Location
Suwanee, GA
Start Date
7-5-2024 1:00 PM
End Date
7-5-2024 4:00 PM
Description
The lingering consequences of the COVID-19 pandemic continue to manifest as persistent effects on recovering patients. Recent research has identified RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like protease (3CLpro), and papain-like protease (PLpro) as crucial components for SARS-CoV-2 replication and the regulation of the host's immune response. Specifically, 3CLpro plays a pivotal role by cleaving 11 non-structural protein (NSPs) sites on the polyprotein of coronaviruses. Consequently, 3CLpro is an attractive target for potential antiviral drug development, with the potential to inhibit viral RNA production in SARS-CoV-2. Our study examined the inhibitory effects of 21 tanshinone derivatives on the SARS-CoV-2 3CLpro enzyme. Among these 21 compounds, seven tanshinone derivatives - namely 3alpha-hydroxytanshinone IIA, dihydroisotanshinone, dihydrotanshinone, 1,2-dihydrocryptotanshinone, 1,2 dihydrocryptotanshinone IIA, Dihydrotanshinone II, and tanshinone IIA - demonstrated an inhibitory effect on 3CLpro exceeding 50% at a concentration of 50uM. Moreover, our dose-response studies revealed IC50 values for these compounds ranging from 0.663 μM to 11.97 μM. Our data suggest that these seven tanshinone derivatives may be used to inhibit the replicative activity of the 3CLpro. We are actively investigating these derivatives' inhibition mechanisms and cytotoxicity in vitro. Once evaluated, the pre-clinical studies must validate these derivatives' therapeutic potential and safety before considering them for clinical trials.
Embargo Period
7-2-2024
Included in
Inhibitory effect of tanshinone derivatives against SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) enzyme
Suwanee, GA
The lingering consequences of the COVID-19 pandemic continue to manifest as persistent effects on recovering patients. Recent research has identified RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like protease (3CLpro), and papain-like protease (PLpro) as crucial components for SARS-CoV-2 replication and the regulation of the host's immune response. Specifically, 3CLpro plays a pivotal role by cleaving 11 non-structural protein (NSPs) sites on the polyprotein of coronaviruses. Consequently, 3CLpro is an attractive target for potential antiviral drug development, with the potential to inhibit viral RNA production in SARS-CoV-2. Our study examined the inhibitory effects of 21 tanshinone derivatives on the SARS-CoV-2 3CLpro enzyme. Among these 21 compounds, seven tanshinone derivatives - namely 3alpha-hydroxytanshinone IIA, dihydroisotanshinone, dihydrotanshinone, 1,2-dihydrocryptotanshinone, 1,2 dihydrocryptotanshinone IIA, Dihydrotanshinone II, and tanshinone IIA - demonstrated an inhibitory effect on 3CLpro exceeding 50% at a concentration of 50uM. Moreover, our dose-response studies revealed IC50 values for these compounds ranging from 0.663 μM to 11.97 μM. Our data suggest that these seven tanshinone derivatives may be used to inhibit the replicative activity of the 3CLpro. We are actively investigating these derivatives' inhibition mechanisms and cytotoxicity in vitro. Once evaluated, the pre-clinical studies must validate these derivatives' therapeutic potential and safety before considering them for clinical trials.
Comments
Presented by Aribah Ali.