Coronaviruses are causative agents of different zoonosis including SARS, MERS, or COVID-19 in humans. The high transmission rate of coronaviruses, the time-consuming development of efficient anti-infectives and vaccines, the possible evolutionary adaptation of the virus to conventional vaccines, and the challenge to cover broad human population worldwide are the major reasons that made it challenging to avoid coronaviruses outbreaks. Although, a plethora of different approaches are being followed to design and develop vaccines against coronaviruses, most of them target subunits, full-length single, or only a very limited number of proteins. Vaccine targeting multiple proteins or even the entire proteome of the coronavirus is yet to come. In the present chapter, we will be discussing multi-epitope vaccine (MEV) and multi-patch vaccine (MPV) approaches to design and develop efficient and sustainably successful strategies against coronaviruses. MEV and MPV utilize highly conserved, potentially immunogenic epitopes and antigenic patches, respectively, and hence they have the potential to target large number of coronavirus proteins or even its entire proteome, allowing us to combat the challenge of its evolutionary adaptation. In addition, the large number of human leukocyte antigen (HLA) alleles targeted by the chosen specific epitopes enables MEV and MPV to cover broader global population.
The identification and characterization of enzyme function is lacking behind the rapidly increasing availability of large numbers of sequences and associated high-resolution structures. This often hampered by lack of knowledge on in vivo relevant substrates. Here, we present a case study where the high-resolution structure of an unusual orphan lipase in complex with an endogenous C18 monoacyl catalysis intermediate allowed its functional characterization as long-chain monacylglycerol lipase. Different from most other lipases, this enzyme uses a minimal helix-β-hairpin-helix lid domain that positions the substrate through a hydrophobic tunnel directly to the enzyme's active site. Knowledge about the molecular details of the substrate binding site and hydrolysis allowed us to boost the enzymatic activity by adjusting protein/substrate interactions. This enzyme serves as a prototype for non-conventional esterases and lipases that share similar helix-β-hairpin-helix lid domains of variable size. Taken together, our data provide crucial insight to advance our knowledge of unusual esterases and lipases, facilitating future biotechnology
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