-CoV-2 pseudovirus infection

Abdelrahim Maen #  1   2   3 , Betul Gok Yavuz #  4 , Yehia I Mohamed  4 , Abdullah Esmail  1 , Jianming Lu  5 , Amr Mohamed  6 , Asfar S Azmi  7 , Mohamed Kaseb  8 , Osama Kasseb  8 , Dan Li  9 , Michelle Gocio  8 , Mehmet Kocak  10 , Abdelhafez Selim  11 , Qing Ma  9 , Ahmed O Kaseb  4
Affiliations

Individual ingredients of NP-101 (Thymoquinone formula) inhibit SARS-CoV-2 pseudovirus infection

Abdelrahim Maen et al. Front Pharmacol. .

Abstract

Thymoquinone TQ, an active ingredient of Nigella Sativa, has been shown to inhibit COVID-19 symptoms in clinical trials. Thymoquinone Formulation (TQF or NP-101) is developed as a novel enteric-coated medication derivative from Nigella Sativa. TQF consists of TQ with a favorable concentration and fatty acids, including palmitic, oleic, and linoleic acids. In this study, we aimed to investigate the roles of individual ingredients of TQF on infection of SARS-CoV-2 variants in-vitro, by utilizing Murine Leukemia Virus (MLV) based pseudovirus particles. We demonstrated that NP-101, TQ, and other individual ingredients, including oleic, linoleic, and palmitic acids inhibited SARS-CoV-2 infection in the MLV-based pseudovirus model. A large, randomized phase 2 study of NP-101 is planned in outpatient COVID-19 patients.

Keywords: COVID-19; COVID-19 and anti-viral agents; Coronavirus; TQ formula; Thymoquinone TQ; fatty acids.

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Conflict of interest statement

Author JL was employed by Codex BioSolutions Inc. Authors MoK, OK, and MG were employed by Novatek Pharmaceuticals, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Pathogenesis Thymoquinone on COVID-19. SOD, Superoxide dismutase; GPx, Glutathione peroxidase; MDA, Malonaldehyde Th1, type I helper T lymphocytes; Th2, type II helper T cells; CVD, Cardiovascular disease; PIMS, Paediatric Inflammatory Multisystem Syndrome; KLD, Kawasaki-like diseases; LC3, Microtubule-associated protein 1A/1B-light chain 3; P62, protein 62.
FIGURE 2
FIGURE 2
Effects of Blackseed oil, Thymoquinone TQ and Fatty Acids on Blocking SARS-CoV-2-PP Infection of ACE2-expressing Cells. Serial dilutions of Blackseed oil, Thymoquinone TQ, Oleic acid, Linoleic acid, and Palmitic acid were tested for inhibition against an MLV-based pseudotyped virus using four different SARS-CoV-2 variant spike protein constructs (614D, Delta, United Kingdom, Brazil), in the infection of HEK293-ACE2 cells. The cell toxicities of the fatty acids on HEK293-ACE2 cells were shown as ‘Tox’. X-axis: compound concentration. The Y-axis shows relative luminescence unit (RLU), reflecting the luciferase activity and the viral infectivity. The experiments were repeated three times with independent samples giving similar results. For all panels, the data points shown are mean and s.d. for n = 3 technical replicates. IC50 values derived from curve fitting are listed in the Table below each Graph.
FIGURE 3
FIGURE 3
Effects of Oleic acid, Linoleic Acid, and Palmitic Acid in Combination with TQ or with Another Fatty Acid on Blocking SARS-CoV-2-PP Infection of ACE2-expressing Cells. Serial dilutions of oleic acid, linoleic acid and palmitic acid in the presence of 0.05 μM TQ; serial dilutions of linoleic acid and palmitic acid in the presence of 0.01 mg/mL oleic acid; serial dilutions of palmitic acid in the presence of 0.01 mg/mL linoleic acid were tested for inhibition against an MLV-based pseudotyped virus using four different SARS-CoV-2 variant spike protein constructs (614D, Delta, United Kingdom, Brazil), in the infection of HEK293-ACE2 cells. X-axis: compound concentration. Y-axis: relative luminescence unit (RLU), reflecting the luciferase activity and the viral infectivity. The experiments were repeated three times with independent samples giving similar results. For all panels, data points shown are mean and s.d. for n = 3 technical replicates. IC50 values derived from curve fitting are listed in the Table below each Graph.
FIGURE 4
FIGURE 4
Effects of TQ Formula in percentage increments in relativity to the infectivity of Sars-CoV-19 subvariants XBB.1.5 (Omicron) and 614G. Serial dilutions of oleic acid, linoleic acid and palmitic acid in the presence of 0.05 μM TQ; serial dilutions of linoleic acid and palmitic acid in the presence of 0.01 mg/mL oleic acid; serial dilutions of palmitic acid in the presence of 0.01 mg/mL linoleic acid were tested for inhibition against an MLV-based pseudotyped virus using four different SARS-CoV-2 variant spike protein constructs (614G and Omicron) in the infection of HEK293-ACE2 cells. X-axis: compound concentration. Y-axis: relative infectivity of viral component. The experiments were repeated three times with independent samples giving similar results. For all panels, data points shown are mean and s.d. for n = 3 technical replicates. IC50 values derived from curve fitting are listed in the Table below each Graph.
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