MERS-CoV Infection

ALG-097558 is an orally active 3CLpro inhibitor. ALG-097558 demonstrates pan-coronavirus activity against various SARS-CoV-2 variants as well as other human coronaviruses (HCoVs) such as SARS-CoV-1, α-HCoV 229E, and β-HCoV OC43. ALG-097558 demonstrates potent inhibition with IC₅₀s of 2 nM (SARS-CoV-2 3CLpro) and 6 nM (229E 3CLpro). ALG-097558 demonstrates antiviral activity in the SARS-CoV-2 hamster infection model. ALG-097558 can be used for the study of viral infections[1].

TDI-015051 is a highly selective, orally active antiviral agent that targets the coronavirus NSP14 guanine-N7 methyltransferase. TDI-015051 binds to substrates in a non-competitive manner and forms a stable ternary complex, precisely blocking the capping and methylation processes of viral mRNA. TDI-015051 potently inhibits a variety of coronaviruses (including SARS-CoV-2 and MERS). By impairing viral replication and translation and inducing a moderate type I interferon-mediated immune response, it significantly reduces pulmonary viral load and exhibits a synergistic effect with Nirmatrelvir (HY-138687). In addition, TDI-015051 does not inhibit non-coronavirus methyltransferases, and the drug-resistant mutations it induces impair viral fitness, demonstrating excellent antiviral properties and safety. TDI-015051 can be used for research on COVID-19 and the replication mechanism of coronaviruses.The IC₅₀ values of TDI-015051 against SARS-CoV-2, α-hCoV-NL63, α-hCoV-229E, β-hCoV-MERS are 0.15 nM, 1.7 nM, 2.6 nM and 3.6 nM, respectively, and the K_a value against SARS-CoV-2 is 0.061 nM.

SB-140 is a selective, covalent PLpro inhibitor with an IC₅₀ of ≤2.5 nM against SARS-CoV-2 PLpro. SB-140 has antiviral activity against SARS-CoV-2, MERS-CoV and SARS-CoV-1.

(M)-AVI-4773 is an orally active, blood-brain barrier permeable coronaviruses M^Pro inhibitor with an IC₅₀ of 2.5 nM aginst SARS-CoV-2 M^Pro. (M)-AVI-4773 produces a rapid onset antiviral effect in mouse models of MERS-CoV and SARS-CoV-2 infection.

Chlorphenoxamine hydrochloride, an antihistamine and anticholinergic agent is a GPCR antagonist. Chlorphenoxamine hydrochloride inhibits multiple lethal viral diseases, such as SARS-CoV, MERS-CoV, EBOV and malaria. Chlorphenoxamine hydrochloride shows anti-filovirus activity against both EBOV and Marburg virus (MARV) with IC₅₀s of 1.1 μM and 6.2 μM, respectively. Chlorphenoxamine hydrochloride is used for allergic conditions, urticaria, viral diseases and Parkinson’s disease.

TMP1 is an orally active bispecific inhibitor of M pro (IC₅₀ = 312.5 nM)/TMPRSS2 (IC₅₀ = 1.28 μM, K_D = 10.10 μM). TMP1 exhibits broad protection against different SARS-CoV-2 variants in vitro. TMP1 cross-protects against highly pathogenic coronaviruses (SARS-CoV-1, SARS-CoV-2, and MERS-CoV) in vivo and effectively blocks the transmission of SARS-CoV-2. TMP1 can inhibit infection by SARS-CoV-2 escape mutants that are resistant to Nivolumab (HY-P9903). TMP1 can be used in coronavirus research.

SARS-CoV-2 3CLpro-IN-38 is a 3CLpro inhibitor with an IC₅₀ of 0.34 μM against SARS-CoV-2 3CLpro and an IC₅₀ of 0.12 μM against MERS-CoV 3CLpro. SARS-CoV-2 3CLpro-IN-38 inhibits recombinant Cathepsin L with an IC₅₀ of 5.23 nM. SARS-CoV-2 3CLpro-IN-38 inhibits cysteine proteases essential for the replication of SARS-CoV-2 and MERS-CoV, suppresses host cysteine proteases involved in coronavirus entry, blocks viral entry, and inhibits viral replication. SARS-CoV-2 3CLpro-IN-38 can be used in the research of COVID-19.

K22 is an anti-Coronaviral compound. K22 reduces double-stranded RNA. K22 displays antiviral activity beyond the Coronavirinae subfamily, namely against nidoviruses of the Torovirinae subfamily (EToV and WBV) and members of the Arteriviridae family (PRRSV, EAV). K22 displays antiviral activity against HCoV-229E.

Arcapillin is a flavonoid that can be isolated from Artemisia capillaris Thunb. Arcapillin induces dose-dependent relaxation of ileum and pulmonary artery smooth muscle, causes slight urinary bladder smooth muscle contraction at highest tested concentrations. Arcapillin binds to the active site of SARS-CoV-2 M_pro via interactions with Gln139, His163, and His164, exhibits antiviral activity against SARS-CoV-2 and MERS-CoV. Arcapillin can be used for the research of gastrointestinal disorders, COVID-19, and Middle East respiratory syndrome (MERS).