Directed evolution
to combat emerging pathogens

(A) Antibody engineering and evolution to target emerging zoonotic pathogens:

 

Our adaptive  immune system evolves antibodies in real time to combat threats associated with invading pathogens. Inspired by how our adaptive immune system evolves antibodies, we are developing novel laboratory evolution platforms for evolving antibodies targeting emerging zoonotic pathogens. Such antibody evolution approaches are expected to provide a platform for evolving human antibodies targeting epitopes on viruses, drug resistant bacteria and cancer. To identify new starting points for antibody evolution, we are also developing single B cell sequencing approaches to obtain antibody sequences from zoonotic hosts reservoirs. Our studies could inform biologics development, vaccine design and diagnostics.

 

(B) Targeting RNA capping enzymes from emerging pathogenic RNA viruses:

 

It has become imperative to develop novel therapeutics to tackle emerging zoonotic RNA and DNA viruses. ​​​​In order to develop novel strategies to combat these viruses, we are targeting an essential but relatively less explored targets in viral replication, translation and propagation, i.e., viral genome encoded RNA capping enzymes. During the course of evolution, most of the viruses evolved mechanisms to incorporate an RNA cap structure that is chemically identical to the host mRNAs; essentially viruses mimic their genomes or transcripts as host mRNAs. These viral RNA cap structures are necessary for viral replication, translation and immune evasion.

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We are developing synthetic biology approaches to understand the molecular details of these essential viral enzymes. Further we are using a directed evolution to target these enzymes to systematically engineer attenuated variants and study the implication of these attenuated variants on viral pathogenesis. We are also using medicinal chemistry approaches to develop novel antivirals selectively targeting viral RNA capping enzymes over human RNA capping enzymes. We are expanding these approaches to combat human and animal viruses from a point of view of being better prepared for the next viral pandemic.

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