nsP2 Protease Inhibitor Blocks the Replication of New World Alphaviruses and Offer Protection in Mice.

New World alphaviruses, including Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV), are mosquito-transmitted viruses that cause disease in humans. These viruses are endemic to the western hemisphere, and disease in humans may lead to encephalitis and long-term neurological sequelae. There are currently no FDA-approved vaccines or antiviral therapeutics available for the prevention or treatment of diseases caused by these viruses.

Host-Driven Ubiquitination Events in Vector-Transmitted RNA Virus Infections as Options for Broad-Spectrum Therapeutic Intervention Strategies.

Many vector-borne viruses are re-emerging as public health threats, yet our understanding of the virus-host interactions critical for productive infection remains limited. The ubiquitination of proteins, including host- and pathogen-derived proteins is a highly prominent and consistent post-translational modification that regulates protein function through signaling and degradation. Viral proteins are documented to hijack the host ubiquitination machinery to modulate multiple host processes including antiviral defense mechanisms.

Effects of N-glycan modifications on spike expression, virus infectivity, and neutralization sensitivity in ancestral compared to Omicron SARS-CoV-2 variants.

The SARS-CoV-2 spike glycoprotein has 22 potential N-linked glycosylation sites per monomer that are highly conserved among diverse variants, but how individual glycans affect virus entry and neutralization of Omicron variants has not been extensively characterized. Here we compared the effects of specific glycan deletions or modifications in the Omicron BA.1 and D614G spikes on spike expression, processing, and incorporation into pseudoviruses, as well as on virus infectivity and neutralization by therapeutic antibodies.

Interactions of Equine Viruses with the Host Kinase Machinery and Implications for One Health and Human Disease.

Zoonotic pathogens that are vector-transmitted have and continue to contribute to several emerging infections globally. In recent years, spillover events of such zoonotic pathogens have increased in frequency as a result of direct contact with livestock, wildlife, and urbanization, forcing animals from their natural habitats. Equines serve as reservoir hosts for vector-transmitted zoonotic viruses that are also capable of infecting humans and causing disease.

Inhibitors of the Ubiquitin-Mediated Signaling Pathway Exhibit Broad-Spectrum Antiviral Activities against New World Alphaviruses.

New World alphaviruses including Venezuelan Equine Encephalitis Virus (VEEV) and Eastern Equine Encephalitis Virus (EEEV) are mosquito-transmitted viruses that cause disease in humans and equines. There are currently no FDA-approved therapeutics or vaccines to treat or prevent exposure-associated encephalitic disease. The ubiquitin proteasome system (UPS)-associated signaling events are known to play an important role in the establishment of a productive infection for several acutely infectious viruses.

Characterization of Entry Pathways, Species-Specific Angiotensin-Converting Enzyme 2 Residues Determining Entry, and Antibody Neutralization Evasion of Omicron BA.1, BA.1.1, BA.2, and BA.3 Variants.

The SARS-CoV-2 Omicron variants were first detected in November 2021, and several Omicron lineages (BA.1, BA.2, BA.