Discovery of 9,10-dihydrophenanthrene derivatives as SARS-CoV-2 3CLpro inhibitors for treating COVID-19

The SARS‐CoV‐2 main protease (Mpro): Structure, function, and emerging therapies for COVID‐19

“…Among all derivatives, compound C1 could dose dependently inhibit the target enzyme in a mixed manner, with an IC 50 value of 1.55 μM and a K i value of 6.09 μM. Further study suggested that this inhibitor had the potential to be a novel orally administered and broad‐spectrum antiviral agent 243 …”

“…Some other compounds, including polydatin, resveratrol, and all‐ trans retinoic acid, generated inhibitory effects against SARS‐CoV‐2 3CL pro 241,242 . A series of 9,10‐dihydrophenanthrene derivatives were synthesized to discover strong SARS‐CoV‐2 3CL pro inhibitors 243 . The preliminary SAR suggested that a suitable bulkier group at the C‐8 position displayed good inhibitory activities.…”

Rational identification of small molecules derived from 9,10-dihydrophenanthrene as potential inhibitors of 3CLpro enzyme for COVID-19 therapy: a computer-aided drug design approach

“…Through a previous study conducted by Zhang et al [ 2 ], we collected 46 small molecules derived from 9,10-dihydrophenanthrene as non-covalent inhibitors of SARS-CoV-2 3CL pro . Table 1 presents the structures of all 46 compounds as well as their corresponding half-maximal inhibitory concentration (pIC 50 = − Log IC 50 ) data in the presence of disulfiram (DSF) drug substance used as a reference in the in vitro positive control [ 43 , 44 ].…”

“…The world is experiencing an unstable situation at all poles due to the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), which has spread throughout the world and affected the majority of the community [ 1 , 2 ]. Simultaneously, various strict precautionary measures have been taken to prevent the transmission and rapid spread of COVID-19 among people.…”

“…Therefore, it has become necessary to explore non-covalent 3CL pro inhibitors with favorable drug properties, good pharmacokinetics, and high inhibitory activity against COVID-19. In this context, a recent study conducted by Zhang et al the in vitro discovery of several derivatives of 9,10-dihydrophenanthrene was reported as potential non-covalent, non-peptide inhibitors of the SARS-CoV-2-3CL pro [ 2 ]. Based on in vitro results on the suitability of 9,10-dihydrophenanthrene derivatives for the inhibition of 3CL pro , in this work, we perform a large-scale computational study aided by bioinformatics techniques to validate in vitro results and also to rationalize the design of new non-covalent inhibitors of 3CL pro as more convenient drugs against COVID-19.…”