Ubiquitin Variants as Antiviral Agents
Emerging viruses pose a tremendous challenge to human health. Recent Middle East respiratory syndrome coronavirus (MERS-CoV) virus emergence and a subsequent array of reported human cases, or which 35% are lethal, exemplify the continued threat or (re) emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. MERS-CoV and the Crimean-Congo hemorrhagic fever virus (another re-emerging lethal virus causing increasing problems) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity which makes them highly attractive antiviral drug targets. The fact that these and other viruses bind the cellular protein ubiquitin can now be used as a basis for development or a highly innovative antiviral strategy.
Besides vaccines, which are arguably the most desirable remedies against virus infections, specific antiviral drugs are of pivotal importance. Especially for re-emerging virus infections such as those causing MERS and CCHF in acute outbreak situations these drugs provide immediate treatment options for infected patients and prophylactic medicine for people at acute risk of infection, such as medical personnel and close relatives. The standard approach is to use generic antivirals (ribavirin) or general immune boosters (interferon) or look for small chemical compounds that target viral or host enzymes. All of these are often ineffective and have major side-effects. This proof-of-principle work now shows that structurally diverse, virus-specific deubiquitinating enzymes can be selectively targeted with very high affinity binders based on the natural ligand ubiquitin itself, which opens new avenues for quickly developed molecularly tailored therapy across a broad spectrum of viral pathogens that infect humans, livestock and plants. PLoS Pathog 13 (5): e1006372).
Luris reference numberES180727-3777-8580
Patent application submitted PCT / NL2018 / 050137.