7x7d

From Proteopedia

SARS-CoV-2 Delta RBD and Nb22

Structural highlights

7x7d is a 6 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2 and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.92Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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 IC(50) 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.

Short-Term Instantaneous Prophylaxis and Efficient Treatment Against SARS-CoV-2 in hACE2 Mice Conferred by an Intranasal Nanobody (Nb22).,Wu X, Wang Y, Cheng L, Ni F, Zhu L, Ma S, Huang B, Ji M, Hu H, Li Y, Xu S, Shi H, Zhang D, Liu L, Nawaz W, Hu Q, Ye S, Liu Y, Wu Z Front Immunol. 2022 Mar 17;13:865401. doi: 10.3389/fimmu.2022.865401. eCollection , 2022. PMID:35371009^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu X, Wang Y, Cheng L, Ni F, Zhu L, Ma S, Huang B, Ji M, Hu H, Li Y, Xu S, Shi H, Zhang D, Liu L, Nawaz W, Hu Q, Ye S, Liu Y, Wu Z. Short-Term Instantaneous Prophylaxis and Efficient Treatment Against SARS-CoV-2 in hACE2 Mice Conferred by an Intranasal Nanobody (Nb22). Front Immunol. 2022 Mar 17;13:865401. doi: 10.3389/fimmu.2022.865401. eCollection, 2022. PMID:35371009 doi:http://dx.doi.org/10.3389/fimmu.2022.865401