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Proof of concept is provided for the use of codon deoptimization (CD) as a rational strategy to generate attenuated RVFV, for the development of next-generation vaccines against this zoonotic threat.
The results demonstrate the feasibility of using rBA.5 ZsG-Nluc to track viral infections and identify prophylactics and therapeutics against recent SARS-CoV-2 VoCs in vitro, ex vivo, and in vivo.
This work indicates that SARS-CoV-2 can tolerate substantial impairment of proofreading but only when residual exonuclease activity remains above a minimal threshold, and defines this activity threshold to help guide antiviral strategies that target coronavirus proofreading.
The synergistic relationship between nsp15 and ORF6 is essential for efficient SARS-CoV-2 replication and it is hypothesized that since nsp15 functions by reducing dsRNA upstream of ORF6, nsp15 acts as a more potent antagonist leaving little activity for ORF6 to account for.
The reduced pathogenicity of rSARS-CoV-2 Nsp1 mutants highlights the potential for targeting Nsp1 for rational design of viral inhibitors and development of live-attenuated vaccine strategies as effective prophylactic and therapeutic treatments to combat SARS-CoV-2 and possibly other CoV infections.
Current evidence on cross-reactive and cross-protective immunity to H5N1 in humans, focusing primarily on humoral immune responses is summarized, and particular attention is given to antibodies targeting conserved regions of hemagglutinin (HA) as well as neuraminidase (NA), which may provide heterosubtypic protection.
A genome engineering technology is used to change a single amino acid in the viruses’ main protease enzyme to match that of circulating Omicron isolates to demonstrate antiviral efficacy of approved drugs and uncover mutants with reduced drug sensitivity.
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