ABSTRACT
Based on screening in computational biology and biological in vitro assays, five natural products isolated from extracts of the herbal medicine toad skin, such as cinobufagin (CBFi), bufalin (BFi), arenobufagin (ABFi), telocinobufagin (TBFi), bufotalin (BFTi), were subjected to molecular docking calculations with the use of SARS-CoV-2 main protease (PDB 6LU7 and 7BTF) and top-scoring ligand-receptor complexes were obtained. The results showed that the binding energy of ABFi to the 3CL protein was -17.044kcal/mol, which was higher than CBFi and TBFi. However, the binding energy of ABFi to the RdRp protease was -23.250 kcal/mol, which was much lower than that of CBFi and TBFi, EVEN lower than that of ABFi to the 3CL protein. ABFi also has polar interactions with amino acids such as Glu811, Ser814, Ser681 and Thr680 of RdRp enzyme. The results revealed that ABFi had a moderate inhibitory effect on the cell proliferation of SARS-CoV-2 in vitro, with an inhibition rate of 61.12%, even weaker than Remdesivir. This new discovery provides us with new ideas for in-depth studies on the development of natural products with this class of structural generalizations as inhibitors of SARS-CoV-2, and provides an experimental basis for the next step of mechanistic studies.
ABSTRACT
Context: Since December 2019, the coronavirus disease 2019 (COVID-19) has broken out in Wuhan, Hubei Province, China. Due to the highly pathogenic and infectious characteristics, COVID-19 spread across China and later globally and became a severe pandemic. To date, there have been no efficacious specialized drugs to treat COVID-19. The China-issued Diagnosis and Treatment of Pneumonia Caused by Novel Coronavirus (Trial version 6) added the chloroquine phosphate to the antiviral treatment protocol for infected adults. Evidence Acquisition: In this review, government documents and authoritative guidelines on COVID-19 were collected from the official website of organizations related to health and medicine. Research articles related to chloroquine and its application for COVID-19 treatment were searched and acquired from the PubMed platform. Facts and data related to the use of chloroquine were summarized in several parts.