Highlights d RBD and HR nanoparticle vaccines induce potent neutralizing antibody responses d Nanoparticle vaccines protect against SARS-CoV-2 infection in mice d HR antigens elicit both humoral and cellular immune responses d HR antigens within nanoparticles contribute to crossprotective immunity

Zika virus (ZIKV) is genetically and biologically related to other Flaviviridae family members and has disseminated to many countries. It is associated with severe consequences including the abnormal development of the neural system in fetuses and neurological diseases in adults. Therefore, developing anti-ZIKV drugs is of paramount importance. Screening of generic drugs revealed that several non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen, naproxen, acetaminophen, and lornoxicam potently inhibit the entry of Zika-Env/HIV-1 pseudotyped viruses. They also significantly inhibited the replication of wildtype ZIKV, both in cell lines and in primary human fetal endothelial cells. Interestingly, NSAIDs exerted this inhibitory effect by potently reducing the expression of AXL, the entry cofactor of ZIKV. Further studies showed that NSAIDs down-regulated the PGE2/EP/cAMP/PKA signaling pathway, and reduced PKA-dependent CDC37 phosphorylation and the interaction between CDC37 and HSP90, which subsequently facilitated the CHIP/ubiquitination/proteasome-mediated AXL degradation. Taken together, our results highlight a new mechanism of action of antiviral agents, which may assist in designing a convenient strategy for treating ZIKV-infected patients. Zika virus (ZIKV) infection, which causes congenital malformations, including microcephaly and other neurological disorders, has attracted global attention. We observed that several NSAIDs significantly inhibited ZIKV infection. Based on our observations, we proposed a novel mechanism of action of antiviral compounds, which involves blockade of virus entry via degradation of the entry cofactor. Furthermore, NSAIDs can be practically used for preventing ZIKV infection in pregnant women, as certain NSAIDs, including ibuprofen and acetaminophen, are considered clinically safe.

HIV‐1 latency is a major obstacle to achieving a functional cure for AIDS. Reactivation of HIV‐1‐infected cells followed by their elimination via immune surveillance is one proposed strategy for eradicating the viral reservoir. However, current latency‐reversing agents (LRAs) show high toxicity and low efficiency, and new targets are needed to develop more promising LRAs. Here, we found that the histone chaperone CAF‐1 (chromatin assembly factor 1) is enriched on the HIV‐1 long terminal repeat (LTR) and forms nuclear bodies with liquid–liquid phase separation (LLPS) properties. CAF‐1 recruits epigenetic modifiers and histone chaperones to the nuclear bodies to establish and maintain HIV‐1 latency in different latency models and primary CD4+ T cells. Three disordered regions of the CHAF1A subunit are important for phase‐separated CAF‐1 nuclear body formation and play a key role in maintaining HIV‐1 latency. Disruption of phase‐separated CAF‐1 bodies could be a potential strategy to reactivate latent HIV‐1.

No abstract