A human monoclonal antibody potently pan-neutralizes SARS-CoV-2 VOCs by targeting RBD invariant sites (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

Isolation and characterization of a porcine epidemic diarrhea virus strain Jiaozuo1012/2019

In order to determine the causative agent of diarrhea of suckling piglets in a pig farm in Jiaozuo city in 2019, RTPCR was used to detect the related viral pathogens from five clinical samples. The results showed that all five samples were positive for PEDV, but negative for TGEV and PoRV. A PEDV strain named as Jiaozuo1012/2019 was isolated from the positive samples by using Vero cells through detecting the fifth passaged virus by RT-PCR. The S gene and ORF3 gene of the isolated PEDV were amplified by RT-PCR, and the homology and phylogenetic tree of these two genes were analyzed by compared with PEDV reference strain in GenBank. Based on the homology analysis of S gene and ORF3 gene, S gene of this isolated PEDV had the highest homology (99.3%) with PEDV CH/HNLH/2015 strain isolated in Henan province. The homology of S gene of PEDV Jiaozuo1012/2019 strain with other strains isolated in Henan province was 96.4%-99.0%. The homology of S gene of this isolated virus with the classic PEDV CV777 strain was 93.4%, and there are 4 insertions (59QGVN62) and 3 deletions (140N and 163NI164) in S protein of this isolated virus. The ORF3 gene shared 99.7% homology with PEDV JSCZ1601 strain isolated in Jiangsu province, among 96.4%-99.0% homology with other strains isolated in Henan province, and 96.6% homology with classical PEDV CV777 strain. The phylogenetic tree analysis of S gene and ORF3 gene showed that the isolated virus had the closest genetic relationship with the current domestically epidemic strains. This study provides reference data for further studying the variation of PEDV in Henan province.

Human H-ferritin presenting RBM of spike glycoprotein as potential vaccine of SARS-CoV-2 (preprint)

The outbreak of COVID-19 has so far inflicted millions of people all around the world and will have a long lasting effect on every aspect of everyones life. Yet there is no effective approved treatment for the disease. In an effort of utilizing human ferritin as nanoplatform for drug delivery, we engineered a fusion protein by presenting receptor-binding motif (RBM) of SARS-CoV-2 virus spike glycoprotein on the N-terminus of ferritin subunits. The designed fusion protein with a cage-like structure, similar to that of corona virus, is a potential anti-SARS-CoV-2 vaccine. We hereby show the construction, preparation, and characterization of the fusion protein RBM-HFtn. Our initial affinity study confirmed its biological activity towards ACE2 receptor which suggests its mode of action against SARS-CoV-2 could be either through vaccine therapy or blocking the cellular entry of virus as antagonist of ACE2 receptor.