Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3.

Enteroviruses cause a number of medically relevant and widespread human diseases with no approved antiviral therapies currently available. Host-directed therapies present an enticing option for this diverse genus of viruses. We have previously identified the actin histidine methyltransferase SETD3 as a critical host factor physically interacting with the viral protease 2A. Here, we report the 3.5 Å cryo-EM structure of SETD3 interacting with coxsackievirus B3 2A at two distinct interfaces, including the substrate-binding surface within the SET domain. Structure-function analysis revealed that mutations of key residues in the SET domain resulted in severely reduced binding to 2A and complete protection from enteroviral infection. Our findings provide insight into the molecular basis of the SETD3-2A interaction and a framework for the rational design of host-directed therapeutics against enteroviruses

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study

Functional foods as source of bioactive principles. Some marked examples

Functional foods are those that have a beneficial effect on health beyond the basic function of nutrition, helping to promote better health conditions and to reduce the risk of various diseases. This concept was created in Japan in the 1980s and is widely used around the world. The regulation of these products is made by different authorities and has not been defined yet in many countries. The field of food production has increased and changed considerably in the last decades, since the consumers believe that foods, besides satisfy hunger and to provide necessary nutrients for humans, also contribute directly to improve their health conditions. The present chapter will focus with marked examples the main categories of functional foods and respective therapeutic potential (cardioprotective, hepatoprotective, hypolipidemic, antioxidant, anticancer, anti-inflammatory properties, etc.) as well as the active principles responsible for the medicinal properties (flavonoids, alkaloids, terpenes, etc.), including curcuma, garlic, olive oil, grape, broccoli, and probiotic, among others

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

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