rdrp-in-2

RdRP-IN-2 is an RNA-dependent RNA polymerase (RdRp) inhibitor that significantly inhibits SARS-CoV-2 RdRp with an IC50 of 41.2 µM and also inhibits Feline coronavirus (FIPV) replication.

PC786 is a potent and selective non-nucleoside RSV L-protein polymerase inhibitor for inhalation therapy of RSV infections, with antiviral activity against RSV-A (IC50=0.09-0.71 nM) and RSV-B (IC 50=1.3-50.6 nM), and the ability to inhibit RSV RNA-dependent RNA polymerase in HEp-2 cells ( RdRp).

SARS-CoV-IN-6 (Compound 17) acts as an inhibitor of SARS-CoV-1 and SARS-CoV-2 RdRp, demonstrating an IC50 value of 7.8 μM against SARS-CoV-2 RdRp. This compound reduces the cytopathic effects of single-round infectious particles (SRIP) infected with SARS-CoV-1 and SARS-CoV-2 replicons and inhibits the expression of SARS-CoVN proteins. The EC50 values for SRIP based on SARS-CoV-1 and SARS-CoV-2 replicons are 0.12 µM and 1.47 µM, respectively.

MTI013 is a selective inhibitor of SARS-CoV-2 nsp14 Mtase (IC50: 2.98 µM) and an antiviral agent (IC50: 10.33 µM in HCoV-229E infected Huh7 cells). Additionally, MTI013 demonstrates synergistic antiviral effects when used in conjunction with the RdRp inhibitor SHEN26.

HNC-1664 is an orally active inhibitor of RNA-dependent RNA polymerase (RdRP). It exhibits broad-spectrum antiviral activity against coronaviruses, including SARS-CoV-2 wild type and its variants (XBB.1.18, HK.3.1, BF.7.14, BA.1, HCoV-229E, HCoV-OC43), as well as arenaviruses. HNC-1664 also demonstrates anti-infective efficacy in a mouse model infected with the SARS-CoV-2 Delta variant.

13-TP is an inhibitor of SARS-CoV-2. It effectively suppresses in vitro RNA synthesis catalyzed by the central replication-transcription complex (C-RTC, nsp12-nsp7-nsp82) of SARS-CoV-2. 13-TP fully inhibits RdRp polymerase activity and obstructs the complete extension of some primer RNAs.

SARS-CoV-2 RdRp-IN-1 (Compound PAP-2) is a potent inhibitor of SARS-CoV-2 RdRp with an EC50 value of 1.11 μM. This compound interacts directly with SARS-CoV-2 RdRp, effectively resisting exonuclease (ExoN) activity, and demonstrates broad-spectrum antiviral activity against coronaviruses.

SARS-CoV-2-IN-73 (compound 4) is an inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).

PAN endonuclease-IN-2 (compound T-31) is a PAN endonuclease inhibitor (IC50: 0.15 μM) and has antiviral properties with broad-spectrum anti-influenza activity. PAN, as the N-terminal PA subunit of the polymerase-RNA complex, possesses a cap-dependent endonuclease (CEN) active site, facilitating RNA cleavage and initiating the synthesis of new RNA molecules. PAN endonuclease-IN-2 targets both influenza HA and RdRp complexes, thereby disrupting viral entry into host cells and impeding viral replication.

RH12 is a dual inhibitor of SARS-CoV-2-related RNA-dependent RNA polymerase (RdRp, IC50 of 4.42 nM) and human transmembrane serine protease 2 (TMPRSS2, IC50 of 4.2 nM). It demonstrates antiviral activity by inhibiting viral replication and absorption, showing 90.5% virucidal effect in Vero-E6 cells. Additionally, RH12 inhibits Calu-3 cell viability with an IC50 of 17.5 nM.

MePT-S-N-Pme is an inhibitor of SARS-CoV-2 RdRp activity. It significantly reduces reporter gene activity, with an IC50 of 7 μM in HEK 293 cells. MePT-S-N-Pme exhibits a mild inhibitory effect on nucleotide transferase activity and markedly inhibits SARS-CoV-2 replication in vitro.

SARS-CoV-2-IN-113 (Compound 24) is a sulfonyl hydrazine derivative that exhibits antiviral activity against SARS-CoV-2 infection, with an IC50 of 8.320 μM. It effectively inhibits the entry and replication of SARS-CoV-2 by downregulating genes and proteins such as Spike, ACE-2, and RdRp. SARS-CoV-2-IN-113 shows high selectivity and low cytotoxicity, making it a valuable candidate for COVID-19 research.

Nsp12-IN-2 (Compound 8), a triphosphate metabolite of 4'-thiouridine, functions as an inhibitor of SARS-CoV-2 Nsp12. It effectively suppresses the RNA-dependent RNA polymerase (RdRp) activity of the SARS-CoV-2 Nsp12-Nsp7-Nsp8 complex, halting RNA synthesis and blocking the RNA capping and NMP capping of Nsp9. Nsp12-IN-2 shows potential for research into infections caused by SARS-CoV-2, other coronaviruses, and additional RNA viruses.

Mpro/RdRp-IN-1 (Compound 1) is a dual-target inhibitor effective against SARS-CoV-2, targeting RdRp with an EC50 of 25.45 μM and Mpro with an IC50 of 125.4 μM. It exhibits an EC50 of 4.79 μM against HCoV-OC43 with a selectivity index (SI) of 10.89. Mpro/RdRp-IN-1 is used in SARS-CoV-2 infection research.

E3LigaseLigand-linker Conjugate 216 is a conjugate of the E3 ligase CRBN ligand and a linker. It is utilized in the synthesis of PROTACSARS-CoV-2 RdRp Degrader-1, which is a PROTAC degrader targeting SARS-CoV-2 RdRp.

DEMAMP is an antioxidant with the ability to scavenge DPPH and H2O2 free radicals, exhibiting IC50 values of 0.60 and 0.48 mg/mL, respectively. Molecular docking simulations suggest that DEMAMP effectively inhibits NADPH oxidase and the SARS-CoV-2 proteins Mpro and RdRp. Additionally, ADMET analysis confirms its good oral bioavailability. DEMAMP is applicable in studies related to COVID-19.

RdRP-IN-10 is an inhibitor of the RNA-dependent RNA polymerase (RdRp) in SARS-CoV-2, with an IC50 value of 5.78 μM. It forms a covalent bond with Cys114 of SARS-CoV-2 nsp8, disrupting the stable interaction between nsp8 and nsp12. RdRP-IN-10 effectively inhibits the RNA polymerization reaction mediated by SARS-CoV-2 RdRp without interfering with the RNA-RdRp complex binding and demonstrates antiviral activity in cell models. This compound is applicable for research related to SARS-CoV-2 infection.

AVG-233 is an orally available RNA-dependent RNA polymerase (RdRp) inhibitor with antiviral activity that blocks respiratory syncytial virus and SARS-CoV-2 replication.AVG-233 is used in the study of respiratory syncytial virus infections.

RdRP-IN-7, a RNA-dependent RNA polymerase (RdRp) inhibitor, demonstrates efficacy against SARS-CoV-2 infection with an inhibitory concentration (IC50) of 8.2 μM and (IC90) of 14.1 μM, alongside a cytotoxic concentration (CC90) of 79.1 μM, rendering it suitable for antiviral research [1].

SARS-CoV-2-IN-67 (Compound 16), a vitamin K derivative, exhibits anti-SARS-CoV-2 properties with an effective concentration (EC50) of 64.8 μM in VeroE6/TMPRSS2 cells and inhibits SARS-CoV-2 RdRp activity [1].

BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase (RdRp) inhibitor, is effective orally and can inhibit various SARS-CoV-2 variants. It exhibits EC 50 values of 0.62 µM for SARS-CoV-2 and 0.14 µM for HCoV-229E, demonstrating potent anti-pancoronavirus activity at submicromolar concentrations. Additionally, BPR3P0128 displays synergistic antiviral effects when used in combination with Remdesivir [1].

NITD-2 is a dengue virus (DENV) polymerase inhibitor, inhibits the DENV RdRp-mediated RNA elongation. NITD-2 penetrates cell membrane poorly. Dengue virus (DENV) is the most prevalent mosquito- borne viral pathogen in humans. Neither vaccine nor antiviral therapy is currently available for DENV.

Lamivudine triphosphate (3TCTP), a phosphorylated form of the nucleoside analogue Lamivudine, inhibits the reverse transcriptase of HIV or HBV, blocking viral replication through chain termination. It also acts as an inhibitor of the RdRp activity of the HCVNS5B subunit. Additionally, Lamivudine triphosphate can be incorporated into nascent RNA by SARS-CoV-2 RdRp, thereby preventing mutations in the newly synthesized SARS-CoV-2 RNA.

HeE1-2Tyr, a pyridobenzothiazole compound, is a potent inhibitor of flavivirus RNA-dependent RNA polymerases (RdRp). It significantly inhibits the RdRp activity of West Nile, Dengue, and SARS-CoV-2 in vitro, with an IC50 of 27.6 µM.