Orthopoxvirus Inhibitor

Cytarabine, a nucleoside analog, causes S phase cell cycle arrest and inhibits DNA polymerase. Cytarabine inhibits DNA synthesis with an IC₅₀ of 16 nM. Cytarabine has antiviral effects against HSV. Cytarabine shows anti-orthopoxvirus activity.

Thymidine, a specific precursor of deoxyribonucleic acid, is used as a cell synchronizing agent. Thymidine is a DNA synthesis inhibitor that can arrest cell at G1/S boundary, prior to DNA replication.

Hydroxyurea is a cell apoptosis inducer that inhibit DNA synthesis through inhibition of ribonucleotide reductase. Hydroxyurea shows anti-orthopoxvirus activity.

Rifampicin is a potent and broad spectrum antibiotic against bacterial pathogens. Rifampicin has anti-influenza virus activities. Rifampicin shows anti-orthopoxvirus activity.

Ribavirin (ICN-1229) is an antiviral agent against a broad spectrum of viruses including HCV, HIVl, and RSV. Ribavirin also has anti-orthopoxvirus and anti-variola activities.

Cidofovir (GS 0504) is an acyclic monophosphate nucleotide analogue and CMV inhibitor with antiviral activity. Cidofovir inhibits cytomegalovirus (CMV) replication by selectively inhibiting viral DNA polymerase. Cidofovir induces apoptosis and can be used in studies of AIDS cytomegalovirus retinitis, herpes, and cancer. Cidofovir also has anti-orthopoxvirus and anti-variola activities.

Brincidofovir (CMX001), the lipid-conjugated prodrug of Cidofovir (HY-17438), is an orally available, long-acting antiviral. Brincidofovir shows activity against a broad spectrum of DNA viruses including cytomegalovirus (CMV), adenovirus (ADV), varicella zoster virus, herpes simplex virus, polyomaviruses, papillomaviruses, poxviruses, and mixed double-stranded DNA virus infections. Brincidofovir, an oral antiviral in late stage development, has proven effective against orthopoxviruses in vitro and in vivo.

Mitoxantrone is a potent topoisomerase II inhibitor. Mitoxantrone also inhibits protein kinase C (PKC) activity with an IC₅₀ of 8.5 μM. Mitoxantrone induces apoptosis of B-CLL (B-chronic lymphocytic leukaemia) cells. Mitoxantrone shows antitumor activity. Mitoxantrone also has anti-orthopoxvirus activity with EC₅₀s of 0.25 μM and and 0.8 μM for cowpox and monkeypox, respectively.

Aphidicolin is an inhibitor of DNA polymerase α and δ, prevents mitotic cell division by interfering DNA polymerase activity. Aphidicolin is an antibiotic produced by mold Cephalosporium aphidicola, inhibits cellular deoxyribonucleic acid synthesis and the growth of herpes simplex virus. Aphidicolin exhibits anti-orthopoxvirus activity and potentiates apoptosis induced by arabinosyl nucleosides in a human promyelocytic leukemia cell line.

Levofloxacin ((-)-Ofloxacin) is an orally active antibiotic and is active against both Gram-positive and Gram-negative bacteria. Levofloxacin inhibits the DNA gyrase and topoisomerase IV. Levofloxacin can be used for chronic periodontitis, airway inflammation and BK Viremia research. Levofloxacin shows anti-orthopoxvirus activity.

3-Deazaneplanocin A (DZNep) is a potent histone methyltransferase EZH2 inhibitor. 3-Deazaneplanocin A is a potent S-adenosylhomocysteine hydrolase (AHCY) inhibitor. 3-Deazaneplanocin A shows anti-orthopoxvirus activity.

Carbenoxolone disodium is the active metabolite of Glycyrrhizic acid (HY-N0184) and the inhibitor of human 11β-HSD and bacterial 3α, 20β-HSD. Carbenoxolone disodium is an uncoupling agent for gap junctions and a potent inhibitor of Vaccinia virus replication. Carbenoxolone disodium is used for the study of peptic, esophageal and oral ulceration and inflammation. Carbenoxolone disodium inhibits Vaccinia virus replication.

3-Deazaneplanocin A hydrochloride (DZNep hydrochloride) is a potent histone methyltransferase EZH2 inhibitor. 3-Deazaneplanocin A hydrochlorideis a potent S-adenosylhomocysteine hydrolase (AHCY) inhibitor. 3-Deazaneplanocin A hydrochloride also has anti-orthopoxvirus and anti-variola activities.

Coumermycin A1 is a JAK2 signal activator. Coumermycin A1 inhibits DNA Gyrase which thereby inhibits cell division in bacteria. Coumermycin A1 shows anti-orthopoxvirus activity.

Idoxuridine (5-Iodo-2′-deoxyuridine, 5-IUdR, IdUrd) is an iodinated thymidine analogue that competitively inhibits phosphorylases. Idoxuridine can inhibit viral activity, particularly viral eye infections, including herpes simplex keratitis, by inhibiting DNA polymerase and affecting viral replication. Idoxuridine against feline herpesvirus has the IC₅₀ value of 4.3 μM. Idoxuridine shows anti-orthopoxvirus activity.

Mitoxantrone dihydrochloride is a potent topoisomerase II inhibitor. Mitoxantrone dihydrochloride also inhibits protein kinase C (PKC) activity with an IC₅₀ of 8.5 μM. Mitoxantrone dihydrochloride induces apoptosis of B-CLL (B-chronic lymphocytic leukaemia) cells. Mitoxantrone dihydrochloride shows antitumor activity. Mitoxantrone dihydrochloride also has anti-orthopoxvirus activity with EC₅₀s of 0.25 μM and and 0.8 μM for cowpox and monkeypox, respectively.

Amantadine (1-Adamantanamine) is an orally avtive and potent antiviral agent with activity against influenza A viruses. Amantadine inhibits several ion channels such as NMDA and M2, and also inhibits Coronavirus ion channels. Amantadine also has anti-orthopoxvirus and anticancer activity. Amantadine can be used for Parkinson's disease, postoperative cognitive dysfunction (POCD) and COVID-19 research.

Trifluridine (Trifluorothymidine) is an irreversible and orally active thymidylate synthase inhibitor, and thereby suppressing DNA synthesis. Trifluridine is an antiviral molecule used for research of HSV, rhabdovirus and orthopoxvirus infection. Trifluridine induces cell apoptosis and autophagy. Trifluridine is also an anticancer agent used in studies of metastatic colorectal cancer, gastrointestinal tumors.

Tecovirimat (ST-246) is an orally bioavailable and selective compound against orthopoxviruses including vaccinia, monkeypox, camelpox, cowpox, ectromelia (mousepox), smallpox and variola viruses. Tecovirimat is evaluated against vaccinia, cowpox virus, ectromelia virus with EC₅₀ values of 0.01 μM, 0.48 μM and 0.05 μM, respectively. Tecovirimat targets the orthopoxvirus protein VP37 which is necessary for membrane envelopment of intracellular mature virus particles to form enveloped virus. Tecovirimat exerts antiviral activity on the target of the cowpox virus V061 gene, which is homologous to vaccinia virus F13L, encoding a major envelope protein (p37) required for production of extracellular virus.

Enrofloxacin (BAY Vp 2674) is an effective antibiotic with an MIC₉₀ of 0.312 μg/mL for Mycoplasma bovis.