SARS-CoV Inhibitor

SH-42 is a potent and selective inhibitor of human Δ²⁴-dehydrocholesterol reductase (DHCR24), with an IC₅₀ of 42 nM. SH-42 can lead to a significant increase in plasma desmosterol levels of mice.

Acriflavine (Acriflavinium chloride) is a fluorescent acridine dye that can be used to label nucleic acid. Acriflavine is an antiseptic agent. Acriflavine is a potent HIF-1 inhibitor that prevents the dimerization of HIF-1α and HIF-1β subunits. Acriflavine inhibits the interaction between monocarboxylate transporter 4 (MCT4) and Basigin. Acriflavine is used in cancer research, such as breast cancer, brain tumor and chronic myeloid leukemia. Acriflavine is a potent papain-like protease (PLpro) inhibitor, which inhibits SARS-CoV-2.

Telaprevir (VX-950) is a highly selective, reversible, and potent peptidomimetic inhibitor of the HCV NS3-4A protease, the steady-state inhibitory constant (K_i) of Telaprevir is 7 nM against a genotype 1 (H strain) NS3 protease domain plus a NS4A cofactor peptide. Telaprevir inhibits SARS-CoV-2 3CL^pro activity.

Atazanavir (BMS-232632) is a highly selective and orally active HIV-1 protease inhibitor . Atazanavir is a substrate and inhibitor of CYP3A4, and an inhibitor of P-glycoprotein (P-gp). Atazanavir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 3.49 μM. Atazanavir inhibits cardiac fibrosis, hyperlipidemia and induces malignant glioma death.

TAPI-2 (TNF Protease Inhibitor 2) is a broad-spectrum inhibitor of matrix metalloprotease (MMP), tumour necrosis factorα-converting enzyme (TACE) and a disintegrin and metalloproteinase (ADAM), with an IC₅₀ of 20 μM for MMP. TAPI-2 blocks the entry of infectious SARS-CoV.

Grazoprevir potassium salt (MK-5172 potassium salt) is a selective inhibitor of Hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants, with K_is of 0.01 nM (gt1b), 0.01 nM (gt1a), 0.08 nM (gt2a), 0.15 nM (gt2b), 0.90 nM (gt3a), respectively. Grazoprevir potassium salt inhibits SARS-CoV-2 3CL^pro activity.

THAL-SNS-032 is a selective CDK9 PROTAC degrader. THAL-SNS-032 recruits CRBN to form a ternary complex with CDK9, thereby triggering ubiquitination and proteasomal degradation of CDK9. THAL-SNS-032 also induces the degradation of CDK1, CDK2 and CDK7. THAL-SNS-032 elevates pH2AX levels, reduces MCL1s expression, and activates caspase-3. THAL-SNS-032 induces cancer cell apoptosis, regulates transcription, and inhibits the replication of human cytomegalovirus (CMV) and SARS-CoV-2. THAL-SNS-032 can be used in research related to breast cancer, leukemia, cytomegalovirus infection and SARS-CoV-2 infection.

Fluphenazine dihydrochloride is a potent, orally active phenothiazine-based dopamine receptor antagonist. Fluphenazine dihydrochloride blocks neuronal voltage-gated sodium channels. Fluphenazine dihydrochloride acts primarily through antagonism of postsynaptic dopamine-2 receptors in mesolimbic, nigrostriatal, and tuberoinfundibular neural pathways. Fluphenazine dihydrochloride can antagonize Methylphenidate-induced stereotyped gnawing and inhibit climbing behaviour in mice. Fluphenazine dihydrochloride can be used for researching psychosis and painful peripheral neuropathy associated with diabetes and has potential to inhibit SARS-CoV-2.

(Z)-Guggulsterone, a constituent of Indian Ayurvedic medicinal plant Commiphora mukul, inhibits the growth of human prostate cancer cells by causing apoptosis. (Z)-Guggulsterone inhibits angiogenesis by suppressing the VEGF–VEGF-R2–Akt signaling axis. (Z)-Guggulsterone is also a potent FXR antagonist. (Z)-Guggulsterone reduces ACE2 expression and SARS-CoV-2 infection.

Carmofur (HCFU) is a rat recombinant acid ceramidase inhibitor with an IC₅₀ of 29 nM. Carmofur is also a protease inhibitor of SARS-CoV-2 main protease (Mpro), fatty acid amide hydrolase (FAAH) and N-acylethanolamine acid amidase (NAAA). Carmofur has anti-cancer, anti-inflammatory and anti-virus activities, and can be used for the study of COVID-19 and acute lung injury (ALI).

Narsoplimab (OMS 721) is a high-affinity fully human immunoglobulin gamma 4 (IgG4) monoclonal antibody that binds MASP-2 and blocks lectin pathway activation. Narsoplimab can be used in research of hematopoietic stem-cell transplantation and SARS-CoV-2.

Pyrrothiogatain is a transcription factor GATA3 inhibitor with an IC₅₀ of 54.7 μM. Pyrrothiogatain inhibits the DNA-binding activity of GATA3 and inhibits the T helper 2 (Th2) cell differentiation and expression of Th2 cytokines. Pyrrothiogatain shows anti-infection effect by inhibiting ACE2 expression. Pyrrothiogatain can be used for the researches of inflammation, immunology, infection and cancer, such as colon cancer and SARS-CoV-2 infection.

AMY-101 TFA (Cp40 TFA), a peptidic inhibitor of the central complement component C3 (K_D = 0.5 nM), inhibits naturally occurring periodontitis in non-human primates (NHPs). AMY-101 (Cp40) exhibits a favorable anti-inflammatory activity in models with COVID-19 severe pneumonia with systemic hyper inflammation.

Sotrovimab (VIR 7831) is a human IgG1κ pan-sarbecovirus monoclonal antibody (mAb), neutralizes SARS-CoV-2, SARS-CoV-1, and multiple other sarbecoviruses. Sotrovimab is developed based on S309, exhibits a long half-life and great bioavailability in the respiratory mucosa. Sotrovimab could result in immune-mediated viral clearance and prevent progression of Covid-19 early in the course of disease.

Mefloquine hydrochloride (Mefloquin hydrochloride), a quinoline antimalarial agent, is an anti-SARS-CoV-2 entry inhibitor. Mefloquine hydrochloride is also a K⁺ channel (KvQT1/minK) antagonist with an IC₅₀ of ~1 μM. Mefloquine hydrochloride can be used for malaria, systemic lupus erythematosus and cancer research.

AMY-101 (Cp40), a peptidic inhibitor of the central complement component C3 (K_D = 0.5 nM), inhibits naturally occurring periodontitis in non-human primates (NHPs). AMY-101 (Cp40) exhibits a favorable anti-inflammatory activity in models with COVID-19 severe pneumonia with systemic hyper inflammation.

GRL0617 is a selective and competitive noncovalent inhibitor of severe acute respiratory syndrome (SARS-CoV) papain-like protease (PLpro), with an IC₅₀ of 0.6 μM and a Ki value of 0.49 μM. GRL0617 also inhibits SARS-CoV with an EC₅₀ of 14.5 μM. GRL0617 can be used for the research of severe acute respiratory syndrome.

Ibuzatrelvir (PF-07817883), a second-generation, orally bioavailable, is SARS-CoV-2 main protease (M^pro and 3CL^pro) inhibitor with improved metabolic stability. Ibuzatrelvir has demonstrated pan-human coronavirus antiviral activity and off-target selectivity profile in vitro and in preclinical animal studies. Ibuzatrelvir is well tolerated with a safety profile similar to placebo and prevents viral infection and transmission. Ibuzatrelvir can be used to inhibit COVID-19.

Enoxaparin (PK 10169), a low-molecular-weight heparin (LMWH) derivative. Enoxaparin exerts anticoagulant activity through antithrombin III, an endogenous inhibitor of factor Xa and thrombin IIa. Enoxaparin protect the rat hippocampus against TBI (traumatic brain injury) via antioxidant and anti-inflammatory properties. Enoxaparin can be used for the research of deep vein thrombosis (DVT), pulmonary embolism, TBI and COVID-19.

Ensitrelvir (S-217622) is the first orally active non-covalent, non-peptidic, SARS-CoV-2 3CL protease inhibitor (IC₅₀=13 nM).