Objective:

2

To select potential molecules that can target viral spike proteins

which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening.

Methods:

2

The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly

approximately 15

000 molecular candidates were prepared

including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP)

for the docking process. Then

virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally

the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper.

Results:

2

It was found that digitoxin

a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly

two of the CM herbs containing the natural compounds that had relatively high binding scores

Forsythiae fructus

and

Isatidis radix

are components of Lianhua Qingwen (莲花清瘟)

a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover

raltegravir

an HIV integrase inhibitor

was found to have a relatively high binding score.

Conclusions:

2

A class of compounds

which are from FDA-approved drugs and CM natural compounds

that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection

and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.