Exploring G protein-coupled receptors and yeast surface display strategies for viral detection in baker's yeast: SARS-CoV-2 as a case study

Abstract

Viral infections pose intense burdens to healthcare systems and global economies. The correct diagnosis of viral diseases represents a crucial step towards effective treatments and control. Biosensors have been successfully implemented as accessible and accurate detection tests for some of the most important viruses. While most biosensors are based on physical or chemical interactions of cell-free components, the complexity of living microorganisms holds a poorly explored potential for viral detection in the face of the advances of synthetic biology. Indeed, cell-based biosensors have been praised for their versatility and economic attractiveness, however, yeast platforms for viral disease diagnostics are still limited to indirect antibody recognition. Here we propose a novel strategy for viral detection in Saccharomyces cerevisiae, which combines the transductive properties of G Protein-Coupled Receptors (GPCRs) with the Yeast Surface Display (YSD) of specific enzymes enrolled in the viral recognition process. The GPCR/YSD complex might allow for active virus detection through a modulated signal activated by a GPCR agonist, whose concentration correlates to the viral titer. Additionally, we explore this methodology in a case study for the detection of highly pathogenic coronaviruses that share the same cell receptor upon infection (i.e. the Angiotensin-Converting Enzyme 2, ACE2), as a conceptual example of the potential of the GPCR/YSD strategy for the diagnosis of COVID-19.

Effect of a Nutritional Support System to Increase Survival and Reduce Mortality in Patients with COVID-19 in Stage III and Comorbidities: A Blinded Randomized Controlled Clinical Trial

“…One of the components of NSS is inulin. The positive effects of dietary fiber and inulin are known to promote the production of SCFAs by fermentation in the intestine and together with omega-3 PUFAs regulate TNF-alpha which is directly related to the inflammatory cascade and cachexia, two physiological processes related to mortality in patients with COVID-19 [27], especially in overweight, obese, and DM2 patients (Birkeland and Van der Beek) [60,61].…”

“…Consumption of inulin-type fructans has been associated with regulation of the immune system, modulation of GI peptides, production of SCFA and modulation of triglyceride metabolism. SCFA are a source of energy for colonocytes, stimulating the synthesis of IL-10 by macrophages, neutrophils and T cells, as well as inhibiting the synthesis of TNF-α and IL-6 [27].…”

“…The balance of proteins of high biological value (PHBV) increases antibody production, modulates inflammatory response, stimulates GALT, MALT, and BALT [27]. Brewer's yeast provides Saccharomyces cerevisiae (SC) and has an immunomodulatory effect by stimulating GPCR/YSD, prevents ACE2 receptor binding to SARS-CoV-2 protein S, and modulates the activation of MAPKs, inhibiting the production of IL-1β, IL-6, and TNF-α [26].…”

Yeast Surface Display System: Strategies for Improvement and Biotechnological Applications

“…Recent advances in human health care include a vaccine against candidiasis ( Shibasaki et al, 2013 ; Ueda, 2016 ) and a platform to detect SARS-CoV-2 ( Maneira et al, 2021 ). Animal vaccines have been developed which include vaccines against Toxoplasma gondii ( Wang et al, 2018 ), a vaccine against hemorrhagic disease of grass carp ( Luo et al, 2015 ) and an anti-tick vaccine ( Trentelman et al, 2021 ).…”