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.

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.

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.

Adintrevimab (ADG 20), a human IgG1 monoclonal antibody, targets SARS-CoV (SARS-CoV) and demonstrates inhibition against SARS-CoV-2 variants as well as other SARS-like coronaviruses with pandemic potential [1].

CTSL/CAPN1-IN-2 (Compound 14b) serves as an orally active inhibitor targeting both CTSL and CAPN1, manifesting IC50 values of 6.88 nM for CTSL and 347.6 nM for CAPN1 respectively. This compound not only displays anti-inflammatory attributes but also features favorable pharmacokinetic properties. Moreover, CTSL/CAPN1-IN-2 shows extensive antiviral effects against coronaviruses by inhibiting viral entry [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.