Current COVID-19 vaccines need to take at least one month to complete inoculation and then become effective. Around 51% of the global population is still not fully vaccinated. Instantaneous protection is an unmet need among those who are not fully vaccinated. In addition, breakthrough infections caused by SARS-CoV-2 are widely reported. All these highlight the unmet needing for short-term instantaneous prophylaxis (STIP) in the communities where SARS-CoV-2 is circulating. Previously, we reported nanobodies isolated from an alpaca immunized with the spike protein, exhibiting ultrahigh potency against SARS-CoV-2 and its variants. Herein, we found that Nb22, among our previously reported nanobodies, exhibited ultrapotent neutralization against Delta variant with an IC50 value of 0.41 ng/ml (5.13 pM). Furthermore, the crystal structural analysis revealed that the binding of Nb22 to WH01 and Delta RBDs both effectively blocked the binding of RBD to hACE2. Additionally, intranasal Nb22 exhibited protection against SARS-CoV-2 Delta variant in the post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Of note, intranasal Nb22 also demonstrated high efficacy against SARS-CoV-2 Delta variant in STIP for seven days administered by single dose and exhibited long-lasting retention in the respiratory system for at least one month administered by four doses, providing a strategy of instantaneous short-term prophylaxis against SARS-CoV-2. Thus, ultrahigh potency, long-lasting retention in the respiratory system and stability at room-temperature make the intranasal or inhaled Nb22 to be a potential therapeutic or STIP agent against SARS-CoV-2.

Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule (QHJTC) in the treatment of type 2 diabetes mellitus (T2DM) through network pharmacology and molecular docking. Methods The active components of materia medica in the formula of QHJTC were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine. The targets related to the active components were obtained via PubChem database. The targets related to T2DM were retrieved through the GeneCards database. The targets corresponding to the active components and diabetes mellitus were uploaded to the Venn diagrams website to get the Venn diagram, and the intersecting targets were the potential targets of QHJTC in treating T2DM. The active components and potential targets were imported into Cytoscape 3.7.2 software to construct the active component–potential target network, and the key compounds and targets were screened by the Network Analyzer module in the Tools module. The potential targets were imported into the STRING database to obtain the interaction relationships, so as to analyze and construct the protein–protein interaction (PPI) network by Cytoscape 3.7.2 software. The intersecting targets were introduced into Metascape for gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The top 20 signaling pathways obtained by the KEGG pathway enrichment analysis and the related targets and the corresponding targets were analyzed by using Cytoscape 3.7.2 software to construct the “active component–important target-key pathway network ” for the intervention of T2DM with QHJTC. The molecular docking of active components and core targets was performed with AutoDock software. Results A total of 237 active components and 281 related targets were obtained from QHJTC, as well as 1 362 T2DM targets and 155 potential targets of QHJTC in treating T2DM. There were 32 key components and 49 key targets identified by the active component–potential target network topology analysis. There were 471 terms obtained from GO functional enrichment analysis, among which 248 related to biological processes, 125 related to molecular functions, and 98 related to cellular components. There were 299 signaling pathways obtained from KEGG pathway enrichment analysis. The active components of QHJTC were found spontaneously binding to the core targets. Conclusions QHJTC can treat T2DM through multi-components, multi-targets, and multi-pathways.