2. Academic Validation
  3. Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics

Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics

  • Antibiotics (Basel). 2021 May 7;10(5):542. doi: 10.3390/antibiotics10050542.
Hani A Alhadrami 1 2,  Ahmed M Sayed 3,  Hossam M Hassan 3 4,  Khayrya A Youssif 5,  Yasser Gaber 6 7,  Yassmin Moatasim 8,  Omnia Kutkat 8,  Ahmed Mostafa 8,  Mohamed Ahmed Ali 8,  Mostafa E Rateb 9,  Usama Ramadan Abdelmohsen 10 11,  Noha M Gamaleldin 12
Affiliations

Affiliations

  • 1 Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. BOX 80402, Jeddah 21589, Saudi Arabia.
  • 2 Molecular Diagnostic Lab, King Abdulaziz University Hospital, King Abdulaziz University, P.O. BOX 80402, Jeddah 21589, Saudi Arabia.
  • 3 Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt.
  • 4 Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62513, Egypt.
  • 5 Department of Pharmacognosy, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11865, Egypt.
  • 6 Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt.
  • 7 Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Mutah University, Karak 61710, Jordan.
  • 8 Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt.
  • 9 School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK.
  • 10 Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, New Minia 61111, Egypt.
  • 11 Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
  • 12 Department of Microbiology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo 11837, Egypt.
PMID: 34066998 DOI: 10.3390/antibiotics10050542
Abstract

Since the emergence of the SARS-CoV-2 pandemic in 2019, it has remained a significant global threat, especially with the newly evolved variants. Despite the presence of different COVID-19 vaccines, the discovery of proper Antiviral therapeutics is an urgent necessity. Nature is considered as a historical trove for drug discovery, especially in global crises. During our efforts to discover potential anti-SARS CoV-2 natural therapeutics, screening our in-house Natural Products and plant crude extracts library led to the identification of C. benedictus extract as a promising candidate. To find out the main chemical constituents responsible for the extract's Antiviral activity, we utilized recently reported SARS CoV-2 structural information in comprehensive in silico investigations (e.g., ensemble docking and physics-based molecular modeling). As a result, we constructed protein-protein and protein-compound interaction networks that suggest cnicin as the most promising anti-SARS CoV-2 hit that might inhibit viral multi-targets. The subsequent in vitro validation confirmed that cnicin could impede the viral replication of SARS CoV-2 in a dose-dependent manner, with an IC50 value of 1.18 µg/mL. Furthermore, drug-like property calculations strongly recommended cnicin for further in vivo and clinical experiments. The present investigation highlighted Natural Products as crucial and readily available sources for developing Antiviral therapeutics. Additionally, it revealed the key contributions of bioinformatics and computer-aided modeling tools in accelerating the discovery rate of potential therapeutics, particularly in emergency times like the current COVID-19 pandemic.

Keywords

COVID-19; MERS CoV; SARS CoV-2; bioinformatics; blessed thistle; cnicin; in silico.

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