ENZYMES, GROWTH FACTORS, PROTEINS, AND RECEPTORS

Viral polyproteins

Cleaved by MPRO (viral protease) during viral replication

MPRO (viral protease)

An enzyme essential in HIV replication that cleaves two viral polyproteins; inhibited by Nirmatrelvir

CYP3A4

Inhibited by Ritonavir to increase the half-life and bioavailability of Nirmatrelvir

Viral RNA-dependent RNA polymerases

Enzymes that uptake beta-D-N4-hydroxycytidine (NHC), resulting in mutations and lethal mutagenesis

Janus kinase (JAK)

Inhibited by Baricitinib, used for hospitalized COVID-19 patients

Interleukin-6 receptor antagonist

Tocilizumab is a recombinant humanized antagonist of this receptor, used for hospitalized COVID-19 patients

IL-1 receptor antagonist

Anakinra is a recombinant antagonist of this receptor, used for hospitalized COVID-19 patients

Anti-C5a monoclonal antibody

Vilobelimab is this type of molecule, used for hospitalized adults requiring mechanical ventilation or ECMO

Viral p37

Inhibited by Tecovirimat (TPOXX), blocking viral release from infected cells

Lectin-like molecule

Used by Plasmodium merozoites to bind to sialic acid residues on glycophorin molecules on the red cell surface to invade RBCs

Sialic acid residues

Located on glycophorin molecules on the red cell surface, bound by a lectin-like molecule used by Plasmodium merozoites

Glycophorin molecules

Contain sialic acid residues on the red cell surface, bound by Plasmodium merozoites

Hgb (Hemoglobin)

Hydrolyzed by enzymes produced by the Plasmodium parasite growing in RBCs

P falciparum erythrocyte membrane protein-1 (PfEMP1)

Forms knobs on RBC surfaces, binding to ligands on endothelial cells and causing RBC sequestration in cerebral malaria

GPI-linked proteins

Including merozoite surface antigens, these are released from infected red cells and induce cytokine production, increasing fever

Merozoite surface antigens

A type of GPI-linked protein released from infected red cells that induces cytokine production

Glycoproteins (Leishmania promastigotes)

Molecules produced to manipulate host defenses to facilitate survival in the macrophage

Lipophosphoglycan

A glycoprotein produced by Leishmania promastigotes that interferes with the complement pathway

Gp63

A zinc-dependent proteinase produced by Leishmania promastigotes that cleaves critical host enzymes

Endonucleases

Enzymes formed by Leishmania to resist neutrophil extracellular trap formation

Proton-transporting ATPase

Secreted by Leishmania to maintain phagolysosome pH at 6.5

Iron transporter (from ZIP family of membrane proteins)

Used by Leishmania amastigotes for iron entry into phagolysosomes

MicroRNAs

Used by Leishmania to regulate gene expression to affect cellular signaling and disrupt immunity

Variant surface glycoprotein (VSG)

A single, abundant, glycolipid-anchored protein that covers Trypanosomes and undergoes genetic rearrangement to escape immune response

Glycoproteins (surface of T. cruzi)

Family of molecules used by Trypanosoma cruzi to interact with multiple ligands to facilitate cell adhesion and invasion into macrophages

Pore-forming proteins

Activated by trypomastigotes elevating cytoplasmic calcium, these disrupt the lysosomal membrane to release the parasite into the cytoplasm

Taeniaestatin

Produced by Taenia solium cysts to inhibit complement activation and evade host defenses

Paramyosin

Produced by Taenia solium cysts to inhibit complement activation and evade host defenses

Tyvelose

Larval antigen antibodies that are useful for serodiagnosis of Trichinella spiralis

IL-4 (Interleukin 4)

Stimulates TH2 response in Trichinella spiralis infection

IL-5 (Interleukin 5)

Stimulates TH2 response in Trichinella spiralis infection, activating eosinophils and mast cells

IL10 (Interleukin 10)

Stimulates TH2 response in Trichinella spiralis infection

IL-13 (Interleukin 13)

Stimulates TH2 response in Trichinella spiralis infection

Proteolytic enzyme

Powerful molecule used by Schistosoma cercariae to degrade the keratinized layer of human skin to penetrate

Elastase

Filarial molecule that facilitates invasion of host tissues

Trypsin-like proteases

Filarial molecule that facilitates invasion of host tissues

Surface glycoproteins (filarial)

Have antioxidant function and protect the parasite from reactive oxygen species (ROS)

Cystatin homologues

Filarial molecules that impair MHC class II antigen-processing pathway

Serpins

Filarial molecules that inhibit neutrophil proteases

TGF-B (Transforming Growth Factor Beta)

A host molecular homologue used by filarial parasites to dampen the immune response

Macrophage inhibition factor

A host molecular homologue used by filarial parasites to dampen the immune response

β-tubulin dimers

Bound to and disrupted by Benzimidazoles, preventing microtubule assembly in helminths

Microtubule

Cellular structure whose assembly in intestinal and tegmental cells of helminths is prevented by Benzimidazoles

Fumarate reductase

A parasitic-specific enzyme inhibited by Benzimidazoles/Triclabendazole, leading to decreased levels of NADH and energy depletion

Acetylcholine

Released by Pyrantel Pamoate (a depolarizing neuromuscular blocking agent) and blocked at the myoneural junction by Piperazine

Cholinesterase

Enzyme inhibited by Pyrantel Pamoate and Metrifonate (Trichlorfon)

Glutamate-gated Cl- channels

Intensification of neurotransmission through these channels is caused by Ivermectin, leading to paralysis

GABA-mediated neurotransmission

Intensified by Ivermectin, leading to paralysis

Ivermectin

Binds selectively and with high affinity to glutamate-gated chloride channels, enhancing the channel so more chloride ions enter

30s ribosomal subunit

Inhibited by Doxycycline and Paromomycin (aminoglycoside)

Calcium

Increased permeability of cestode/trematode cell membranes to this ion is the mechanism of action of Praziquantel, leading to paralysis

Oxidative phosphorylation inhibitor

Niclosamide is described as this type of molecule, which interferes with ATP production

ATPase stimulator

Niclosamide is described as this type of molecule

DNA synthesis inhibitor

Metronidazole and Tinidazole are categorized as this type of molecule, causing loss of helical DNA structure and strand breakage

40s ribosomal subunit

Bound to by Emetine, decreasing ribosome-RNA interaction and reducing protozoal protein synthesis

Adrenergic transmission

Blocked by Emetine in humans, contributing to its side effects

Cholinergic transmission

Blocked by Emetine in humans, contributing to its side effects

Nitroreductase enzyme

Reduces the nitro group of Tinidazole to an unstable, cytotoxic intermediate

Pyruvate: ferredoxin oxidoreductase pathway

Inhibited by Tizoxanide (active metabolite of Nitazoxanide) in anaerobic bacteria

Bacterial enzymes

Interfered with by Furazolidone (active metabolite: Nitrofuran)

gp160 (glycoprotein)

Viral envelope glycoprotein complex consisting of gp120 and gp41 that binds to its cellular receptor CD4+ T cell

CD4+ T cell

Cellular receptor complex to which the viral envelope glycoprotein complex gp160 binds during HIV entry

gp120

Component of gp160; binding to CD4+ T cell induces conformational changes in this molecule, enabling access to chemokine receptors

CCR5

Chemokine receptor that gp120 enables access to; Maraviroc selectively binds to this host protein

CXCR4

Chemokine receptor that gp120 enables access to after binding to CD4+ T cell

gp41

Component of gp160 that leads to fusion of viral envelope with host cell membrane; Enfuvirtide binds to this subunit

HIV-1 reverse transcriptase

Enzyme competitively inhibited by NRTIs, leading to premature viral DNA chain termination

Mitochondrial DNA polymerase gamma

Inhibition of this enzyme is the likely cause of NRTI hallmark mitochondrial toxicity

p66

NNRTIs bind to a hydrophobic pocket in the palm subdomain of this molecule in HIV-1 reverse transcriptase, causing allosteric inhibition

Allosteric inhibition

Mechanism of action of NNRTIs on RNA-dependent and DNA-dependent DNA polymerase activity

CYP3A4

Enzyme system for which all NNRTIs are substrates; also extensively metabolizes all PIs

Inducers

Nevirapine acts as this type of modulator for CYP450 enzymes

Inhibitors

Delavirdine acts as this type of modulator for CYP450 enzymes

Mixed inducers and inhibitors

Efavirenz and Etravirine act as this type of modulator for CYP450 enzymes

CYP3A and CYP2D6 enzymes

Enzymes that extensively metabolize Delavirdine

CYP3A4 and CYP2B6

Enzymes that principally metabolize Efavirenz to inactivate hydroxylated metabolites

CYP3A4

Etravirine is a substrate and inducer of this enzyme

CYP2C9 and CYP2C19

Etravirine is an inhibitor of these enzymes

CYP3A isoform

Enzyme isoform that extensively metabolizes Nevirapine to hydroxylated metabolites

gag-pol polyprotein

Its post-translational cleavage is prevented by PIs, resulting in immature, non-infectious viral particles

HIV protease

Enzyme responsible for cleaving polyproteins to produce the final structural proteins of the mature virion core; inhibited by PIs

UGT1A1 glucuronidation enzyme

Inhibition of this enzyme by Atazanavir or Indinavir causes unconjugated hyperbilirubinemia

Ritonavir

Inhibits the CYP3A-mediated metabolism of Lopinavir, leading to increased Lopinavir exposure

CYP3A and CYP2D6 isoforms

Enzymes that metabolize Ritonavir to an active metabolite

P-glycoprotein

Maraviroc is a substrate for this molecule, which limits intracellular concentrations of the drug

Integrase

Viral enzyme essential to replication of HIV-1 and HIV-2 that is bound by ISTIs

Cobicistat

A pharmacokinetic enhancer that inhibits CYP3A4, required to boost Elvitegravir

UGT1A1

Primary enzyme responsible for the metabolism of Dolutegravir (primarily) and Raltegravir (by glucuronidation)

Monoclonal antibodies

Palivizumab and Nirsevimab are this type of molecule, licensed for prevention of RSV

Glycoprotein G

RSV envelope protein responsible for viral attachment to the cell and assisting the virus in evading host immunity

Fusion protein F

RSV envelope protein responsible for viral penetration of the epithelial cell after viral attachment, and a conserved target for vaccine and monoclonal antibody development

Small hydrophobic protein SH

One of the 3 surface glycoproteins on the RSV envelope

T-lymphocytes

Preferentially infected by Human Herpesvirus 6 and 7 (Roseolovirus)

Viral homologues of cellular genes

What herpes virus genes encode a lot of enzymes that appear as

Viral DNA

Detected by PCR in replicating viruses (not latent infection) for Cytomegalovirus

Viral DNA polymerase

Inhibited by ganciclovir, and whose alteration can lead to resistance to acyclovir in HSV/VZV

Viral thymidine kinase

Alteration in this enzyme can lead to resistance to acyclovir in HSV/VZV

DNA polymerase

Inhibited directly by foscarnet (phosphonoformic acid)

RNA polymerase

Inhibited directly by foscarnet (phosphonoformic acid)

HIV reverse transcriptase

Inhibited directly by foscarnet (phosphonoformic acid)