26 March 2020
The recent outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in December 2019 raised global health concerns. The viral 3-chymotrypsin-like cysteine protease (3CL pro) enzyme controls coronavirus replication and is essential for its life cycle. 3CL pro is a proven drug discovery target in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of SARS-CoV. Therefore, herein, we analysed the 3CL pro sequence, constructed its 3D homology model, and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds. Our analyses revealed that the top nine hits might serve as potential anti- SARS-CoV-2 lead molecules for further optimisation and drug development process to combat COVID-19.
SARS-CoV-2 3CL pro is conserved, share 99.02% sequence identity with SARS-CoV 3CL pro and together with 12 point-mutations.
Mutations disrupt important hydrogen bonds and alter the receptor binding site of SARS-CoV-2 3CL pro.
Medicinal plants phytochemicals were proved potential anti-COVID-19 druggable candidates.