Evaluation of flavonoids as 2019-nCoV cell entry inhibitor through molecular docking and pharmacological analysis

Abstract

The outbreak of Coronavirus Disease 2019 (COVID-19) has been declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), which is being rapidly spread by the extremely spreadable and pathogenic 2019 novel coronavirus (2019-nCoV), also known as SARS-CoV-2. Pandemic incidence of COVID-19 has created a severe threat to global public health, necessitating the development of effective drugs or inhibitors or therapeutics agents against SARS-CoV-2. Spike protein (S) of the SARS-CoV-2 plays a crucial role in entering viruses into the host cell by binding to angiotensin-converting enzyme 2 (ACE-2), and this specific interaction represents a promising drug target for the identification of potential drugs. This study aimed at the receptor-binding domain of S protein (RBD of nCoV-SP) and the ACE-2 receptor as a promising target for developing drugs against SARS-CoV-2. Over 100 different flavonoids with antioxidant, anti-inflammatory, and antiviral properties from different literatures were taken as a ligand or inhibitor for molecular docking against target protein RBD of nCoV-SP and ACE-2 using PyRX and iGEMDOCK. Top flavonoids based on docking scores were selected for the pharmacokinetic study. Selected flavonoids (hesperidin, naringin, ECGC, and quercetin) showed excellent pharmacokinetics with proper absorption, solubility, permeability, distribution, metabolism, minimal toxicity, and excellent bioavailability. Molecular dynamics simulation studies up to 100 ns exhibited strong binding affinity of selected flavonoids to RBD of nCoV-SP and ACE-2, and the protein-ligand complexes were structurally stable. These identified lead flavonoids may act as potential compounds for developing effective drugs against SARS-CoV-2 by potentially inhibiting virus entry into the host cell.

Therapeutic and prophylactic effect of flavonoids inpost‐COVID‐19 therapy

“…Recent research teams characterized the interaction site of the S protein of the SARS‐CoV‐2 virus and revealed that flavonoids can bind ACE2, regulate the ACE1 and ACE2 levels, and maintain their basal levels (Bhowmik, Nandi, Prakash, & Kumar, 2021 ; Derosa, Maffioli, D'Angelo, & Di Pierro, 2021 ; El‐Missiry, Fekri, Kesar, & Othman, 2021 ; J. Gao et al, 2021 ; Gour, Manhas, Bag, Gorain, & Nandi, 2021 ; H. Chen & Du, 2020 ; Cherrak, Merzouk, & Mokhtari‐Soulimane, 2020 ; Khan et al, 2021 ; Mendonca & Soliman, 2020 ; Muchtaridi, Fauzi, Ikram, Gazzali, & Wahab, 2020 ; Omotuyi et al, 2021 ; Russo, Moccia, Spagnuolo, Tedesco, & Russo, 2020 ; Tutunchi, Naeini, Ostadrahimi, & Hosseinzadeh‐Attar, 2020 ; J. W. Yu, Wang, & Bao, 2020 ). In addition, disruption of the interaction between ACE2 and the SARS‐CoV‐2 spike protein is the main effect of flavonoids.…”

Flavonoids as Promising Antiviral Agents against SARS-CoV-2 Infection: A Mechanistic Review

“…Previous in silico studies and molecular analysis of different CoVs showed the potential antiviral effects of phytochemicals at different stages of viral biogenesis, including binding to ACE2, surface gangliosides, RdRp, viral spike protein, and viral protease in host cells and paved the way for more clinical and experimental studies [ 9 , 117 , 118 , 119 , 120 , 121 , 122 , 123 ]. Nevertheless, it should be considered that an acceptable antiviral activity in virtual screenings does not necessarily guarantee in vivo antiviral activity, and that is why an overview of flavonoids with antiviral properties in experimental studies is a further step toward the selection of natural antiviral agents.…”

Anticoronavirus and Immunomodulatory Phenolic Compounds: Opportunities and Pharmacotherapeutic Perspectives

“…This study suggests that resveratrol inhibits the entry of virus into Vero cells. In addition to the above studies, several molecular docking and computational studies have described different flavonoids that target SARS-CoV-2 S protein, 3CL pro , PL pro , helicase and RNA polymerase [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]. Molecular docking studies have also identified resveratrol, quercetin, and luteolin as phenolic compounds that binds with high affinity to ACE2 receptor [63,64].…”