SARS 3CLpro-IN-1

SARS 3CLpro-IN-1 (Compound 3b) is a stereo-specific SARS 3CL protease inhibitor from the octahydroisochromene scaffold, exhibiting inhibition of the P1 site imidazole with an IC50 value of 95 μM [1].

SARS-CoV-2 3CLpro-IN-1 (Compound 14c) is a highly potent inhibitor specifically designed to target and inhibit the activity of SARS-CoV-2 3CL pro, a cysteine protease found in the main coronaviruses. This enzyme is a promising target for antiviral drug development, positioning SARS-CoV-2 3CLpro-IN-1 as significant for advancing research in infectious diseases [1].

Velpatasvir (GS-5816), also known as GS-5816, is a potent and selective Hepatitis C virus NS5A inhibitor. GS-5816 has demonstrated pan-genotypic activity and a high barrier to resistance in HCV replicon assays. GS-5816 demonstrated pangenotypic antiviral activity in patients with genotype 1-4 HCV infection. It will be further evaluated in combination with other pangenotypic direct-acting antivirals to achieve the goal of developing a well-tolerated, highly effective treatment for all HCV genotypes.

CCF0058981 (CCF981) is a 3-chlorophenyl analogue, serving as a noncovalent inhibitor of SARS-CoV-2 3CL pro (SC2), demonstrating potent activity with an IC50 of 68 nM. It also exhibits inhibitory effects against SARS-CoV-1 3CL pro (SC1) with an IC50 of 19 nM, highlighting its antiviral efficacy and potential in COVID-19 research [1].

3CPLro-IN-1 (compound A17) is a potent, orally active inhibitor of SARS-CoV-2 3-Chymotrypsin-like cysteine protease (3CLpro) with an IC50 of 5.65 μM, making it an attractive drug target against COVID-19 and also considered an antitumor agent-51.

SARS-CoV-2 3CLpro-IN-10(5d) is a potent inhibitor of the SARS-CoV-2 3CL protease with an IC50 value of 190 nM and demonstrates broad-spectrum antiviral activity, exhibiting IC50 values of 790 nM for SARS-CoV-1 and 70 nM for MERS-CoV.

SARS-CoV-2 3CLpro-IN-11(11d) is a broad-spectrum antiviral compound that inhibits the SARS-CoV-2 3CL protease with an IC50 of 140 nM, and also exhibits inhibitory activity against SARS-CoV-1 and MERS-CoV with IC50 values of 240 nM and 70 nM, respectively.

SARS-CoV-2 3CLpro-IN-5 is a covalent inhibitor targeting the 3C-like protease (3CLpro), with potent inhibitory activity (IC50: 3.8 nM) and 9.0% oral bioavailability (BA), used in COVID-19 research [1].

SARS-CoV-2 3CLpro-IN-13 is a potent inhibitor of the SARS-CoV-2 3CL protease, exhibiting significant anti-coronavirus activity with an IC50 value of 21 nM [1].

SARS-CoV-2-IN-41 (compound 2) is a potent SARS-CoV-2 3CL protease inhibitor with an IC50 of 0.022 µM, demonstrating significant antiviral efficacy [1].

SARS-CoV-2 3CLpro-IN-19 (Compound C5a), a non-covalent, non-peptide inhibitor of the SARS-CoV-2 3CLpro enzyme, exhibits potent in vitro activity with an IC50 of 0.7 μM. It demonstrates broad-spectrum efficacy against infection by Omicron subvariants (BA.5, BQ.1.1, and XBB.1.5) in human cells, with EC50 values ranging from 30-69 nM [1].

SARS-CoV-2 3CLpro-IN-14 (compound 11j) is an orally active inhibitor of SARS-CoV-2 3CLpro, demonstrating potent anti-SARS-CoV-2 properties with an EC50 of 0.18 μM and exhibits minimal cytotoxicity, having a CC50 greater than 50 μM, in Vero E6 cells [1].

Compound 3h, also known as SARS-CoV-2 3CLpro-IN-17, is a selective inhibitor of the SARS-CoV-2 3CL protease, demonstrating an IC50 of 0.322 μM [1].

SARS-CoV-2 3CLpro-IN-18 (Compound 3C) is a covalent inhibitor of SARS-CoV-2 3CLpro with an IC50 of 0.478 μM. It inhibits SARS-CoV-2 in Vero E6 cells with an EC50 of 2.499 μM and exhibits low cytotoxicity (CC50 > 200 μM) [1].

SARS-CoV-2 3CLpro-IN-21 (Compound D6) is an irreversible, covalent inhibitor of SARS-CoV-2 3CL pro, demonstrating potent inhibition with an IC50 of 0.03 μM. It also exhibits inhibitory activity against SARS-CoV-1 3CL pro with an IC50 of 0.12 μM [1].

Antcin-B exhibits a high-affinity inhibition of 3CLPro, which is potentially significant in SARS-CoV-2 research [1].

SARS-CoV-2 3CLpro-IN-15 (compound a), a beta-nitrostyrene derivative, inhibits the SARS-CoV-2 3CL protease (3CLpro), thereby suppressing viral replication and transcription. It is instrumental in identifying potential anti-COVID-19 lead compounds [1].

SARS-CoV-2-IN-80 (compound 13), identified as a potent inhibitor of SARS-CoV-2 3CLpro, exhibits an IC50 value of 0.964 µM [1].

SARS-CoV-IN-5 (compound 49) is a high-selectivity, non-peptide, non-covalent 3CLpro inhibitor. It exhibits IC50 values of 38 nM, 21.1 nM, and 86 nM against the 3CLpro of SARS-CoV-1, SARS-CoV-2, and bat coronavirus WIV1, respectively. SARS-CoV-IN-5 inhibits the replication of the SARS-CoV-2 Delta variant with an EC50 of 0.272 μM. The compound notably reduces viral copy numbers in the lungs of K18-hACE2 transgenic mouse model. Furthermore, SARS-CoV-IN-5 demonstrates broad-spectrum antiviral activity against SARS-CoV-1, WIV1, MERS, HCoV-OC43, HCoV-229E, and HKU9, targeting these coronaviruses effectively.

PF-00835231 is a CoV-2 cysteine 3C-like protease (3CLpro) inhibitor, with IC50s of 0.27 nM and 4 nM for SARS CoV-2 and SARS CoV-1 3CLpro, respectively. PF-00835231 is the active compound of the first anti-3CLpro regimen in clinical trials.

YH-53 is a potent 3CLpro inhibitor, exhibiting K i values of 6.3 nM and 34.7 nM against SARS-CoV-1 3CLpro and SARS-CoV-2 3CLpro, respectively. This peptidomimetic compound, characterized by its unique benzothiazolyl ketone structure, significantly inhibits SARS-CoV-2 replication, highlighting its potential in COVID-19 research [1] [2].