Orthornavirae

• Until the COVID-19 pandemic, however, vaccine development was still a long and idiosyncratic process.
• But the COVID-19 mRNA vaccines brought a new approach to vaccine development that has far-reaching implications for how researchers make drugs to treat many other diseases.

Some basics of mRNA drugs

• An mRNA drug comprises two essential components: mRNA molecules, which code for desired proteins, and the lipid molecules – such as phospholipids and cholesterol – that encapsulate them.
• From a drug development perspective, mRNA drugs offer significant advantages over traditional drugs because they are easily programmable.
• More importantly, different mRNA drugs produced by the same set of methods will have similar properties.
• This predictability significantly reduces the development risks and financial costs of developing mRNA drugs.

Self vs. nonself

• This may sound paradoxical – after all, your cells already contain large amounts of mRNAs.
• How does your immune system distinguish between self and nonself mRNAs?
• Therapeutic mRNAs enter cells using endosomes – sacs made of the cell’s membrane that take in materials from the cell’s environment.

• The 2023 Nobel Prize in physiology or medicine was awarded to the scientists who made this breakthrough discovery.
• RNA viruses also form double-stranded RNA when they replicate, and exposing cells to double-stranded RNA can lead to a strong immune response.
• Fortuitously, for mRNA vaccines, the residual amount of double-stranded RNA can stimulate the immune system to enhance antibody responses.

Moving beyond vaccines

• One promising example in development is using mRNA that encodes CRISPR-Cas9 gene-editing proteins to knock out genes that cause specific diseases.
• This disease is an ideal target for mRNA-based CRISPR gene therapy because the target protein is produced by the liver.

• Notable new developments in these areas include using computational algorithms to optimize mRNA sequences in ways that enhance their stability and engineering RNA polymerases that introduce fewer side products that may cause an immune response.
• Further advancements have the potential to enable a new generation of safe, durable and effective mRNA therapeutics for applications beyond vaccines.

Li Li receives funding from NIH.

• In the last decade, CHIKV has become a reemerging mosquito-transmitted virus that has spread into Europe, Asia, the Pacific Region, and the Americas, with epidemics causing severe economic impact.
• The programme is intended to position Emergex for entry to the clinic by its completion, ready to begin a Phase-1 clinical trial.
• Subsequently, Emergex achieved all milestones priming the CHIKV candidate for progression to the next stage of its preclinical development.
• A Phase-2 trial for CoronaTcP and a Phase-1 trial for a Universal Influenza vaccine candidate are planned in H1 2024.

• However, we don’t have a good understanding of the diversity of viruses circulating in bat populations in most parts of the world.
• We also don’t have a good idea of the number of bat viruses that could jump into humans in the future.
• This motivated new research, in which we searched for RNA viruses circulating in UK bats.

Studying UK bats

• These were mostly from injured or grounded bats rehabilitated by the Bat Conservation Trust.
• This strategy didn’t cause hurt or disturbance to any bat we sampled and didn’t increase contact rates between bats and humans.
• In the two species of British Rhinolophus bats we also found four sarbecoviruses, the same group of viruses as SARS-CoV-2.
• Our study likely underestimates the true diversity of coronaviruses circulating in UK bats since we sequenced only 48 samples and not all bats are infected by all viruses at all times.

Bats as reservoirs for zoonotic viruses

• Though, the large number of zoonotic viruses carried by bats may be primarily due to their high species diversity.
• So monitoring for viruses shouldn’t only focus on bats, but include other groups of mammals such as rodents, carnivores and ungulates (mammals with hooves).
• Read more:
  Why it's important to study coronaviruses in African bats

  It’s possible COVID was caused by a zoonotic pathogen, and it’s possible it wasn’t.

• But improved characterisation of pathogens with zoonotic potential would still allow preemptive design and testing of vaccines and drug compounds against the most threatening zoonotic pathogens.

• "This collaboration represents an exciting opportunity for Nona Biosciences to leverage its fully human antibody H2L2 transgenic mice, together with the technology and expertise in the development of innovative therapeutics," said Jingsong Wang, MD, PhD, Chairman of Nona Biosciences.
• "We believe that our collaboration with Dr. Michael S. Diamond's team will lead to breakthroughs in the field of viral therapeutics and ultimately improve patients' lives."
• Dr. Michael S. Diamond is a Professor of Medicine, Molecular Microbiology, Pathology & Immunology at Washington University School of Medicine.
• The Diamond laboratory is renowned for its research on molecular basis of disease of globally emerging RNA viruses and its focus on the interface between pathogenesis and host immunity.