coronaviruses

(Rac)-X77 (MUN91789) is a potent SARS- CoV- 2 main protease inhibitor.

Merafloxacin (CI 934) is a fluoroquinolone antibacterial, which was also identified as a 1 PRF inhibitor of SARS-CoV-2.

Galidesivir is a viral RNA-dependent RNA polymerase (RdRP) inhibitor and broad spectrum antiviral nucleotide.In vitro, galidesivir displays antiviral activity against a range of RNA viruses, including bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses, and flaviviruses (EC50values range from 3 μM to >100 μM). Galidesivir protects against Ebola and Marburg viral infection in animal models.

Molnupiravir (EIDD-2801) is an isopropyl ester prodrug of the ribonucleoside analog EIDD-1931 with oral bioavailability. Molnupiravir can be used in the study of COVID-19, seasonal and pandemic influenza, and has broad-spectrum antiviral activity against multiple coronaviruses and influenza viruses, such as SARS-CoV-2, MERS-CoV, SARS-CoV.

EIDD-2801 (Molnupiravir) is an isopropylester prodrug of the ribonucleoside analog N 4-hydroxycytidine (EIDD-1931) that has shown broad influenza virus and multiple coronaviruses activity.

Alisporivir (Debio-025) is a cyclophilin A inhibitor that disrupts the interaction between CypA and NS5A. It exhibits anti-hepatitis C virus (HCV) activity in vivo and in vitro, inhibits the replication of MERS and SARS coronaviruses, and promotes antigen-specific CD8(+) T cell activation.

SARS-CoV-2-IN-101 (compound 10O) is an effective orally active inhibitor of SARS-CoV-2 with an EC50 value of 0.64 µM against HCoV-229E. This compound exhibits cytotoxicity and can reduce the expression levels of HCoV-229E N protein and RNA. Additionally, SARS-CoV-2-IN-101 has broad-spectrum antiviral activity against coronaviruses.

3CLPro-IN-3 (Compound A36) is an inhibitor of SARS-CoV-2 3CLpro with an IC50 value of 51.3 nM. It exhibits antiviral activity against human coronaviruses 229E, OC43, and the murine coronavirus MHV.

TDI-015051 is an orally active inhibitor of SARS-CoV-2 non-structural protein 14 (SARS-CoV-2 NSP14) with an IC50 of ≤0.15 nM. It effectively inhibits SARS-CoV-2 NSP14 in Huh-7.5 cells (EC50=11.4 nM) and A549 cells expressing ACE2-TMPRSS2 (EC50=64.7 nM). Additionally, TDI-015051 suppresses other coronaviruses such as α-hCoV-NL63, α-hCoV-229E, and β-hCoV-MERS with IC50 values of 1.7, 2.6, and 3.6 nM, respectively. This compound inhibits viral RNA methylation and replication by binding to a stable SAH-cap pocket and demonstrates anti-infection activity in mouse models.

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.

AB-343 is a selective covalent inhibitor of SARS-CoV-2 Mpro with an IC50 of 8 nM and a Ki of 2.8 nM. It effectively inhibits the main protease of SARS-CoV-2 and several other coronaviruses and is active against some resistant variants. AB-343 can be utilized in research related to diseases associated with coronavirus infections.

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 Mpro-IN-44 (Compound 25) is a broad-spectrum inhibitor of the main protease (Mpro) for coronaviruses. It exhibits inhibitory activity against several high-risk coronaviruses, including SARS-CoV-2 and PEDV, with an IC50 of less than 0.6 μM. The broad inhibition of coronaviruses by SARS-CoV-2 Mpro-IN-44 is achieved through enhanced interaction with conserved sites of Mpro. This compound is a potential candidate for the development of antiviral drugs against coronaviruses.

PROTACSARS-CoV-2 Mpro degrader-2 (Compound 6) is a potent SARS-CoV-2 Mpro PROTAC degrader. It exhibits broad-spectrum antiviral activity against coronaviruses, including SARS-CoV-2 (EC50 = 10.8 μM), HCoV-OC43 (EC50 = 1.6 μM), and HCoV-229E (EC50 = 6.5 μM). In Calu-3 cells, it shows effective anti-SARS-CoV-2 activity with an EC50 of 0.89 μM.

hACE2/SP-IN-1 (compound 7a) is a dual inhibitor targeting both hACE2 and the spike protein of coronaviruses. This compound can bind to the spike protein, thereby blocking cell entry and preventing SARS-CoV-2 from infecting human cells.

VD5123 is a serine protease inhibitor that targets TMPRSS2, HGFA, matriptase, and hepsin with IC50 values of 15, 3980, 140, and 37 nM, respectively. It is useful in antiviral research, particularly concerning SARS-CoV-2, as well as a wide range of coronaviruses and influenza viruses.

PROTACSARS-CoV-2 Mpro degrader-3 (Compound P2) exhibits antiviral activity by degrading the main protease (Mpro) of human coronaviruses (HCoV) with a DC50 of 27 μM. It effectively inhibits viral replication, with EC50 values of 4.6 μM for HCoV-229E and HCoV-OC43, and 0.71 μM for SARS-CoV-2.

ALG-097558 is an orally active 3CL protease inhibitor. It demonstrates broad antiviral activity against various SARS-CoV-2 variants and other human coronaviruses, including SARS-CoV-1, α-HCoV 229E, and β-HCoV OC43. ALG-097558 exhibits potent inhibitory effects, with an IC50 of 2 nM for SARS-CoV-2 3CL protease and 6 nM for 229E 3CL protease. In a SARS-CoV-2 hamster infection model, ALG-097558 shows antiviral activity and can be used for research on viral infections.

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.

AXT-914 is an inhibitor of the calcium-sensing receptor (CaSR). It exhibits antiviral activity against coronaviruses HCoV 229E and SARS-CoV2. AXT-914 reduces cytoplasmic calcium signaling activity caused by CaSR mutations. It is applicable in research on Bartter syndrome type 5, autosomal dominant hypocalcemia (ADH), and coronavirus infections.

TMP1 is an orally active dual inhibitor targeting M pro (IC50= 312.5 nM) and TMPRSS2 (IC50= 1.28 μM, KD= 10.10 μM). It shows broad-spectrum protective effects in vitro against various SARS-CoV-2 variants. In vivo, TMP1 provides cross-protection against highly pathogenic coronaviruses, including SARS-CoV-1, SARS-CoV-2, and MERS-CoV, and effectively blocks the transmission of SARS-CoV-2. Additionally, TMP1 can inhibit the infection of SARS-CoV-2 escape mutants resistant to Nivolumab. TMP1 is useful in coronavirus research.

Mpro inhibitor N3 hemihydrate is a potent antagonist of the SARS-CoV-2 main protease (Mpro), with an EC50 of 16.77 μM against SARS-CoV-2. It specifically inhibits Mpro in various coronaviruses, including SARS-CoV, MERS-CoV, HCoV-229E (IC50 4.0 μM), FIPV (IC50 8.8 μM), and MHV-A59 (IC50 2.7 μM) [1][2].

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].

ZIKV-IN-K22 is a potent antiviral agent against a broad range of coronaviruses by targeting membrane-bound viral RNA replication, effectively inhibiting ZIKV with IC50 of 2.1 μM.