Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics
Hani A. Alhadrami,
Ahmed M. Sayed,
Hossam M. Hassan,
Khayrya A. Youssif,
Yasser Gaber,
Yassmin Moatasim,
Omnia Kutkat,
Ahmed Mostafa,
Mohamed Ahmed Ali,
Mostafa E. Rateb,
Usama Ramadan Abdelmohsen,
Noha M. Gamaleldin
Affiliations
Hani A. Alhadrami
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. BOX 80402, Jeddah 21589, Saudi Arabia
Ahmed M. Sayed
Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt
Hossam M. Hassan
Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt
Khayrya A. Youssif
Department of Pharmacognosy, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11865, Egypt
Yasser Gaber
Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt
Yassmin Moatasim
Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt
Omnia Kutkat
Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt
Ahmed Mostafa
Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt
Mohamed Ahmed Ali
Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt
Mostafa E. Rateb
School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK
Usama Ramadan Abdelmohsen
Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, New Minia 61111, Egypt
Noha M. Gamaleldin
Department of Microbiology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo 11837, Egypt
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.
