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,Mohamed Ahmed Ali,Noha M Gamaleldin,Hossam M Hassan,Khayrya A Youssif,Mostafa E Rateb,Usama Ramadan Abdelmohsen,Ahmed Mostafa,Yassmin Moatasim,Yasser Gaber,Ahmed M Sayed,Omnia Kutkat

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.

Highlights

SARS CoV-2 (COVID-19) is a newly emerged pandemic triggered by the severe acute respiratory syndrome coronavirus-2 that created an unprecedented global health crisis [1]
Enormous in silico studies were conducted at the beginning of the crisis, and they suggested a wide range of natural products from several chemical classes to be promising anti-SARS CoV-2 agents [12,13]. In this investigation and as a part of our ongoing investigation of natural products for developing new effective anti-COVID-19 therapeutics, we found that the C. benedictus extract (CBE) could potentially inhibit viral replication in vitro
We reviewed all of the compounds previously reported from C. benedictus (Figure 3)

Summary

Introduction

SARS CoV-2 (COVID-19) is a newly emerged pandemic triggered by the severe acute respiratory syndrome coronavirus-2 that created an unprecedented global health crisis [1]. It is a zoonotic virus with more highly contagious properties than the Middle East respiratory syndrome virus (MERS CoV) [2]. SARS CoV-2 is a positive-sense, single-stranded RNA β-coronavirus that infects mammals and is assumed to have originated from bats [5]. It has one of the biggest genomes among other RNA viruses [3,6]. Other coronaviruses can encrypt an envelope-related hemagglutinin-esterase protein (HE) [3]

Methods

Results

Conclusion